research paper on the 1980s

HIST 4337 The 1980s: Politics, Culture, and Memory in the United States

HIST 4337 The 1980s: Politics, Culture, and Memory in the United States (also AMST 4337)(ALC-AS, HST-AS) (HNA)

Tuesday: 2:00-4:30 plus Independent Research

Professor Stephen Vider

This seminar will examine U.S. culture and politics in the 1980s as a pivotal decade in shaping our contemporary cultural, social, and political landscape. We will consider how U.S. culture and politics shifted with the "Reagan Revolution" and the end of the Cold War, and their connections to and ramifications for social activism, social welfare, media, foreign policy, and everyday life. At the same time, we will consider the methodological opportunities and challenges in researching, writing, reading, and presenting recent history. Students will complete a research paper, and work together to design and launch a digital exhibition on the 1980s. We will also explore how 1980s culture and politics was shaped by nostalgia for the 1950s, and how the 1980s and remembered and misremembered today. Topics include the rise of neoliberalism, privatization of civil and social services, the emergence of digital technologies, activism in response to HIV/AIDS, transnational feminisms, the consolidation of the Christian right, and the “Culture Wars.” Readings will include historical scholarship, as well as creative non-fiction, films, TV, and music from the 1980s.

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Iconic Moments of The 1980s: Introduction

• Introduction

This guide will connect Gumberg Library users to resources pertaining to the essential figures and events of the 1980s. From pop culture trendsetters to military conflicts and political figureheads, this guide aims to display the vital moments and people who contributed to this decade's history. This resource will link you to reference works for background information and basic facts, print books and ebooks, and databases for articles from magazines, newspapers, and journals.

Intro Picture

A collage of intellectual properties that were popular and/or created in the 1980s

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This research guide was created by Thomas DeMauro III, English Department Intern, Gumberg Library, March 2022

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• Last Updated: Oct 30, 2023 4:08 PM
• URL: https://guides.library.duq.edu/1980s

American Economic Policy in the 1980s: A Personal View

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Articles on 1980s

Displaying 1 - 20 of 23 articles.

This Town: new drama charts the influence of ska on inner city kids during bleak Thatcher years

Adam Behr , Newcastle University

Kiss’s debut album at 50: how the rock legends went from ‘clowns’ to becoming immortalised

Charlotte Markowitsch , RMIT University

All of Us Strangers: coming to terms with the grief and trauma of being gay in the 1980s

Cüneyt Çakırlar , Nottingham Trent University

I’ve rewatched 150 episodes of Brookside – here’s how the soap captured the nuances of Margaret Thatcher’s Britain

Ben Williams , University of Salford

The World Bank used to cause untold harm – but 30 years ago it started reforming. What went right

Danny Bradlow , University of Pretoria

Rap artists have penned plenty of lyrics about US presidents – this course examines what they say about Reagan and the 1980s

Stefan M. Bradley , Amherst College

Controlling monkeypox: The time for Canada to act is now

Kevin Woodward , McMaster University

It’s not nostalgia. Stranger Things is fuelling a pseudo-nostalgia of the 1980s

Tom van Laer , University of Sydney and Davide Christian Orazi , Monash University

Sexism, big hair, contact books: The Newsreader gets a lot right about 80s TV journalism but the times were not so diverse

Helen Vatsikopoulos , University of Technology Sydney

Halston: The glittering rise – and spectacular fall – of a fashion icon

Jennifer Gordon , Iowa State University and Sara Marcketti , Iowa State University

Giant ‘toothed’ birds flew over Antarctica 40 million to 50 million years ago

Peter A. Kloess , University of California, Berkeley

How 80s TV show MacGyver is inspiring doctors during the coronavirus pandemic

Stuart Marshall , Monash University

It’s hot in here: the evolution of Goth subculture in sub-tropical Brisbane

Sebastien Darchen , The University of Queensland and John Willsteed , Queensland University of Technology

Only Fools and Horses, Charles Dickens and the precariat, then and now

David Amigoni , Keele University

Brett Kavanaugh goes to the movies

Marsha Gordon , North Carolina State University

Dreams in an Empty City: a strikingly prescient morality tale about banking

Julian Meyrick , Flinders University

‘We are women, we are strong’: celebrating the unsung heroines of the miners’ strike

Patricia Francis , Nottingham Trent University

Stranger Things 2 is darker and weirder, tempered with grief

Mark Steven , UNSW Sydney

Stranger Things: inventiveness in the age of the Netflix original

Arin Keeble , Edinburgh Napier University

Why pop needs its eccentric characters

Mark Goodall , University of Bradford

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Senior Lecturer in Planning, The University of Queensland

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Five Pop Culture Trends That Helped Shape the 1980s

By: Lesley Kennedy

Updated: October 2, 2023 | Original: February 25, 2022

American popular culture in the 1980s reflected larger social, political, technological and media trends, from the rapid spread of cable television to the cultural peak of suburban malls. Here’s a look at five pop culture trends that heavily shaped the “Me” decade.

Women’s Power Dressing

Shoulder pads. Oversized double-breasted suits. The floppy silk “tie.” On runways and movie sets, in office buildings and boardrooms, women of the ’80s dressed in masculine-inspired fashions to express their growing power. Corporate business women, First Lady Nancy Reagan and global icon Princess Diana  alike embraced the suit look, as did heavy-hitting designers of the era including Giorgio Armani, Thierry Mugler and Calvin Klein. The suits, shoulder pads and lady ties permeated pop culture as well, showcased in movies such as 9 to 5 (1980) and  Working Girl (1988) and TV shows like Dynasty (1981-89) and  Moonlighting (1985-89)—all of which featured strong female characters who brought even more popularity to the power dressing trend.

All this came during a decade when women’s participation in the labor force steeply increased, according to the U.S. Bureau of Labor Statistics , and when Americans watched glass ceilings shatter across the professional spectrum. In 1981, judge Sandra Day O'Connor began her appointment as the first woman on the Supreme Court. Three years later, U.S. Representative Geraldine Ferraro became the first woman vice-presidential candidate for a major party and Sally Ride was America's first woman in space. And Oprah Winfrey, in 1986, became the first woman to produce and own her own talk show, encouraging other women to stand on her well-padded shoulders.

Food + Fun = ‘Eatertainment’ 

Video games saw a huge rise in the 1980s, with standup machines like “Centipede” and, “Pac Man” (both released in 1980) and “Street Fighter” (released in 1988) sending kids and teens to mall arcades in droves. A favorite food of that same audience? Pizza. So when Nolan Bushnell, the co-founder of Atari, decided to launch a family restaurant filled with animatronic animals and video games that served, you guessed it, pizza, it was a match made in heaven. Chuck E. Cheese —and the trend of "eatertainment"—was born.

The restaurant, featuring a giant rodent mascot and the slogan "Where a kid can be a kid," was a hit. Following the opening of its first San Jose, California, location in 1977, the chain expanded quickly across the country, and rival ShowBiz Pizza bought the brand in 1984.

The eatertainment trend moved beyond pizza when Dave & Buster’s opened its first arcade/sports bar/restaurant in 1982 in Dallas and Medieval Times opened its first U.S. location in Kissimmee, Florida, near Disney World, in 1983, before expanding across North America. The latter's dinner theater-style show, presented in a turreted castle and based on the true story of a noble medieval family, included sword fighting, jousting contests and paper crowns for guests who feasted on hearty fare. 

“A big part of the appeal is that customers become part of the show—sometimes going so far as tossing a chicken bone into the arena to show their support," the Los Angeles Times reported in 1988. "Costumed wenches and serfs serve huge platters of roasted chicken and spare ribs, herb-basted potato and apple tarts. Dinner is served without cutlery, and soup is sipped from bowls."

According to New York Times reporting in 2018, more than 66 million people have taken part in the Medieval Times show since its U.S. debut.

Music Goes Visual

When MTV took to the airwaves in 1981, the world's first music video channel kicked things off with " Video Killed the Radio Star ." And while the song’s concept of that song may not have exactly foretold the future, it certainly changed the way fans viewed musical artists.

The 24-hour music channel, with its moon man logo and a target audience of 12-to 34-year-olds, started as a way to promote new artists by airing videos, music documentaries and concert footage with a rotation of VJs (video jockeys) serving as hosts. Prince, Michael Jackson , Cyndi Lauper, Boy George and others offered conceptual videos that often made headlines and broke barriers. (Jackson's 13-minute short film/music video for “Thriller " was the first of its kind.) Shows including "Yo! MTV Raps," launched in 1988, brought hip-hop culture to the mainstream. And the annual Video Music Awards, started in 1984, not only recognized music videos as a new art form, but garnered huge publicity—think Madonna emerging from a massive wedding cake as she sang "Like a Virgin"—sparking sales of fingerless lace gloves worldwide.

Suddenly, an artist's appearance, visual storytelling ability, dance skills and fashion sense became as important as his or her vocals. Whitney Houston’s colorful “I Wanna Dance With Somebody” party dresses, Rod Stewart’s shaggy “Forever Young” hairdo, Janet Jackson’s “Rhythm Nation” military style and more became instant trends. And, it seems, the channel’s timing was good for making money, too: According to Smithsonian Magazine , cable TV grew to 53 million subscribers by 1989, and soon the world was crying, “I want my MTV!”

The Mall Food Court Has a Heyday

There was a time when people shopped in one place, and when they got hungry, they  went somewhere else to eat. And then came the shopping mall food court, an open-plan collection of food purveyors “expressly designed for shoppers to carbo-load while resting their feet—sustenance to keep them shopping,” according to The Washington Post . To a soundtrack of piped-in music, mall patrons could browse from an array of popular fast-food choices including frothy orange beverages (Orange Julius), mega slices of pizza (Sbarro), Chinese takeout staples (Panda Express) and massive, salt-studded soft pretzels (Auntie Anne’s).

Pioneered in the 1970s by the granddaddy of mall developers, James Rouse, as part of his idea of making the mall a “civic anchor” of the suburbs, the food court mimicked so-called ‘festival marketplace” projects of urban redevelopment like Boston’s Faneuil Hall and Baltimore’s Harborplace. Rouse’s first try at the mall-based food court in 1971 failed, according to Shopping Centers Today  (too small, lacked variety), but he made good on the concept a few years later at the Paramus Park Mall in New Jersey. Rouse believed that the food court, more open than individual restaurant spaces, would provide a place for “community picnics”—without the bugs or inclement weather.

By the 1980s, food courts became a staple of the mall experience—and of suburban culture. It was a place where harried parents could quiet hungry little ones and where teenagers, before cell phones, could congregate, grab an after-school snack and score some people watching—as memorialized in the iconic 1982 teen movie Fast Times at Ridgemont High . 

Toy Crazes Spark Frenzies

Shoppers camped out in line overnight in freezing temps. People ripped boxes from the arms of strangers. A near-riot broke out in Charleston, West Virginia, as 5,000 people showed up to score one of just 120 available dolls.

All that behavior occurred in the name of Cabbage Patch Kids , a toy many described as "homely" that came with an often unusual name, plus a birth certificate, adoption papers and orphan backstory. The dolls, the brainchild of artist Xavier Roberts, hit store shelves in the summer of 1983, and all 2 million produced were sold by fall. As toy company Coleco raced to meet demand, reports quickly emerged of tramplings, fights and other violence by those desperate to purchase the dolls before Christmas.

At a department store in Wilkes-Barre, Pennsylvania a woman suffered a broken leg and four others were injured, The New York Times reported, when 1,000 people rushed the store. "This is my life that's in danger," the manager, clutching a baseball bat, said at the time.

At its peak in 1985, according to Bloomberg , the line made $600 million. But while it earned the most headlines, it wasn't alone in the '80s toy shopping craze trend. Transformer sales reached almost $950 million in the 1980s, including $333 million in 1985 alone, the Associated Press report ed. The Rubik’s Cube sold out during its debut year in 1980. And the animatronic Teddy Ruxpin plush toy that could talk, blink and move its head, sold out during the holiday season of 1985. Even at it's $59-$79 retail price , more than 800,000 dolls were sold that year.

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ENGL 141: Writing about the 80s

Background research.

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Primary Sources from the 1980s

Where to find News & Magazines from the 1980s

• Popular Magazines Database that just has popular magazines. 1980s content is included for 400+ magazines.
• Pop Culture Database of periodicals with pop culture content.
• Journals List This link opens in a new window Use this to find out if we have a specific periodical, what years we carry, and where you can access it.

Where to find Videos from the 1980s

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Pop Culture and Technology of the 1980s

This essay about 1980s culture examines the key elements that defined the decade in the United States, focusing on music, fashion, film, and technology. It highlights how MTV revolutionized the music industry by making music videos a pivotal aspect of an artist’s promotion, helping icons like Michael Jackson and Madonna reach global fame. The essay also explores the era’s distinctive fashion trends, characterized by bold colors and extravagant accessories influenced by these music stars. In film, directors like Steven Spielberg and George Lucas pushed the boundaries of special effects, producing blockbuster hits that captivated diverse audiences. Additionally, the essay discusses the technological advancements of the decade, particularly the rise of personal computers and video gaming, which transformed everyday entertainment and work. Overall, the essay portrays the 1980s as a vibrant period of cultural flamboyance and innovation, whose legacy continues to impact contemporary society.

How it works

The 1980s ushered in a transformative epoch in American cultural milieu, characterized by distinctive trends spanning music, fashion, cinema, technology, and societal paradigms. It was an era where the tenets of Reaganomics wielded substantial influence, MTV reshaped the sonic landscape, and cinematic blockbusters etched indelible imprints on the collective psyche. This exposition delves into the kaleidoscopic tapestry of 1980s cultural dynamics, dissecting the interplay of these facets in shaping the American ethos and imprinting enduring legacies upon the cultural canvas.

In the realm of music, the 1980s bore witness to the ascendancy of the music video and the advent of a revolutionary conduit that broadcasted them into homes nationwide: MTV.

Inaugurated in 1981, MTV catalyzed a paradigm shift in the musical sphere, furnishing artists with a novel platform to disseminate their artistry, thereby elevating luminaries such as Michael Jackson, Madonna, and Prince to global eminence. The paradigm shift orchestrated by the network altered the contours of music marketing, with aesthetic allure assuming parity with auditory allure. The ascendance of pop and rock music attained zeniths, while genres like new wave, synth-pop, and hip-hop attained ascendancy. Concurrently, the epoch bore witness to the emergence of heavy metal behemoths such as Metallica and Guns N’ Roses, who propagated their brand of raucous, defiant rock to vast audiences.

The sartorial landscape of the 1980s was punctuated by audacious chromatic palettes, opulent accouterments, and an ethos of individualism. Informed by the musical luminaries of the era, denizens embraced a cornucopia of voguish inclinations, spanning neon leggings, tattered denims, Members Only jackets, and voluminous blazers. Madonna’s stylistic sway was particularly conspicuous, with her stratified adornments, lace mitts, and tutus ascending to the pantheon of fashion dictums among young femmes, while Michael Jackson’s singular glove and crimson leather jacket attained iconographic status. The sartorial ethos of the 1980s epitomized superfluity and expressive effusion, mirroring the era’s zeitgeist of economic buoyancy and cultural flamboyance.

The cinematic domain burgeoned prodigiously during the 1980s, propelled by the proliferation of cinematic juggernauts and seminal strides in special effects technology. Visionaries such as Steven Spielberg and George Lucas occupied the vanguard, crafting opuses that captivated not solely adolescents but broader demographics. Epics such as “E.T. the Extra-Terrestrial,” “Back to the Future,” and “The Terminator” showcased prodigious technical virtuosity and ensorcelled audiences, setting new benchmarks for celluloid spectacles. Additionally, the epoch witnessed the ascendance of adolescent-oriented cinema, largely attributable to the oeuvre of John Hughes, with classics such as “The Breakfast Club” and “Ferris Bueller’s Day Off” delving into the vicissitudes and jubilations of adolescent existence.

Moreover, the 1980s witnessed seminal strides in digital technology, particularly with the democratization of personal computing. Conglomerates like Apple and IBM democratized access to computers, engendering a paradigm shift in work and leisure paradigms. Simultaneously, the realm of video gaming vaulted into a new epoch with the advent of gaming consoles such as the Nintendo Entertainment System, which metamorphosed into staples of youthful recreation.

In summation, the 1980s epitomized an epoch of resplendent expression and groundbreaking innovation across multifarious cultural domains. Music videos, avant-garde fashion, cinematic blockbusters, and technological breakthroughs constituted the leitmotifs of this ebullient decade. Each of these elements conduced significantly to shaping the cultural tapestry of the 1980s, bequeathing a legacy that endures as a lodestar for contemporary art, fashion, and entertainment. The epoch stands as a compelling testament to the convergent power of cultural constituents in engendering a distinct era that reverberates through the annals of history.

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Industrial Research during the 1980s: Did the Rate of Return Fall?

• Industrial Research during the 1980s: Did the Rate of Return Fall? (Brookings Papers on Economic Activity, 1993, No. 2)

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Bronwyn h. hall bronwyn h. hall university of california, berkeley discussants: adam b. jaffe and abj adam b. jaffe edwin mansfield em edwin mansfield.

Microeconomics 2, 1993

THIS PAPER IS MOTIVATED by two recent empirical findings about the returns to industrial research and development(R&D) at the firm level. First,t he stock market value of R&D spending relative to ordinary capital investment in U.S. manufacturing firms fell precipitously during the 1980s. Second, the contribution of R&D to productivity in these same firms apparently declined from an elasticity of about 0.10-0.15 during the 1960s and 1970S to around 0.02 during the 1980s. Taken together, these findings suggest that something has happened to the marginal private rate of return to industrial R&D during the recent past. The question is, what? This paper explores these prior findings in greater detail in an effort to understand what factors are causing them and to ascertain the pervasiveness of this apparent decline in R&D productivity.

Economic Studies

Brookings Papers on Economic Activity

Lauren Bauer, Bradley Hardy, Olivia Howard

April 17, 2024

Robert Greenstein

Harry J. Holzer

April 16, 2024

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Shell and Exxon's secret 1980s climate change warnings

Newly found documents from the 1980s show that fossil fuel companies privately predicted the global damage that would be caused by their products.

One day in 1961, an American economist named Daniel Ellsberg stumbled across a piece of paper with apocalyptic implications. Ellsberg, who was advising the US government on its secret nuclear war plans, had discovered a document that contained an official estimate of the death toll in a preemptive “first strike” on China and the Soviet Union: 300 million in those countries, and double that globally.

Ellsberg was troubled that such a plan existed; years later, he tried to leak the details of nuclear annihilation to the public. Although his attempt failed, Ellsberg would become famous instead for leaking what came to be known as the Pentagon Papers – the US government’s secret history of its military intervention in Vietnam.

America’s amoral military planning during the Cold War echoes the hubris exhibited by another cast of characters gambling with the fate of humanity. Recently, secret documents have been unearthed detailing what the energy industry knew about the links between their products and global warming. But, unlike the government’s nuclear plans, what the industry detailed was put into action.

In the 1980s, oil companies like Exxon and Shell carried out internal assessments of the carbon dioxide released by fossil fuels, and forecast the planetary consequences of these emissions. In 1982, for example, Exxon predicted that by about 2060, CO 2 levels would reach around 560 parts per million – double the preindustrial level – and that this would push the planet’s average temperatures up by about 2°C over then-current levels (and even more compared to pre-industrial levels).

Later that decade, in 1988, an internal report by Shell projected similar effects but also found that CO 2 could double even earlier, by 2030. Privately, these companies did not dispute the links between their products, global warming, and ecological calamity. On the contrary, their research confirmed the connections.

Shell’s assessment foresaw a one-meter sea-level rise, and noted that warming could also fuel disintegration of the West Antarctic Ice Sheet, resulting in a worldwide rise in sea level of “five to six meters.” That would be enough to inundate entire low-lying countries.

Shell’s analysts also warned of the “disappearance of specific ecosystems or habitat destruction,” predicted an increase in “runoff, destructive floods, and inundation of low-lying farmland,” and said that “new sources of freshwater would be required” to compensate for changes in precipitation. Global changes in air temperature would also “drastically change the way people live and work.” All told, Shell concluded, “the changes may be the greatest in recorded history.”

For its part, Exxon warned of “potentially catastrophic events that must be considered.” Like Shell’s experts, Exxon’s scientists predicted devastating sea-level rise, and warned that the American Midwest and other parts of the world could become desert-like. Looking on the bright side, the company expressed its confidence that “this problem is not as significant to mankind as a nuclear holocaust or world famine.”

The documents make for frightening reading. And the effect is all the more chilling in view of the oil giants’ refusal to warn the public about the damage that their own researchers predicted. Shell’s report, marked “confidential,” was first disclosed by a Dutch news organization earlier this year. Exxon’s study was not intended for external distribution, either; it was leaked in 2015 .

Nor did the companies ever take responsibility for their products. In Shell’s study, the firm argued that the “main burden” of addressing climate change rests not with the energy industry, but with governments and consumers. That argument might have made sense if oil executives, including those from Exxon and Shell, had not later lied about climate change and actively prevented governments from enacting clean-energy policies.

Although the details of global warming were foreign to most people in the 1980s, among the few who had a better idea than most were the companies contributing the most to it. Despite scientific uncertainties, the bottom line was this: oil firms recognized that their products added CO 2 to the atmosphere, understood that this would lead to warming, and calculated the likely consequences. And then they chose to accept those risks on our behalf, at our expense, and without our knowledge.

The catastrophic nuclear war plans that Ellsberg saw in the 1960s were a Sword of Damocles that fortunately never fell. But the oil industry’s secret climate change predictions are becoming reality, and not by accident. Fossil-fuel producers willfully drove us toward the grim future they feared by promoting their products, lying about the effects, and aggressively defending their share of the energy market.

As the world warms, the building blocks of our planet – its ice sheets, forests, and atmospheric and ocean currents – are being altered beyond repair. Who has the right to foresee such damage and then choose to fulfill the prophecy? Although war planners and fossil-fuel companies had the arrogance to decide what level of devastation was appropriate for humanity, only Big Oil had the temerity to follow through. That, of course, is one time too many.

Benjamin Franta, a former research fellow at the Belfer Center for Science and International Affairs at the Harvard Kennedy School of Government, is a doctoral candidate at Stanford University, where his research focuses on the history of climate science and politics.

An earlier version of this piece, entitled “Global Warming’s Paper Trail”, was published on Sept. 12, 2018 by Project Syndicate.

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Alzheimer’s Disease: Past, Present, and Future

Mark w. bondi.

1 Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, California

2 Veterans Affairs San Diego Healthcare System, San Diego, California

Emily C. Edmonds

David p. salmon.

3 Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, California

Although dementia has been described in ancient texts over many centuries (e.g., “Be kind to your father, even if his mind fail him.” – Old Testament: Sirach 3:12), our knowledge of its underlying causes is little more than a century old. Alzheimer published his now famous case study only 110 years ago, and our modern understanding of the disease that bears his name, and its neuropsychological consequences, really only began to accelerate in the 1980s. Since then we have witnessed an explosion of basic and translational research into the causes, characterizations, and possible treatments for Alzheimer’s disease (AD) and other dementias. We review this lineage of work beginning with Alzheimer’s own writings and drawings, then jump to the modern era beginning in the 1970s and early 1980s and provide a sampling of neuropsychological and other contextual work from each ensuing decade. During the 1980s our field began its foundational studies of profiling the neuropsychological deficits associated with AD and its differentiation from other dementias (e.g., cortical vs . subcortical dementias). The 1990s continued these efforts and began to identify the specific cognitive mechanisms affected by various neuropathologic substrates. The 2000s ushered in a focus on the study of prodromal stages of neurodegenerative disease before the full-blown dementia syndrome (i.e., mild cognitive impairment). The current decade has seen the rise of imaging and other biomarkers to characterize preclinical disease before the development of significant cognitive decline. Finally, we suggest future directions and predictions for dementia-related research and potential therapeutic interventions.

INTRODUCTION

One of the great challenges faced by neuropsychologists over the past 50 years is to understand the cognitive and behavioral manifestations of dementia and their relationship to underlying brain pathology. This challenge has grown substantially over the years with the aging of the population and the age-related nature of many dementia-producing neurodegenerative diseases. Although the concept of dementia has existed for thousands of years ( Mahandra, 1984 ), it is only early in the past century that the essential clinical syndrome and associated neurodegenerative changes were first discovered. In 1907, Aloysius “Alöis” Alzheimer carefully described the symptoms of a 51-year-old woman, Auguste Deter, who was under his care at the state asylum in Frankfurt Germany ( Alzheimer, 1907 ; for an English translation, see Stelzmann et al., 1995 ) ( Figure 1 ). Alzheimer’s description of her symptoms is almost certainly the first neuropsychological characterization of the disease:

“ Her memory is seriously impaired. If objects are shown to her, she names them correctly, but almost immediately afterwards she has forgotten everything. When reading a test, she skips from line to line or reads by spelling the words individually, or by making them meaningless through her pronunciation. In writing she repeats separate syllables many times, omits others and quickly breaks down completely. In speaking, she uses gap-fills and a few paraphrased expressions (“milk-pourer” instead of cup); sometimes it is obvious she cannot go on. Plainly, she does not understand certain questions. She does not remember the use of some objects .”

Photographs of Alois Alzheimer (left) and his patient Auguste Deter (right).

When Auguste Deter died, Alzheimer used the then-new silver staining histological technique to examine her brain microscopically. When he did so, he observed the neuritic plaques, neurofibrillary tangles, and amyloid angiopathy that were to become the hallmarks of the disease that now bears his name (as shown in Figure 2 from sketches of the histologic preparations in his 1911 paper). Alzheimer himself did not claim to have discovered “Alzheimer’s disease,” although his mentor Emil Kraepelin at the Munich Medical School rightly credited him with doing so by coining the term in his own Handbook of Psychiatry ( Kraepelin, 1910 ). By 1911, the medical community was using Alzheimer’s depictions of the disease to diagnose patients both in Europe and the United States (Mauer & Mauer, 2003).

Sketches of Auguste Deter’s histopathologic preparations of early and late stage neurofibrillary tangle pathology as drawn by Alzheimer from his 1911 paper entitled “Über eigenartige Krankheitsfälle des späteren Alters.”

It was also during this time that Eugen Blueler in his study of schizophrenia coined the term “organic psychosyndrome” to refer to decrements in memory, judgment, perceptual discrimination and attention, emotional lability, and defective impulse control associated with chronic diffuse cortical damage. This classification was essentially adopted by the American Psychiatric Association (APA) to define dementia in the first two editions of their Diagnostic and Statistical Manual of Mental Disorders (DSM). Specifically, DSM-II defined “organic brain syndrome” as a “basic mental condition characteristically resulting from diffuse impairment of brain tissue function from whatever cause,” and which is manifested behaviorally as impairment in orientation, memory, intellectual functions, judgment, and affect ( APA, 1968 ).

Armed with these uniform criteria and newly developed standardized bedside cognitive screening tests ( Blessed, Tomlinson, & Roth, 1968 ; Folstein, Folstein, & McHugh, 1975 ), a handful of investigators began scientific studies of dementia, particularly focusing on dementia associated with Alzheimer’s disease (AD). Although dementia is associated with more than 70 different causes of brain dysfunction, AD is the most common cause accounting for roughly half of all cases (for review, see Cummings & Benson, 1992 ). One of the most important studies during this period showed that the degree of AD pathology in the brain was significantly correlated with performance on standardized cognitive tests shortly before death ( Blessed, Tomlinson, & Roth, 1968 ). This was the first study to strongly link the clinical features of AD with the pathologic brain changes that Alzheimer had described ( Figure 3 ).

Mean plaque count plotted against the summary cognitive test score constructed by Blessed, Tomlinson, & Roth (1968) . The “Blessed” test score was computed from “a number of simple psychological tests of orientation, remote memory, recent memory, and concentration,” resulting in a total score ranging from 0 (complete failure) to 37 (perfect score). The scatterplot resulted in a highly significant correlation coefficient of −0.59 ( p <.001) (from Blessed, Tomlinson, & Roth, 1968 ).

Neuropsychological studies of dementia and AD during this period were rare and largely limited to presenile dementia with onset before the age of 65. A notable exception was a series of studies by Edgar Miller who showed that the main behavioral feature of presenile AD is a memory disorder in which recently acquired information fails to reach long-term memory storage due to both an abnormally rapid loss of material from short-term storage (perhaps due to encoding inefficiency) and difficulty in transferring information between short-term and long-term storage systems ( Miller, 1971 , 1973 ). He also suggested that inefficient retrieval of information from long-term storage may contribute to the memory deficit in presenile AD ( Miller, 1975 , 1978 ). These early studies set the stage for countless subsequent studies that examined the nature of memory dysfunction in AD in the decades to follow (for reviews, see Salmon & Bondi, 2009 ; Smith & Bondi, 2013 ).

A major sea-change in the study of dementia occurred in 1976 when Robert Katzman summarized data showing that senile and presenile AD were histopathologically identical and suggested that, based on epidemiological data, AD was the fourth leading cause of death in the elderly ( Katzman, 1976 ). Suddenly, AD dementia went from a relatively rare condition to a major public health issue. This led to greater attention to the disease by the public and at the National Institutes of Health, which established the National Alzheimer’s Disease Research Center program to study the cause, neuropathology, and clinical characteristics of AD. At this time, the diagnostic criteria for dementia were refined in the DSM-III ( American Psychiatric Association, 1980 ) and International Statistical Classification of Diseases and Related Health Problems, 10th Revision ( World Health Organization, 1992 ), and specific research diagnostic criteria for AD were established ( McKhann et al., 1984 ).

Also notable at this time was a growing realization that various dementing disorders are associated with patterns of relatively preserved and impaired cognitive abilities that vary depending upon the etiology and neuropathology of the underlying disease. Martin Albert and his colleagues ( Albert, Feldman, & Willis, 1974 ) referred to the pattern of cognitive dysfunction observed in patients with progressive supranuclear palsy as a “subcortical dementia” characterized by forgetfulness, slowness of thought processes, altered personality with apathy or depression, and impaired ability to manipulate acquired knowledge. Similar cognitive changes were noted in patients with Huntington’s disease ( McHugh & Folstein, 1975 ). This pattern of impairment was contrasted with the cortical dementia (e.g., frank amnesia, aphasia, and agnosia) observed in AD. Subsequent studies further delineated qualitative differences in the cognitive deficits associated with so-called “cortical” and “subcortical” dementing disorders ( Huber, Shuttleworth, Paulson, Bellchambers, & Clapp, 1986 ; Salmon, Kwo-on-Yuen, Heindel, Butters, & Thal, 1989 ), and several investigators suggested that these two forms of dementia should be recognized as distinct clinical syndromes (for reviews, see Cummings & Benson, 1992 ; Cummings, 1990 ).

THE 1990s: NEUROPSYCHOLOGICAL CHARACTERIZATION OF ALZHEIMER’S DISEASE AND RELATED DISORDERS

The new criteria for dementia and AD adopted in the 1980s improved the reliability of the clinical diagnosis and allowed group studies of mildly demented patients to be carried out with a reasonable degree of accuracy. Many of these studies applied the theories and methods of cognitive psychology to study the cognitive consequences of AD. By using this approach, these studies characterized the component cognitive processes underlying the neuropsychological deficits observed in AD, and showed that cognitive changes attributable to AD and other dementing disorders could have important implications for existing theories of brain–behavior relationships underlying normal cognition.

Several studies at this time showed that episodic memory impairment (i.e., amnesia) is usually the earliest and most salient aspect of the AD dementia syndrome. These findings were consistent with neuropathologic studies that showed extensive AD pathology occurs earliest in medial temporal lobe (MTL) structures (e.g., hippocampus, entorhinal cortex) important for episodic memory ( Hyman et al., 1984 ). The memory deficit was shown to reflect an inability to effectively encode and store new information since patients with very early AD were particularly impaired on measures of delayed recall (i.e., have abnormally rapid forgetting), exhibited an abnormal serial position effect with attenuation of the primacy effect (i.e., recall of words from the beginning of a list), and remained impaired even if retrieval demands were reduced by the use of recognition testing (e.g., Delis et al., 1991 ).

Semantic encoding was found to be less effective in improving the episodic memory performance of patients with AD than normal elderly individuals ( Buschke, Sliwinski, Kuslansky, & Lipton, 1997 ). In addition, patients with AD more often produced intrusion errors (i.e., previously learned information is produced during the attempt to recall new material) on both verbal and non-verbal memory tests, presumably due to increased sensitivity to interference and/or decreased inhibitory processes ( Butters, Granholm, Salmon, Grant, & Wolfe, 1987 ; Jacobs, Salmon, Tröster, & Butters, 1990 ). This pattern of memory deficits was shown to differ from the pattern exhibited by patients with subcortical dementia who had difficulty learning new information, but retained what was learned well and showed improved performance with retrieval aids (e.g., cueing or recognition formats) ( Cummings, 1990 ). These findings provided evidence of differential roles of MTL and fronto-striatal brain structures in memory performance.

Studies also showed that, as the neuropathology of AD spreads beyond MTL structures to adjacent temporal, parietal, and frontal association cortices, several higher order cognitive abilities became affected. A deficit in language abilities (i.e., aphasia) was observed relatively early in the course of AD, with deficits in confrontation naming, verbal fluency (particularly from semantic categories), semantic categorization, and a reduced ability to recall over-learned facts (e.g., the number of days in a year) ( Hodges & Patterson, 1995 ; Nebes, 1989 ). Patients were highly consistent in the individual items they missed across different semantic memory tests that used unique modes of access and output (e.g., fluency versus confrontation naming; Chertkow & Bub, 1990 ; Hodges, Salmon, & Butters, 1992 ), or within the same test across serial evaluations ( Norton, Bondi, Salmon, & Goodglass, 1997 ).

These findings demonstrated that AD results in a true loss of semantic knowledge (i.e., general knowledge and the meanings of words) rather than only an impaired ability to retrieve information from intact semantic memory stores (also see Salmon, Heindel, & Lange, 1999 ). A similar loss of knowledge was thought to contribute to the severe deficit patients with AD exhibited in the ability to remember past events that were successfully remembered before the onset of the disease (i.e., retrograde amnesia) ( Squire, 1987 ). Patients with subcortical dementia or fronto-temporal dementia, in contrast, retained semantic knowledge well, but had difficulty in systematic retrieval from semantic memory stores ( Rosser & Hodges, 1994 ; Rascovsky, Salmon, Hansen, Thal, & Galasko, 2007 ).

Deficits in “executive” functions responsible for concurrent mental manipulation of information, concept formation, problem solving, and cue-directed behavior were found to develop in the course of AD ( Bondi, Monsch, Butters, Salmon, & Paulsen, 1993 ; Lefleche & Albert, 1995 ; Perry & Hodges, 1999 ). Attention deficits were also found to occur and were usually evident on dual-processing tasks, tasks that require the disengagement and shifting of attention, and working memory tasks that depend upon the control of attentional resources (for reviews, see Parasuraman & Haxby, 1993 ; Perry & Hodges, 1999 ). Deficits in working memory were relatively mild and primarily characterized by disruption of the “central executive” with relative sparing of immediate memory ( Baddeley, Bressi, Della Sala, Logie, Spinnler, 1991 ; Collette, Van der Linden, Bechet, Salmon, 1999 ). Executive dysfunction and deficits in attention played a less prominent role in the AD dementia syndrome than in the subcortical dementia syndrome associated with fronto-striatal dysfunction.

Several studies showed that visuospatial deficits occurred in patients with AD (for review, see Cronin-Golomb & Amick, 2001 ), but these deficits were usually less salient than other cognitive deficits in the early stages of the disease ( Storandt Botwinick, Danziger, Berg, Hughes, 1984 ). Visuospatial tasks that were sensitive to early AD often involved not only visuoperceptual and constructional aspects of performance, but also required conceptual knowledge (e.g., Clock Drawing; Rouleau, Salmon,, Butters, Kennedy, & McGuire, 1992 ) or planning ability (e.g., Block Design).

The advances made in characterizing the neuropsychological deficits associated with AD had a major impact on the ability to accurately diagnose the disease in its early stages. This clinical utility was demonstrated in a study that compared the ability of several sensitive measures of learning and memory, executive abilities, language, and visuospatial abilities to differentiate between mild AD and matched normal control subjects ( Salmon et al., 2002 ). Results showed excellent sensitivity and specificity for learning and delayed recall measures from the California Verbal Learning Test (CVLT) (sensitivity: 95–98%, specificity: 88–89%), category fluency (sensitivity: 96%, specificity: 88%), and Trail-Making Part B (sensitivity: 85%, specificity: 83%). The best-fitting combination of category fluency and delayed recall accurately classified 96% of the patients with AD and 93% of the control subjects (see Figure 4 ). This study also illustrated that the pattern of cognitive deficits typically associated with AD is characterized by prominent deficits in episodic and semantic memory, with additional, although somewhat less prominent, deficits in executive functions, visuospatial abilities, and attention.

Receiver operating characteristic curves demonstrating excellent sensitivity and specificity for the accurate diagnosis of early AD achieved with neuropsychological tests of memory (California Verbal Learning Test), language (category fluency: animals, fruits, and vegetables) and executive functions (Trail-Making Test: Part B) (adapted from Salmon et al., 2002 ).

There are, however, somewhat rare instances, particularly in younger patients (e.g., less than 65 years old), where AD initially presents with dementia dominated by higher-order visual dysfunction, executive dysfunction or deficits in language. Posterior cortical atrophy (PCA) occurs when there is disproportionate atrophy and deposition of neurofibrillary tangles and neuritic plaques in the occipital cortex and posterior parietal cortex relative to other cortical association areas ( Hof, Vogt, Bouras, & Morrison, 1997 ; Renner et al., 2004 ). Patients with PCA usually have prominent visual agnosia (sometimes including prosopagnosia) and constructional apraxia, and exhibit many or all of the features of Balint’s syndrome, including optic ataxia, gaze apraxia, and simultanagnosia (i.e., can detect visual details of an object but cannot organize them into a meaningful whole) ( Caine, 2004 ; Mendez et al., 2002 ; Renner et al., 2004 ). PCA is associated with posterior cortical hypometabolism with particular involvement of the dorsal visual stream ( Nestor, Caine, Fryer, Clarke, & Hodges, 2003 ), and with a posterior distribution of amyloid deposition revealed by positron emission tomography (PET) imaging using Pittsburgh compound-B ([ 11 C]-PIB) ( Tenovuo, Kemppainen, Aalto, Nagren, & Rinne, 2008 ).

A frontal variant of AD was identified in a subgroup of patients with autopsy-confirmed AD who initially presented with disproportionately severe deficits on neuropsychological tests of frontal lobe functioning ( Johnson, Head, Kim, Starr, & Cotman, 1999 ). These patients had a significantly higher burden of neurofibrillary tangles, but not neuritic plaques, in the frontal cortex than a matched group of patients with a typical clinical presentation of AD. A subset of patients with primary progressive aphasia (PPA) was found to have AD pathology. These patients usually presented with logopenic PPA (PPA-L), which is characterized by hesitant, grammatically correct speech and spared language comprehension ( Gorno-Tempini et al., 2004 ). PPA-L is most often associated with AD pathology disproportionately distributed in language-related cortical areas ( Mesulam et al., 2008 ).

The existence of these AD “variants” has complicated the clinical and neuropsychological differentiation of AD from other neurodegenerative diseases that may have a different underlying focal pathology such as frontotemporal lobe dysfunction (FTLD), dementia with Lewy bodies (DLB), or PPA. However, considerable work has been done to identify how the neuropsychological presentations of these disorders differs from that of typical AD, and this information has been incorporated into the most recent clinical diagnostic criteria for behavioral variant FTLD ( Rascovsky et al., 2011 ), DLB ( McKeith et al., 2017 ), and PPA ( Gorno-Tempini et al., 2011 ).

During the 1990s and early 2000s, important advances were also made in identifying genetic risks for AD. Mutations on three separate genes were identified in large families that displayed an autosomal dominant inheritance pattern of an early-onset form of AD (i.e., onset generally before the age of 60): the amyloid precursor protein gene on chromosome 21, the presenilin 1 gene on chromosome 14, and the presenilin 2 gene on chromosome 1 (for review, see Bird, 1999 ). These forms of familial AD are rare and account for only approximately 1 to 2% of all cases of the disease. A far more common genetic risk factor for sporadic, late-onset AD was identified as the type ε4 allele of the gene for apolipoprotein E (APOE), a low density lipoprotein cholesterol carrier ( Strittmatter et al., 1993 ). Located on chromosome 19, the APOE ε4 allele was found to be present in 50 to 60% of patients with AD (compared to 20 to 25% of healthy older adults), regardless of whether or not they have a family history of dementia ( Strittmatter, et al., 1993 ). Unlike the genes associated with early-onset familial AD, the APOE ε4 allele is not deterministic, but confers an approximately three-fold risk of developing AD if one copy of the ε4 allele is present, and an eight-fold risk if two copies are present ( Katzman & Kawas, 1994 ).

The identification of the APOE ε4 risk led to a new approach to examining potential decrements in learning and memory during a “preclinical” phase of AD. The performance of non-demented older adults who have an increased risk for developing the disease due to an APOE ε4 genotype could be compared to that of individuals who do not have this risk factor with the presumption that more individuals with the ε4 genotype are in a preclinical stage of the disease. In one such study, Bondi, Salmon, Galasko, Thomas, and Thal (1999) compared the neuropsychological test performances of non-demented elderly individuals with or without at least one APOE ε4 allele. Although the groups did not differ significantly in age, education, or global cognitive status, the ε4+ subjects performed significantly worse than the ε4− subjects on measures of delayed recall, but not on tests of other cognitive abilities.

Cox proportional hazards analysis showed that APOE ε4 status and measures of delayed recall were significant independent predictors of subsequent progression to AD, suggesting that poor recall is an early sensitive neuropsychological marker of AD and not a cognitive phenotype of the ε4 genotype (also see Bondi et al., 1995 ; Petersen et al., 1995 ; Reed et al., 1994 ). Although ApoE remains the most potent susceptibility gene, the advent of genome wide association studies have identified 25 loci known to associate with late-onset sporadic AD, and the advent of polygenic risk scores are now available and will further refine our understanding of genetic contributions to AD progression (for review, see Sims & Williams, 2016 ).

THE 2000s: “MILD COGNITIVE IMPAIRMENT”

Although in the 1990s a few investigators had begun to systematically study individuals at risk for dementia to determine whether cognitive declines could be detected before diagnosis ( Bondi et al., 1994 , 1999 ; La Rue, Matsuyama, McPherson, Sherman, & Jarvik, 1992 ; Small, Fratiglioni, Viitanen, Winblad, & Bäckman, 2000 ; Snowdon et al., 1996 ), following the turn of this century, the focus of the field heavily shifted to the study of prodromal stages of AD that precede the full-blown dementia syndrome. Characterization of such early phases was largely crystallized by Ron Petersen, Glenn Smith, and colleagues from the Mayo Clinic who introduced of the concept of “mild cognitive impairment” (MCI) ( Petersen et al., 1999 ).

MCI was defined as a condition in which individuals experience memory loss to a greater extent than one would expect for age, yet do not meet criteria for dementia. The specific clinical criteria for MCI they originally put forth were: (1) subjective memory complaint, (2) objective memory impairment for age, (3) relatively preserved general cognition, (4) essentially intact activities of daily living, and (5) not demented ( Petersen et al., 1999 ). This classification scheme was subsequently broadened to include “amnestic MCI” or “non-amnestic MCI” subtypes, and “single domain” or “multiple domain” conditions to indicate the number of cognitive domains affected ( Petersen, 2004 ; Winblad et al., 2004 ). It was proposed that these MCI subtypes correspond to various etiologies, with “amnestic MCI” being most indicative of AD and “non-amnestic MCI” suggesting other neurodegenerative conditions such as FTLD or DLB ( Petersen & Morris, 2005 ; see also Smith & Bondi, 2013 , for review).

With the advent of these new criteria, the study of MCI became widespread during the 2000s. To illustrate this increasing attention and productivity, Petersen and colleagues (2009) noted that in 1999 fewer than 50 papers were published in the medical literature on the topic of MCI, whereas by 2007, this number approached 900 peer-reviewed studies in that year alone (see Figure 5 ). He rightly concluded that the increased awareness and study of MCI had been extremely valuable for the field by enhancing our understanding of the early neuropsychological manifestations of AD and improving the ability to identify those at risk for progression to dementia.

A representative number of publications with the search term “mild cognitive impairment” in the title or abstract from 1990 through part of 2008. Note the exponential rate of increase in the numbers of publications during the 2000s (from Petersen et al., 2009 ).

Detection and characterization of prodromal AD continued to be a vibrant area of research moving into the 2010s. In 2011, the National Institute on Aging and Alzheimer’s Association (NIA-AA) published updated diagnostic guidelines for MCI ( Albert et al., 2011 ) and introduced research criteria for “preclinical” AD ( Sperling et al., 2011 ). The new guidelines for MCI largely retained the criteria developed by Petersen and colleagues, but expanded the subjective cognitive complaint criterion to allow the complaint to come from either the patient, an informant or a skilled clinician, and incorporated the use of biomarkers into the diagnosis (discussed below). Research began on the potential of subjective cognitive complaints alone to accurately signal the development of underlying AD pathology (for review, see Jessen et al., 2014 ). Criteria for “preclinical” AD were developed to identify at-risk individuals at a stage of disease when they were still considered “asymptomatic” (i.e., had no significant cognitive impairment in the presence of one or more positive biomarkers for AD).

Although the criteria for MCI have been widely adopted, recent research has demonstrated limitations in the way the criteria were operationalized for clinical trials (e.g., Petersen et al., 2005 ) and large-scale natural history studies (e.g., the Alzheimer’s Disease Neuroimaging Initiative or ADNI; Weiner et al., 2013 ). These studies operationalized MCI as subjective complaints about memory, normal performance on simple cognitive screens, marginal memory ratings on scales based on clinical judgment, and impaired performance on a single memory test. Unfortunately, this method appears to be highly susceptible to false positive diagnostic errors ( Bondi et al., 2014 ; Clark et al., 2013 ; Edmonds, Delano-Wood, Clark, et al., 2015 ).

This susceptibility was demonstrated by Edmonds, Delano-Wood, Clark, et al. (2015) who applied cluster-analytic statistical techniques to the neuropsychological test scores of participants in the ADNI cohort who had been classified as MCI using the conventional criteria. Despite their MCI diagnosis , approximately one-third of these participants performed within normal limits on this more extensive cognitive testing and showed a low rate of progression to dementia. Given these limitations in the conventional diagnostic criteria, Jak, Bondi, and colleagues ( Jak et al., 2009 , Bondi et al., 2014 ) developed an actuarial neuropsychological diagnostic method to identify individuals with MCI. Rather than using a single memory test, a diagnosis of MCI is established on the basis of scores achieved on multiple objective neuropsychological tests that assess a range of cognitive domains without reference to subjective complaints or clinical judgment. This actuarial method was shown to produce greater diagnostic stability than the conventional method (i.e., individuals classified as MCI did not revert to “normal” cognition after 1 year; Jak et al., 2009 ), and revealed stronger relationships between cognition, biomarkers, and rates of progression to dementia in patients classified as MCI in this way ( Bondi et al., 2014 ).

THE 2010s: THE ERA OF BIOMARKERS

Over the past 20 years great progress was made in identifying in vivo biological markers of AD. Several investigators refined the ability to detect and measure cerebrospinal fluid levels of Aβ (the main constituent of the plaque) and tau protein (a constituent of the neurofibrillary tangle) that were indicative of AD pathology in the brain. Klunk and colleagues (see Mathis et al., 2003 ) developed Pittsburgh compound-B ([ 11 C]-PIB), an agent that binds to Aβ, for use with PET imaging to reveal deposition of amyloid in the brain. Tau-binding agents that can be used with PET imaging have also been recently developed (for review, see Brosch, Farlow, Risacher, & Apostolova, 2017 ).

Neuroimaging measures of hippocampal, cortical, and general brain atrophy were developed and applied to detect early neurodegenerative changes associated with AD (for review, see Frisoni, Fox, Jack, Scheltens, & Thompson, 2010 ). Other advanced structural and functional neuroimaging methodologies, including resting-state functional MRI and diffusion tensor imaging, have been used to detect pathological changes associated with AD and to create algorithms for classifying AD and MCI (for review, see Rathore, Habes, Iftikhar, Shacklett, & Davatzikos, 2017 ). All of these biomarkers have greatly increased the accuracy with which AD pathology in the brain can be detected before the onset of cognitive symptoms, and improved the ability to differentiate AD from other pathologies that lead to dementia.

In the current decade, several large-scale longitudinal studies have examined the relationship between various AD biomarkers and the development of cognitive decline and dementia (e.g., ADNI, Australian Imaging, Biomarkers, and Lifestyle study). Based on results from these studies, Jack and colleagues (2010) proposed a hypothetical model of dynamic biomarker changes in the development of AD. Their model, consistent with the amyloid cascade hypothesis , proposed that amyloid deposition related to abnormal processing of the amyloid precursor protein (i.e., amyloidosis) drives the formation of abnormal tau aggregates. This in turn leads to tangle-mediated neuronal injury and neurodegeneration, which then produces cognitive and functional impairment (see Jack et al., 2010 , 2013 , for discussion).

Many biomarker studies align with this temporal sequence of pathophysiologic changes, particularly in early-onset autosomal dominant mutation carriers (e.g., Bateman et al., 2012 ). The model has been very influential in the development of treatment strategies for AD because it posits that, if the preclinical build-up of amyloid can be blocked or built-up, amyloid can be cleared and the cascade of events that leads to cognitive decline and dementia can be prevented (for review, see Musiek & Holtzman, 2015 ). The hypothesis also provided the framework for revised diagnostic criteria for AD ( McKhann et al., 2011 ), MCI ( Albert et al., 2011 ), and preclinical AD ( Sperling et al., 2011 ).

Despite its wide influence, there is increasing evidence that calls the amyloid cascade hypothesis into question, especially with regard to its invariant temporal sequence of pathological events ( Drachman, 2014 ). Several studies, for example, have shown that neurodegeneration (measured by tau biomarkers or neuroimaging measures of atrophy) can occur before amyloidosis in individuals with prodromal AD ( Braak, Zetterberg, Del Tredici, & Blennow, 2013 ; Knopman et al., 2013 ; Ryan et al., 2013 ; Sheline et al., 2010 ; Wirth et al., 2013 ). Neurodegeneration in the face of normal amyloid levels was evident in 23% of the original sample of Jack et al. (2010) (and in an even higher percentage in Edmonds, Delano-Wood, Galasko, et al., 2015 ). Axonal injury ( Ryan et al., 2013 ) and tau lesions in late-myelinating regions ( Braak et al., 2011 ) have been shown to predate amyloid deposition in prodromal AD.

In addition, a growing number of studies have shown that cognitive measures can be as sensitive as physical biomarkers in predicting progression to dementia ( Gomar et al., 2014 ; Heister et al., 2011 ; Jedynak et al., 2012 ; Landau et al., 2010 ; Richard, Schmand, Eikelenboom, Van Gool; Alzheimer’s Disease Neuroimaging Initiative, 2013 ). Taken together, these findings strongly suggest that the neurodegeneration of AD may not depend upon prior amyloidosis ( Knopman et al., 2013 , but cf. Jack, Knopman, et al., 2016 ).

Our prior work ( Edmonds, Delano-Wood, Galasko, et al., 2015 ) in this area confirms that biomarker development in most individuals with preclinical/prodromal AD does not follow the temporal order proposed by the amyloid cascade hypothesis. We have shown that cognitively normal individuals who later progressed to MCI or AD, and had only one abnormal biomarker at baseline, were most likely to have neurodegeneration (i.e., P-tau positivity) as that abnormal biomarker rather than either amyloidosis alone or subtle cognitive deficit alone. In fact, neurodegeneration in isolation was 2.5 times more common than amyloidosis alone.

Jack, Bennett, and colleagues (2016) have recently acknowledged these and similar findings and proposed a more descriptive classification scheme for AD biomarkers that is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis. This new model, known as the A/T/N system (“A” refers to Aβ, “T” to tau, and “N” to neurodegeneration), makes no assumptions about temporal ordering of biomarkers or their putative causal relationships. This “agnosticism” concurs with the notion of a simple tallying of biomarker risks as previously suggested by Edmonds, Delano-Wood, Galasko, et al. (2015) .

Such a dramatic shift away from the strictures of the amyloid cascade model toward a more equipotential conceptualization of AD biomarker risks espoused by our tally system and by the A/T/N classification system fits well with a continuum hypothesis proposed by Braak and colleagues. An original Braak staging theory proposed that progression of neurofibrillary tangle pathology proceeds along well-defined predilection sites beginning in the MTL and then expands to adjacent association cortices and beyond ( Braak & Braak, 1991 ). Amyloid plaque pathology, in contrast, accumulates more diffusely across neocortex.

This theory was recently updated to suggest that the pathogenic process actually starts with the formation of pretangle material in the lower brainstem with the first visible pathologic changes occurring in the locus coeruleus ( Braak et al., 2011 ). Tangle pathology then spreads (possibly through cell-to-cell propagation; Iba et al., 2015 ) to MTL through specific projections from the locus coeruleus. It is postulated that this begins well before amyloidosis. Braak and Del Tredici (2015) proposed that the initial tau pathology in locus coeruleus and its axonal projections may not result in outright neuronal death, but may restrict neuronal function. Thus, a central role of neuropsychology in the coming decades may be to provide sophisticated measurement of functionality of affected neural systems in preclinical/prodromal AD.

Critics of the continuum theory argue that tau aggregation confined to brainstem structures and MTL, in the context of little to no amyloid deposition, should be considered an independent pathological process that is not integral to the developmental continuum of sporadic AD. They have termed this condition primary age-related tauopathy (PART; Crary et al., 2014 ). In this view, the pathological diagnosis of AD requires the presence of amyloid pathology. Braak and Del Tredici (2014) counter this argument by suggesting that amyloid plaques may develop after neurofibrillary tangle pathology develops in sites associated with AD (e.g., MTL); therefore, the “absence of Aβ deposits is not an adequate rationale for excluding tau-only cases from the developmental spectrum of the AD-related process.” They further argue that requiring a minimum threshold level of amyloid deposition for a neuropathologic diagnosis of AD (as in the PART criteria) may be justified only when applied in cases with clinically evident dementia, but not when applied to non-demented individuals.

As we move toward the end of the current decade, it is clear that the dogma that “amyloidosis is AD” is giving way to a broader conceptualization of the disease. This is evident in the adoption of biomarker staging systems that are agnostic to the temporal order of their occurrence (e.g., a tally system or the A/T/N system), and with the acceptance of new evidence that brainstem tauopathy and its propagation to the MTL may occur before amyloidosis associated with late-onset sporadic AD. This new understanding of AD may drive fundamental shifts in biomarker strategies, drug discovery, and therapeutics.

Neuropsychology has played a critical role in characterizing the cognitive changes associated with AD and related dementing disorders. This has improved the ability to accurately diagnose AD and differentiate it from other dementing disorders, to identify subtle cognitive changes that occur in the preclinical/prodromal phase of disease, and to track progression of the disease over the aging-MCI-AD continuum. Recent advances in AD biomarker development will alter this role. Increasingly, diagnosticians and investigators will be asked to use an array of available biomarkers to identify the neuropathologic determinants underlying cognitive changes within a given individual, and to detect neuropathology in its earliest stages before the onset of significant cognitive change.

That is not to say, however, that neuropsychology will cease to play an important role in dementia assessment and research. Regardless of the underlying pathology, it remains a critical function to identify the onset and nature of the earliest cognitive deficits that might impact someone’s life, to be able to predict the course of cognitive decline, and to measure the cognitive outcome of future treatments. These functions will likely be enhanced by integrating biomarker information into assessments. The use of such a “precision medicine” approach might bring increased specificity to the study of dementia in the future.

It has also become clear that, as age increases, there is increasing heterogeneity in the neuropathology underlying what is clinically diagnosed as “AD dementia.” Nelson and colleagues (2011) showed that the prevalence of AD pathology increases with age but reaches a plateau at approximately age 90; however, the prevalence of dementia and other pathologies, such as cerebrovascular disease or hippocampal sclerosis (arteriolosclerosis more generally), continue to increase with age (see Figure 6 ). This observation suggests that, in some cases, “AD dementia” appears only following the addition of other pathologies to a sub-threshold level of AD pathology. Such pathological heterogeneity leads to neuropsychological heterogeneity, making dementia characterization and differential diagnosis more difficult.

Nelson et al.’s (2011) contrasting depictions of the epidemiology of dementia. Panel (a) is the schematic representation of the prevailing view of Alzheimer neuropathology by age, whereas panel (b) depicts distinct brain diseases other than AD that may contribute to cognitive impairment in late life (adapted from Nelson et al., 2011 ).

In the future, a precision medicine approach will allow multiple biomarkers to target distinct pathologies to show which pathologies are present, a genetic analysis will allow polygenic risk for various disorders to be assessed, and neuropsychological assessment will identify distinct patterns of deficits that reflect the differential impact of distinct pathologies on the dementia syndrome. Movement toward this goal is illustrated in a recent study which showed that individuals diagnosed as amnestic MCI in the ADNI cohort had great heterogeneity in the pattern of cognitive deficits they exhibited and that their deficits coincided well with specific regions of cortical thinning on neuroimaging (see Figure 7 ; Edmonds et al., 2016 ). These results demonstrate the potential utility of a combination of neuropsychological assessment and neuroimaging biomarkers to help explain a heterogeneous presentation of prodromal AD.

Regional cortical thickness maps of the left and right lateral and medial pial surfaces for each neuropsychological MCI subtype relative to normal control (NC) participants ( Edmonds et al., 2016 ). The scale indicates group differences in cortical thickness at p < .0001. The cyan/blue shades represent areas where the MCI subgroup has significantly thinner cortex than the NC group. Cluster-derived normal (CDN) = those participants who performed normally across the neuropsychological tests but whom ADNI diagnosed as MCI. Their maps show no areas of cortical thinning relative to the NC group, suggesting they are false-positive diagnostic errors. Our prior work showing the CDN subgroup to have normal CSF AD biomarkers and low progression rates adds to the inference that they received false-positive MCI diagnoses ( Bondi et al., 2014 ).

Neuropathological heterogeneity in AD could also have important implications for future therapeutic approaches to the disease. Given the shift away from the amyloid cascade model toward a more equipotential conceptualization of AD, it is not surprising that the recent singular focus on anti-amyloid treatments has led to disappointing results ( Cummings, Morstorf, & Zhong, 2014 ). In an equipotential model of AD, other aspects of AD related pathology may already exist, continue to develop, and adversely affect cognition even if amyloid pathology is removed. If patients in anti-amyloid trials are positive for significant levels of amyloid, the anti-amyloid agent engages and clears amyloid, yet there is no clinical or cognitive benefit, it is reasonable to presume that pathology other than amyloid needs to be targeted.

Since tau pathology is more firmly associated with clinical and cognitive decline than is amyloid pathology, and may accumulate in susceptible regions earlier than that of amyloid, tau-altering pharmacologic interventions would seem worthwhile. Specific therapeutics may also be needed for other underlying pathologies (e.g., arteriolosclerosis, blood–brain barrier dysfunction, α-synuclein) that could be interacting with abnormal amyloid and tau in older individuals with sporadic “AD dementia.” Such agents could be used in a “precision medicine” context, where aberrant biomarkers coupled with a specific pattern of neuropsychological deficits could specify a particular treatment regimen within a prevention framework. Such a framework would also be accommodative of the specter of multiple biomarker abnormalities occurring concurrently.

Over the past century since Alzheimer’s original publication, we have witnessed an explosion of work in the neuropsychology of dementia, and we have much work yet to complete. To borrow from another prominent psychologist who spoke of his perspective to better understand schizophrenia nearly 2 decades ago, Irving Gottesman (2001) pointedly suggested that no discipline committed to understanding any of the major disorders (insert Alzheimer’s disease in this example) has a monopoly on the amounts of uncertainty that remain for current and future generations of investigators. By joining forces across disciplines and assembling the most certain and important facts, investigators can launch new initiatives not previously imagined. Such an effort will be required to solve the complex puzzle of Alzheimer’s disease.

Acknowledgments

This work was supported by National Institutes of Health grants P50 AG05131 (M.W.B., D.P.S.), R01 AG049810 (M.W.B.) and K24 AG026431 (M.W.B.), and the U.S. Department of Veterans Affairs Clinical Sciences Research and Development Service (Career Development Award-2 1IK2 CX001415-01A1 to E.C.E.). Dr. Salmon serves as a consultant for Bristol-Myers Squibb. Dr. Bondi serves as a consultant for Novartis and Eisai and receives royalties from Oxford University Press.

The other authors report no disclosures.

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In the U.S. and around the world, inflation is high and getting higher

Two years ago, with millions of people out of work and central bankers and politicians striving to lift the U.S. economy out of a pandemic-induced recession , inflation seemed like an afterthought. A year later, with unemployment falling and the inflation rate rising, many of those same policymakers insisted that the price hikes were “transitory” – a consequence of snarled supply chains, labor shortages and other issues that would right themselves sooner rather than later.

Now, with the inflation rate higher than it’s been since the early 1980s, Biden administration officials acknowledge that they  missed their call . According to the latest report from the Bureau of Labor Statistics, the annual inflation rate in May was 8.6%, its highest level since 1981, as measured by the consumer price index . Other  inflation metrics  also have shown significant increases over the past year or so, though not quite to the same extent as the CPI.

With inflation in the United States running at its highest levels in some four decades, Pew Research Center decided to compare the U.S. experience with those of other countries, especially its peers in the developed world. An earlier version of this post was published in November 2021.

The Center relied primarily on data from the Organization for Economic Cooperation and Development (OECD), most of whose 38 member states are highly developed democracies. The OECD collects a  wide range of data  about its members, facilitating cross-national comparisons. We chose to use quarterly inflation measures, both because they’re less volatile than monthly figures and because they were available for all but one OECD country (Costa Rica, which joined the OECD in May 2021). Quarterly inflation data also were available for seven non-OECD countries with sizable national economies, so we included them in the analysis as well.

For each country, we calculated year-over-year inflation rates going back to the first quarter of 2010 and ending in the first quarter of this year. We also calculated how much those rates had risen or fallen since the start of the COVID-19 pandemic in the first quarter of 2020.

To get a sense of longer-term inflation trends in the U.S., we analyzed two measures besides the commonly cited consumer price index: The  Consumer Price Index Retroactive Series  (R-CPI-U-RS) from the Bureau of Labor Statistics, and the  Personal Consumption Expenditures Price Index  from the Bureau of Economic Analysis.

Inflation in the United States was relatively low for so long that, for entire generations of Americans, rapid price hikes may have seemed like a relic of the distant past. Between the start of 1991 and the end of 2019, year-over-year inflation averaged about 2.3% a month, and exceeded 5.0% only four times. Today, Americans rate inflation as the  nation’s top problem , and President Joe Biden has said addressing the problem is his top domestic priority .

But the U.S. is  hardly the only place  where people are experiencing inflationary whiplash. A Pew Research Center analysis of data from 44 advanced economies finds that, in nearly all of them, consumer prices have risen substantially since pre-pandemic times.

In 37 of these 44 nations, the average annual inflation rate in the first quarter of this year was at least twice what it was in the first quarter of 2020, as COVID-19 was beginning its deadly spread. In 16 countries, first-quarter inflation was more than four times the level of two years prior. (For this analysis, we used data from the Organization for Economic Cooperation and Development, a group of mostly highly developed, democratic countries. The data covers 37 of the 38 OECD member nations, plus seven other economically significant countries.)

Among the countries studied, Turkey had by far the highest inflation rate in the first quarter of 2022: an eye-opening 54.8%. Turkey has experienced high inflation for years, but it shot up in late 2021 as the government pursued  unorthodox economic policies , such as cutting interest rates rather than raising them.

The country where inflation has grown  fastest  over the past two years is Israel. The annual inflation rate in Israel had been below 2.0% (and not infrequently negative) every quarter from the start of 2012 through mid-2021; in the first quarter of 2020, the rate was 0.13%. But after a relatively mild recession , Israel’s consumer price index began rising quickly: It averaged 3.36% in the first quarter of this year, more than 25 times the inflation rate in the same period in 2020.

Besides Israel, other countries with very large increases in inflation between 2020 and 2022 include Italy, which saw a nearly twentyfold increase in the first quarter of 2022 compared with two years earlier (from 0.29% to 5.67%); Switzerland, which went from ‑0.13% in the first quarter of 2020 to 2.06% in the same period of this year; and Greece, a country that knows something about economic turbulence . Following the Greek economy’s near-meltdown in the mid-2010s, the country experienced several years of low inflation – including more than one bout of deflation, the last starting during the first spring and summer of the pandemic. Since then, however, prices have rocketed upward: The annual inflation rate in Greece reached 7.44% in this year’s first quarter – nearly 21 times what it was two years earlier (0.36%).

Annual U.S. inflation in the first quarter of this year averaged just below 8.0% – the 13th-highest rate among the 44 countries examined. The first-quarter inflation rate in the U.S. was almost four times its level in 2020’s first quarter.

Regardless of the absolute level of inflation in each country, most show variations on the same basic pattern: relatively low levels before the  COVID-19 pandemic  struck in the first quarter of 2020; flat or falling rates for the rest of that year and into 2021, as many governments sharply curtailed most economic activity; and rising rates starting in mid- to late 2021, as the world struggled to get back to something approaching normal.

But there are exceptions to that general dip-and-surge pattern. In Russia, for instance, inflation rates rose steadily throughout the pandemic period before surging in the wake of its invasion of Ukraine . In Indonesia, inflation fell early in the pandemic and has remained at low levels. Japan has continued its years-long struggle with inflation rates that are too  low . And in Saudi Arabia, the pattern was reversed: The inflation rate surged  during  the pandemic but then fell sharply in late 2021; it’s risen a bit since, but still is just 1.6%.

Inflation doesn’t appear to be done with the developed world just yet. An  interim report  from the OECD found that April’s inflation rate ran ahead of March’s figure in 32 of the group’s 38 member countries.

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