Defining Alzheimer's Disease

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Alzheimer's disease is a progressive neurodegenerative brain disease, gradually erasing core elements of the self and interaction with others before eventually claiming what is required to sustain life.

Worldwide, it is the most common cause of the constellation of gradual decline in memory, thinking, behavior, and social skills that defines dementia.

Epidemiology

Alzheimer's disease accounts for approximately 60-80% of dementia cases and affects 4.8-6.9 million Americans. Those estimates are believed to be low, however, because the disease is likely underdiagnosed.

The numbers of people with Alzheimer's disease and related dementias (incidence) are rapidly rising due to the aging of society, but prevalence (cases per 100,000) is declining. The Chicago Health and Aging Project (CHAP) study's door-to-door census in Chicago showed an average annual incidence of Alzheimer's dementia in 2011 among people ages 65-74 of 0.4%, 3.2% among those 75-84, and 7.6% in those 85 and older. But the overall incidence fell from 2.8% in 1998-2000 to 2.2% in 2004-2006 and held steady in 2010-2012.

And in the Health and Retirement Study, for example, the age-adjusted prevalence of dementia overall decreased from 12.2% in 2000 to 8.5% in 2016 among those age 65 and older -- a relative 30.1% decline. The researchers found that an increase in the level of education explained much of the shift, along with improvement in other modifiable risk factors, such as better prevention and treatment of hypertension.

However, increasing age is the biggest known risk factor for Alzheimer's disease and other dementias. More than 70% of people with Alzheimer's disease are 75 years or older.

Thus the rising proportion of the population ages 65 and older is expected to double the prevalence of Alzheimer's cases by 2050.

CHAP pointed to an 11.3% prevalence of clinical Alzheimer's adjusted to 2020 U.S. census figures. The lowest rate (10.0%) was among non-Hispanic white adults, rising to 14.0% among Hispanic and 18.6% among non-Hispanic African-American adults. But as the population ages over time, that 6.07 million people living with clinical Alzheimer's disease was projected to increase to 13.85 million in 2060.

Still, the Alzheimer's Association's annual facts and figures document noted: "It is unclear whether these encouraging declines in incidence will continue. For example, worldwide increases in diabetes and obesity, which are risk factors for dementia, among people younger than 65 may lead to a rebound in dementia risk in coming years."

Defining Alzheimer's

Characteristic of Alzheimer's dementia is build-up of toxic species of amyloid and tau proteins that form plaques and tangles that make the brain cells around them die. The brain atrophies and loss of connections between neurons in the brain hampers communication both from one area of the brain to another and out to muscles and organs.

In 2018, the National Institute on Aging and the Alzheimer's Association published a research framework with a biological rather than clinical signs or symptoms-based definition of the disease based on AT(N) classification:

• Presence of amyloid pathology (A)

• Tau pathology (T)

• Neuronal injury (N)

Amyloid pathology together with either tau pathology or neuronal injury or both is required to indicate Alzheimer's under that research framework, although not for routine clinical use.

In 2022, an International Working Group responded with recommendations for a combined clinical and biological approach to diagnosis, which it recommended "be restricted to people who have positive biomarkers together with specific Alzheimer's disease phenotypes, whereas biomarker-positive cognitively unimpaired individuals should be considered only at-risk for progression to Alzheimer's disease."

Recently, an Alzheimer's Association workgroup released a revised disease staging system and new biologically based criteria that define the disease as a process detectable by abnormal biomarkers when patients do not yet have cognitive symptoms. However, the workgroup cautioned that their document should not be considered clinical practice guidelines and that testing cognitively unimpaired individuals outside of research studies remains not recommended.

Formal clinical practice guidelines around treatment and testing are expected from the Alzheimer's Association in the near future.

Distinguishing Dementias

The umbrella term "dementia" covers many different diagnoses with characteristic symptoms of problems with memory, language, problem-solving, and other thinking skills that impact the activities of daily life.

While Alzheimer's disease dominates as the most common dementia, other less common types of dementia include:

• Vascular dementia -- often due to an ischemic stroke (estimated to make up 5-10% of all dementias)

• Hippocampal sclerosis (3-13%)

• Lewy body dementia (5%)

• Frontotemporal dementia, or frontotemporal lobar degeneration (3%)

• Parkinson's disease (3.6%)

Mixed pathologies are quite common, particularly after age 85. Studies have found that more than half of people with Alzheimer's dementia have pathophysiology of another type of dementia as well. In one autopsy study, Alzheimer's brain pathology was the sole pathology in only 3% of 447 older people believed to have Alzheimer's dementia when they died, whereas 15% had the brain changes of a different cause of dementia and 82% had Alzheimer's and another dementia pathology.

"Mixed dementia may also account for the wide variety of memory and thinking problems experienced by people living with dementia," according to the Alzheimer's Association. "It is currently not possible to determine with certainty which symptoms are due to which dementia."

Up next: Pathogenesis and Genetics of Alzheimer's Disease