A claim you hear on longevity podcasts

Can you have Alzheimer's plaques without dementia?

The claim checked: Perhaps 20 to 30% of older people without dementia have Alzheimer's changes in the brain Hear it at 2:00:25

What do the studies say?

Leaning for

Three studies put the share close to that range. One found 22.0% of adults aged 50 to 89 without dementia had amyloid, the protein in Alzheimer's plaques. Six found the share depends on age and on the test. It ran from 21% at the strictest bar to 59% of healthy adults by age 89.

Computed from 9 studies that test this point, each judged by two readers, in full. 10 more studies are waiting for a full read and do not count yet.

What was said on the podcast?

“it turns out that perhaps 20 to 30% of these individuals who never had dementia have Alzheimer pathology.”
Masud Husain, a guest on Huberman Lab · How to Improve Motivation & Overcome Procrastination | Dr. Masud Husain · 2:00:25 on YouTube
The point checked Leaning for

Perhaps 20 to 30% of older people who never had dementia have Alzheimer's pathology (amyloid plaques and tau tangles) in their brains

Agree 3

pooled analysis · 2015 · landmark

“The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI.”

Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA
Who: Individual participant data from 55 PET/CSF biomarker studies: 2914 participants with normal cognition, 697 with subjective cognitive impairment and 3972 with MCI, aged 18 to 100 years
PMID 25988462

other primary study · 2009 · landmark

“First, consistent with previous reports, a substantial proportion of nondemented older adults were found to have npAD, with the frequency ranging from about 20% (when criteria are restricted to Probable/Definite CERAD and Intermediate/High NIA-Reagan) to about 40% (all levels of criteria).”

Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease. Neurobiol Aging
Who: 97 autopsied nondemented participants (CDR 0 within 2 years of death) aged 60 or older at death (mean 84 years) from 7 Alzheimer's Disease Centers
PMID 19376612

other primary study · 2018 · landmark

“The total prevalence of amyloid positivity across all ages was 22.0% (18.9% to 30.5%).”

Prevalence and Outcomes of Amyloid Positivity Among Persons Without Dementia in a Longitudinal, Population-Based Setting. JAMA Neurol
Who: Population-based Olmsted County, Minnesota adults aged 50-89 without dementia (Mayo Clinic Study of Aging), 98% white, mean age 71.3
PMID 29710225

Partly agree 6

other primary study · 2014 · landmark

“We estimate that from age 50-60 the frequency of pre-clinical AD (asymptomatic at risk for AD) is close to zero, and by age 89 over half (59%) of the cognitively normal general population will meet these criteria”

Age-specific population frequencies of cerebral β-amyloidosis and neurodegeneration among people with normal cognitive function aged 50-89 years: a cross-sectional study. Lancet Neurol
Who: 985 cognitively normal people aged 50 to 89 from the population-based Mayo Clinic Study of Aging (Olmsted County, Minnesota) with amyloid PET, FDG PET and MRI
PMID 25201514

other primary study · 2017 · landmark

“By age 85 over 90% of men and women have one or more biomarker abnormalities.”

Age-specific and sex-specific prevalence of cerebral β-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50-95 years: a cross-sectional study. Lancet Neurol
Who: Clinically normal participants aged 50-95 in the population-based Mayo Clinic Study of Aging: 435 with amyloid PET, tau PET and MRI plus 1113 with amyloid PET and MRI only
PMID 28456479

other primary study · 2012

“Frequency of pAD pathology progresses from stage 1 or greater (n = 53; 43%) to stage 2 or greater (n = 41; 33%), to stage 3 (n = 26; 21%).”

Preclinical AD Workgroup staging: pathological correlates and potential challenges. Neurobiol Aging
Who: 126 cognitively intact older adults from the University of Kentucky ADC cohort autopsied within a year of last cognitive testing (mean age at death 83.7 years); 24 MCI and 14 early AD cases for comparison
PMID 21507528

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other primary study · 2026

“Among non-demented subjects, 28% would have displayed moderate to high levels of Aβ and 21% moderate to high levels of HPτ.”

Incidence of altered proteins in the aging brain: Implications for biological diagnostic markers. J Alzheimers Dis
Who: 1825 autopsied subjects aged 50-102 at death in the Uppsala region, Sweden; 1453 without clinical dementia (mean age at death 75), dementia status taken from referral charts
PMID 41636369

other primary study · 2016

“We evaluated the association of low and high Braak scores upon cognitive domains and plaque pathology in a large cohort of elderly persons without cognitive impairment.”

Braak staging, plaque pathology, and APOE status in elderly persons without cognitive impairment. Neurobiol Aging
Who: 123 autopsied Rush Religious Orders Study participants with no cognitive impairment at last evaluation (mean age at death 83.9), excluding strokes, Lewy body disease and other mixed pathologies
PMID 26686670

other primary study · 2021

“Our work indicates that a substantial proportion of nondemented older individuals could have high degrees of amyloidosis, tauopathy, and neurodegeneration but not develop dementia during life.”

Theoretical impact of the AT(N) framework on dementia using a community autopsy sample. Alzheimers Dement
Who: 603 autopsied participants of the community-based Adult Changes in Thought study (Kaiser Permanente Washington), enrolled at age 65+, with known dementia status at death; 398 dementia-free 5 years before death
PMID 33900044

Disagree 0

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