A Prospective Study of Alzheimer Disease in Down Syndrome
Abstract
Ninety-six individuals with Down syndrome over age 35 years were evaluated and followed up for evidence of nontreatable dementia. Dementia was judged to be present when a functional decline occurred in areas such as orientation, memory, verbal and motor skills, and self-care abilities. Forty-nine patients with Down syndrome fit this criterion, with an average onset of dementia at 54.2 +/- 6.1 years. The prevalence of dementia in the institutionalized Down syndrome population of our study (n = 53) was 8% (2/25 patients) between 35 and 49 years, 55% (11/20 patients) between 50 and 59 years, and 75% (6/8 patients) of those over 60 years old. Of note, 41 (84%) demented individuals with Down syndrome developed seizures. Ten (20%) had parkinsonian features. Adequately treated hypothyroidism was present in 27 (59%) of 46 demented patients with Down syndrome tested. The average duration of dementia in the 23 patients who died was 4.6 +/- 3.2 years. Computed tomographic scans in 43 patients all showed brain tissue loss, most pronounced in the temporal lobes. Brains from 12 autopsied cases showed large numbers of plaques and tangles in the same locations as in persons with Alzheimer disease.
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Virtually all people with full trisomy 21 are expected to develop the pathophysiological changes of Alzheimer's disease by their early to mid-40s.
“Because virtually all people with full trisomy 21 are expected to develop the pathophysiological changes of AD by their earyl to mid‐40's, this longitudinal design provides a unique opportunity to track physiological and cognitive changes through the clinically asymptomatic preclinical to the clinical stages of dementia.”
From The Alzheimer's Biomarker Consortium–Down Syndrome (ABC‐DS): A 10‐year report (2025) · cites this paper as [4]
Most adults with Down syndrome will have the neuropathologies characteristic of Alzheimer's disease by their early to mid-40s.
“In fact, most adults with DS will have the neuropathologies characteristic of AD by the time they reach their early to mid‐40s that anticipates further progression some years or decades later. 3 , 4 , 5 , 6”
From The Alzheimer's Biomarker Consortium–Down Syndrome (ABC‐DS): A 10‐year report (2025) · cites this paper as [4]
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- Authors
- Lai, F., & Williams, R. S.
- Affiliations
- Eunice Kennedy Shriver Center (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 1989-08-01
- Volume
- 46
- Issue
- 8
- Pages
- 849-853
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2104759359
- Cited by
- 561
- References
- 2
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 5 · 2023: 9 · 2022: 16 · 2021: 24 · 2020: 21 · 2019: 11 · 2018: 10 · 2017: 21 · 2016: 21 · 2015: 19 · 2014: 13 · 2013: 16 · 2012: 13
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 23973)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Down syndrome, Alzheimer's disease, dementia, dementia prevalence, age of onset, seizures, parkinsonian features, hypothyroidism, temporal lobe atrophy, functional decline, institutionalized patients
- MeSH terms
- Adult, Age Factors, Aged, Alzheimer Disease, Brain, Down Syndrome, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Seizures
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