Lifetime risk of dementia and Alzheimer's disease: The impact of mortality on risk estimates in the Framingham Study
Abstract
We estimated the remaining lifetime risks of developing Alzheimer's disease (AD) and dementia from all causes, based on data from longitudinal population studies. The risk of developing AD during one's lifetime depends on both disease incidence and life expectancy. Conventional estimates of cumulative incidence overestimate the risk when there is a substantial probability of mortality due to competing causes. A total of 2,611 cognitively intact subjects (1,061 men, 1,550 women; mean age, 66 +/- 7 years) were prospectively evaluated for the development of AD or other dementia. A modified survival analysis was used to estimate both cumulative incidence and the sex-specific remaining lifetime risk estimates for quinquennial age groups above age 65 years. Over a 20-year follow-up period, 198 subjects developed dementia (120 with AD). The remaining lifetime risk of AD or other dementia depended on sex, being higher in women, but varied little with age between 65 and 80 years. In a 65-year-old man, the remaining lifetime risk of AD was 6.3% (95% CI, 3.9 to 8.7) and the remaining lifetime risk of developing any dementing illness was 10.9% (95% CI, 8.0 to 13.8); corresponding risks for a 65-year-old woman were 12% (95% CI, 9.2 to 14.8) and 19% (95% CI, 17.2 to 22.5). The cumulative incidence between age 65 and 100 years was much higher: for AD, 25.5% in men and 28.1% in women; for dementia, 32.8% in men and 45% in women. The actual remaining lifetime risk of AD or dementia varies with age, sex, and life expectancy and is lower than the hypothetical risk estimated by a cumulative incidence in the same population.
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A study using Framingham Heart Study data suggested that men in the study appeared to have a lower risk for dementia due to survival bias.
“A study using Framingham Heart Study data suggested that men in the study appeared to have a lower risk for dementia due to “survival bias,” in which the men who survived to age 65 or beyond and were included in the study were the ones with a healthier cardiovascular risk profile (men have a higher rate of death from cardiovascular disease in middle age than women) and thus a lower risk for dem”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [288]
Women live longer than men on average, and older age is the greatest risk factor for Alzheimer's.
“Women live longer than men on average, and older age is the greatest risk factor for Alzheimer's.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [288]
The rate of progression from MCI to AD is similar in men and women aged 70-79, but higher in women than men after age 80.
“According to a Mayo Clinic study on aging, the progression from mild cognitive impairment (MCI) to AD was similar in men and women in the ages of 70–79, but higher in women than men after 80 years of age.”
From Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human (2020) · cites this paper as [40]
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Background
- Authors
- Seshadri, S., Wolf, P. A., Beiser, A., Au, R., McNulty, K., White, R., & D'Agostino, R. B.
- Affiliations
- Boston University (US)
- Venue
- Neurology
- Published
- 1997-12
- Volume
- 49
- Issue
- 6
- Pages
- 1498-1504
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2007172048
- Cited by
- 489
- References
- 22
- Citations by year
- 2026: 18 · 2025: 41 · 2024: 38 · 2023: 32 · 2022: 45 · 2021: 33 · 2020: 31 · 2019: 35 · 2018: 32 · 2017: 17 · 2016: 18 · 2015: 17 · 2014: 16 · 2013: 17 · 2012: 10
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc038038-022)
- National Institute on Aging (5-RO1-AG08122-08, R01AG008122)
- National Heart, Lung, and Blood Institute (N01-HC-38038)
- National Institute of Neurological Disorders and Stroke (R01NS017950)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- Alzheimer's disease, dementia, cumulative incidence, competing risks, mortality, sex differences, life expectancy, older adults, survival analysis
- MeSH terms
- Aged, Alzheimer Disease, Dementia, Female, Humans, Male, Middle Aged, Mortality, Risk Factors, Time Factors
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