The 32-year relationship between cholesterol and dementia from midlife to late life

Michelle M Mielke, P. P. Zandi, H. Shao, M. Waern, S. Östling, X. Guo, C. Björkelund, L. Lissner, I. Skoog, D. R. Gustafson

Research output: Contribution to journalArticle

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Abstract

Background: Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. Methods: The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38-60 years, was initiated in 1968-1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974-1975, 1980-1981, 1992-1993, and 2000-2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000-2001 examination. Results: Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94-8.43) among those who survived to and participated in the 2000-2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22-4.58). Conclusion: These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.

Original languageEnglish (US)
Pages (from-to)1888-1895
Number of pages8
JournalNeurology
Volume75
Issue number21
DOIs
StatePublished - Nov 23 2010
Externally publishedYes

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Dementia
Cholesterol
Alzheimer Disease
Hypercholesterolemia
National Institute of Neurological Disorders and Stroke
Confidence Intervals
Communication Disorders
Sweden
Diagnostic and Statistical Manual of Mental Disorders
Population
Prospective Studies

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Mielke, M. M., Zandi, P. P., Shao, H., Waern, M., Östling, S., Guo, X., ... Gustafson, D. R. (2010). The 32-year relationship between cholesterol and dementia from midlife to late life. Neurology, 75(21), 1888-1895. https://doi.org/10.1212/WNL.0b013e3181feb2bf

The 32-year relationship between cholesterol and dementia from midlife to late life. / Mielke, Michelle M; Zandi, P. P.; Shao, H.; Waern, M.; Östling, S.; Guo, X.; Björkelund, C.; Lissner, L.; Skoog, I.; Gustafson, D. R.

In: Neurology, Vol. 75, No. 21, 23.11.2010, p. 1888-1895.

Research output: Contribution to journalArticle

Mielke, MM, Zandi, PP, Shao, H, Waern, M, Östling, S, Guo, X, Björkelund, C, Lissner, L, Skoog, I & Gustafson, DR 2010, 'The 32-year relationship between cholesterol and dementia from midlife to late life', Neurology, vol. 75, no. 21, pp. 1888-1895. https://doi.org/10.1212/WNL.0b013e3181feb2bf
Mielke, Michelle M ; Zandi, P. P. ; Shao, H. ; Waern, M. ; Östling, S. ; Guo, X. ; Björkelund, C. ; Lissner, L. ; Skoog, I. ; Gustafson, D. R. / The 32-year relationship between cholesterol and dementia from midlife to late life. In: Neurology. 2010 ; Vol. 75, No. 21. pp. 1888-1895.
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abstract = "Background: Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. Methods: The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38-60 years, was initiated in 1968-1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974-1975, 1980-1981, 1992-1993, and 2000-2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000-2001 examination. Results: Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95{\%} confidence interval [CI] 0.94-8.43) among those who survived to and participated in the 2000-2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95{\%} CI 1.22-4.58). Conclusion: These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.",
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AU - Guo, X.

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