TY - JOUR
T1 - The 32-year relationship between cholesterol and dementia from midlife to late life
AU - Mielke, M. M.
AU - Zandi, P. P.
AU - Shao, H.
AU - Waern, M.
AU - Östling, S.
AU - Guo, X.
AU - Björkelund, C.
AU - Lissner, L.
AU - Skoog, I.
AU - Gustafson, D. R.
N1 - Funding Information:
Study funding: Supported by the NIH ( NIA 1R03AG026098-01A1, NIA 1R21AG028754 , and NINDS R21NS060271-01 ), the Swedish Research Council ( 11267 and 2005-8460 ), the Swedish Brain Power Project, EU FP7 project LipiDiDiet ( 211696 ), Swedish Council for Working Life and Social Research ( 1154 ), FAS EpiLife ( 2006–1506 ), Swedish Alzheimer Association, Stiftelsen Söderström-Königska Sjukhemmet, Stiftelsen för Gamla Tjänarinnor, Hjalmar Svenssons Foundation, The Swedish Society of Medicine, The Göteborg Medical Society, the Lions Foundation, the Dr. Felix Neubergh Foundation, the Wilhelm and Martina Lundgren Foundation, the Elsa and Eivind Kison Sylvan Foundation, and the Alzheimer's Association Zenith Award ( ZEN-01-3151 ).
Funding Information:
Dr. Mielke receives research support from the NIH ( R21 NS06027-01 [PI ], R21 AG028754 [PI] , and R01 AG21136 [Investigator]) and from the George and Cynthia Mitchell Foundation . Dr. Zandi receives research support from the NIH ( NIMH K01 MH072866-01 [PI], NIMH R01 MH083738-01 [PI], NIA BJ18-JHU-ARRA [sub-contract PI], R01MH076953 [Coinvestigator], R37AA12303 [Coinvestigator], R01MH079240 [Coinvestigator], NIMH K99MH086049-01A1 [Co-mentor], R37DA011796 [Coinvestigator], and NIMH R01 MH 42243 [Coinvestigator]). Mr. Shao reports no disclosures. Dr. Waern receives research support from the Swedish Research Council and the Swedish Council for Working Life and Social Research. Dr. Östling receives research support from Stiftelsen Söderström-Königska Sjukhemmet. Dr. Guo reports no disclosures. Dr. Bjorkelund serves on scientific advisory boards for LifeGene Sweden and the Swedish Council on Health Technology Assessment; serves as an Associate Editor for the Scandinavian Journal of Primary Health Care; and receives research support from the Swedish Council for Working Life and Social Research. Dr. Lissner reports no disclosures. Dr. Skoog has served on scientific advisory boards for Pfizer Inc. and AstraZeneca; has served on an editorial advisory board for International Psychogeriatrics; receives royalties from publishing Alzheimers sjukdom och andra kognitiva sjukdomar (English title: Alzheimer's Disease and Other Cognitive Disorders [Liber, 2003]); serves on speakers' bureaus for Shire plc, Janssen-Cilag, Pfizer Inc., Novartis, and Esai Inc.; and has received research support from the Swedish Research Council, Swedish Council for Working Life and Social Research, the Alzheimer's Association, and the Bank of Sweden Tercentenary Foundation. Dr. Gustafson serves as a consultant for the Albuquerque Area Indian Health Board; has served on the speakers' bureau for Shire plc; and receives research support from the NIH ( NIA 5R03AG026098 [PI]) and the Swedish Research Council .
PY - 2010/11/23
Y1 - 2010/11/23
N2 - 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.
AB - 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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U2 - 10.1212/WNL.0b013e3181feb2bf
DO - 10.1212/WNL.0b013e3181feb2bf
M3 - Article
C2 - 21068429
AN - SCOPUS:78650001684
VL - 75
SP - 1888
EP - 1895
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 21
ER -