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Midlife Serum Cholesterol and Increased Risk of Alzheimer's and Vascular Dementia Three Decades Later- pdf attached
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Dement Geriatr Cogn Disord Aug 4 2009;28:75-80
Alina Solomon a, b Miia Kivipelto a, b Benjamin Wolozin c Jufen Zhou d Rachel A. Whitmer d
a Department of Neurology, University of Kuopio, Kuopio , Finland; b Aging Research Center, Karolinska Institutet,
Stockholm , Sweden; c Department of Pharmacology, Boston University School of Medicine, Boston, Mass. , and
d Division of Research, Kaiser Permanente, Oakland, Calif. , USA
"This is the first study to specifically investigate the relationship between midlife serum total cholesterol levels and the risk of AD and VaD 3 decades later in a large and very diverse cohort of both women and men. After controlling for a wide range of confounders, midlife cholesterol was associated with both AD and VaD in late life.
dementia and cardiovascular disease are common major health problems, share several risk factors and often occur simultaneously, interacting with one another. Effective management of such disorders thus warrants a transdisciplinary approach.
High cholesterol levels as defined by the 2002 ATP III guidelines ( 6 240 mg/dl) [12] represented a significant risk factor for AD as well, besides the well-known connection to cardiovascular disease risk. Cholesterol values '250 mg/dl have been previously linked to an increased risk of dementia/AD in the Finnish population (CAIDE study, Finnish cohorts of the Seven Countries Study) [2, 3] . The results of the present study point to an even lower threshold, as additional analyses with cholesterol levels categorized into quartiles indicated that midlife cholesterol values '220 mg/dl increase the risk of developing AD 3 decades later. Therefore, even moderately elevated cholesterol in midlife was associated with an increased risk of AD.
Several mechanisms may lie behind the cholesterol- AD association. One hypothesis would indicate the vascular pathway, since high serum cholesterol is related to cardiovascular and cerebrovascular conditions, which have been linked to AD. However, the relation between high midlife serum total cholesterol and AD was significant in our study even after controlling for several vascular factors and conditions, suggesting that there might be other mechanisms as well. A key component for brain function, cholesterol turnover has also been associated with neurodegenerative diseases [15] . Due to the bloodbrain barrier, serum and brain cholesterol are 2 separate pools, but they do interact, for example through 24- and 27-hydroxycholesterol [15] ."
Aims: To investigate midlife cholesterol in relation to Alzheimer's disease (AD) and vascular dementia (VaD) in a large multiethnic cohort of women and men. Methods: The Kaiser Permanente Northern California Medical Group (healthcare delivery organization) formed the database for this study. The 9,844 participants underwent detailed health evaluations during 1964-1973 at ages 40-45 years; they were still members of the health plan in 1994. AD and VaD were ascertained by medical records between 1 January 1994 and 1 June 2007. Cox proportional hazards models - adjusted for age, education, race/ethnic group, sex, midlife diabetes, hypertension, BMI and late-life stroke - were conducted. Results: In total, 469 participants had AD and 127 had VaD. With desirable cholesterol levels (<200 mg/dl) as a reference, hazard ratios (HR) and 95% CI for AD were 1.23 (0.97-1.55) and 1.57 (1.23-2.01) for borderline (200-239 mg/dl) and high cholesterol (ge240 mg/dl), respectively. HR and 95% CI for VaD were 1.50 (1.01-2.23) for borderline and 1.26 (0.82-1.96) for high cholesterol. Further analyses for AD (cholesterol quartiles, 1st quartile reference) indicated that cholesterol levels >220 mg/dl were a significant risk factor: HR were 1.31 (1.01-1.71; 3rd quartile, 221-248 mg/dl) and 1.58 (1.22-2.06; 4th quartile, 249-500 mg/dl). Conclusion: Midlife serum total cholesterol was associated with an increased risk of AD and VaD. Even moderately elevated cholesterol increased dementia risk. Dementia risk factors need to be addressed as early as midlife, before underlying disease(s) or symptoms appear.
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