Alzheimer's Linked to Cholesterol Level in Middle Age

By Crystal Phend, Senior Staff Writer, MedPage Today
Published: August 04, 2009

Action Points

* Explain to interested patients that cholesterol levels are an important marker of cardiovascular health and may likewise be linked to dementia risk.


* Note that the retrospective observational study suggested a temporal relationship but could not determine causality.

Even modestly elevated cholesterol in midlife portends greater Alzheimer's disease risk in old age, researchers found.

Above average cholesterol of 220 mg/dl or higher at age 40 to 45 raised the risk 31% to 58% for Alzheimer's diagnosis in the next three decades, compared with low cholesterol, Alina Solomon, MD, of the University of Kuopio, Finland, and colleagues reported in the August issue of Dementia & Geriatric Cognitive Disorders.

These results suggested a lower threshold for risk than some prior studies, the researchers noted.

Cholesterol over 250 mg/dl in middle age elevated Alzheimer's disease risk in the CAIDE study and Finnish cohort of the Seven Countries Study, although it has not been linked over a broader time course in other studies, including the Framingham study.

Rather than waiting to address dementia symptoms as they arise with age, the results support a shift toward earlier attention, the researchers wrote. That means "addressing risk factors as early as midlife, before the underlying disease(s) or the symptoms appear."

Effective management requires a cross-disciplinary approach to lifestyle changes, added co-author Rachel Whitmer, PhD, of Kaiser Permanente in Oakland, Calif.

The researchers analyzed the longitudinal electronic medical record databases of Kaiser Permanente of Northern California.

The cohort included members of the health maintenance organization who had completed detailed health evaluations as part of a "multiphasic" well-care initiative in the organization from 1964 through 1973, when they were ages 40 to 45.

Overall, 9,844 individuals remained members through at least 1994, after which dementia ascertainment started.

In the cohort, cholesterol levels of at least 240 mg/dl during their 40s -- considered high by Adult Treatment Panel (ATP) III guidelines -- were associated with 57% elevated Alzheimer's disease risk three decades later (HR 1.57, 95% CI 1.23 to 2.01).

Cholesterol levels considered borderline (200 to 239 mg/dl) showed a more modest trend for increased Alzheimer's risk compared with cholesterol under 200 mg/dl (HR 1.23, 95% CI 0.97 to 1.55).

Interestingly, the opposite was true for the second most common type of dementia.

Borderline-elevated cholesterol at age 40 to 45 significantly predicted elevated vascular dementia risk (HR 1.50, 95% CI 1.01 to 2.23), whereas frank hypercholesterolemia did not (HR 1.26, 95% CI 0.82 to 1.96).

Further refining the analysis by quartiles of cholesterol at midlife revealed a significant link for both above-average groups compared with the lowest quartile (cholesterol levels under 198 mg/dl).

Those in the top quartile (249-mg/dl-and-over) quartile were at 58% higher Alzheimer's risk (95% CI 1.22 to 2.06), while those in the quartile with 221-248 mg/dl cholesterol were at 31% elevated risk (95% CI 1.01 to 1.71).

The researchers noted that the vascular dementia findings were based on relatively few events and that the study did not include data on subtypes of cholesterol or use of lipid-lowering therapy.

However, because the initial cholesterol measurements were collected at a time in life when Alzheimer's disease and other forms of dementia would be unlikely, the results suggested a temporal association.

The mechanism for it may have been vascular since serum cholesterol is related to both cardiovascular and cerebrovascular conditions, which have been in turn been linked to Alzheimer's disease.

But the researchers noted that their findings were significant even after adjustment for major vascular factors and conditions.

Other possible pathways might be cholesterol turnover in the brain, which has been associated with neurodegenerative diseases, they said.

Cholesterol plays a key function in the brain and, while it does not cross the blood-brain barrier, stores of it in the serum and brain do interact.

The authors noted that "about 60 to 70% of the total serum cholesterol is typically represented by LDL cholesterol, the major atherogenic lipoprotein. However, the role of LDL as a risk factor for AD or VaD could not be investigated in this study because data on LDL levels in 1964 to 1973 was not available."