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Relation of Left Ventricular Ejection Fraction to Cognitive Aging (from the Framingham Heart Study)

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Heart failure is a risk factor for Alzheimer's disease and cerebrovascular disease. In the absence of heart failure, it was hypothesized that left ventricular ejection fraction (LVEF), an indicator of cardiac dysfunction, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected from 1,114 Framingham Heart Study Offspring Cohort participants free from clinical stroke or dementia (aged 40 to 89 years, mean age 67 ± 9 years, 54% women). Neuropsychological and neuroimaging markers of brain aging were related to cardiac MRI–assessed LVEF. In multivariable-adjusted linear regressions, LVEF was not associated with any brain aging variable (p values >0.15). However, LVEF quintile analyses yielded several U-shaped associations. Compared to the referent (quintile 2 to 4), the lowest quintile (quintile 1) LVEF was associated with lower mean cognitive performance, including Visual Reproduction Delayed Recall (β = −0.27, p <0.001) and Hooper Visual Organization Test (β = −0.27, p <0.001). Compared to the referent, the highest quintile (quintile 5) LVEF values also were associated with lower mean cognitive performance, including Logical Memory Delayed Recall (β = −0.18, p = 0.03), Visual Reproduction Delayed Recall (β = −0.17, p = 0.03), Trail Making Test Part B − Part A (β = −0.22, p = 0.02), and Hooper Visual Organization Test (β = −0.20, p = 0.02). Findings were similar when analyses were repeated excluding prevalent cardiovascular disease. In conclusion, although these observational cross-sectional data cannot establish causality, they suggest a nonlinear association between LVEF and measures of accelerated cognitive aging.

Section snippets

Methods

The Framingham Offspring Study design and selection criteria have been described elsewhere.10 From 1971 to 1975, 5,124 participants were recruited and have been examined every 4 to 8 years since. Details on the derivation of the current sample are provided in Figure 1. The protocol was approved by the local institutional review board. Participants provided written informed consent before assessments.

Participants completed the following cognitive protocol, which was selected a priori to

Results

Clinical characteristics are listed in Table 1. Cardiac MRI, brain MRI, and neuropsychological descriptive variables are listed in Table 2. As a continuous variable, the LVEF was unrelated to any brain MRI or neuropsychological variable (Table 3). Findings were not altered when participants with CVD were excluded (Table 4).

When LVEF quintiles were compared to assess associations with brain aging variables, participants in quintile 1 did not differ from the referent group (quintiles 2 to 4) for

Discussion

Our epidemiologic findings suggest a U-shaped association, rather than a linear relation, between LVEF and markers of abnormal brain aging. Participants in the lowest and highest LVEF quintiles had cross-sectional evidence of abnormal cognitive changes compared to the middle referent group. The observation that a lower LVEF is associated with abnormal brain changes extends previous research examining patients with severe cardiomyopathies, which reported that a reduced LVEF was associated with

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    This study was supported by NHLBI's Framingham Heart Study N01-HC25195; AG027480, AG030962 (Paul B. Beeson Career Development Award in Aging Program), Alzheimer's Association IIRG-08-88733 (A.L.J.); P30-AG013846 (Boston University Alzheimer's Disease Core Center); AG08122, NS017950, AG033040, AG16495 (P.A.W.); AG028321, HL092577 (E.J.B.); AG033193, AG031287 (S.S.); AG021028 (CD), AG010129 (University of California, Davis, Alzheimer's Disease Core Center); and HL070279 (W.J.M.).

    Drs. Beiser and Benjamin contributed equally to this article.

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