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

Mielke, Michelle M.; Zandi, Peter P.; Shao, Huibo; Wærn, Margda; Östling, Svante; Guo, Xinxin; Björkelund, Cecilia; Lissner, Lauren; Skoog, Ingmar; Gustafson, Deb

doi:10.1212/wnl.0b013e3181feb2bf

Cited by 133 publications

(125 citation statements)

References 28 publications

(43 reference statements)

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“…The association between plasma lipoprotein profiles and risk of development of clinical manifestations of dementia has been controversial. An association between high cholesterol levels in midlife and an increased risk for dementia in old age has been suggested by several publications [68], but it was not confirmed by a recent large population study [69]. Instead, this study found that low cholesterol levels in late life were predictive of subsequent dementia.…”

Section: Alzheimer Diseasecontrasting

confidence: 81%

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

Sena¹,

Capela²,

Nóbrega³

et al. 2012

Lipoproteins - Role in Health and Diseases

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Section: Alzheimer Diseasecontrasting

confidence: 81%

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

Sena¹,

Capela²,

Nóbrega³

et al. 2012

Lipoproteins - Role in Health and Diseases

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“…The older age of the current sample may again partially explain these findings because the presence of these factors during midlife appears to represent the critical risk window for developing AD, and this risk is attenuated or reversed in late-life possibly due to survival bias (21,(53)(54)(55)(56)(57)(58)(59)(60) and the increased prevalence of these conditions with aging. When examined as a continuous variable, PP has previously been found to be unrelated to the clinical diagnosis of AD in a sample of !75 year olds, and other studies have also failed to find an association between antemortem PP and ADNP severity (10,20).…”

Section: Discussionmentioning

confidence: 85%

Late-Life Vascular Risk Factors and Alzheimer Disease Neuropathology in Individuals with Normal Cognition

Besser

Alosco

Gómez

et al. 2016

J Neuropathol Exp Neurol

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Vascular risk factors (VRFs) have been associated with clinically diagnosed Alzheimer disease (AD), but few studies have examined the association between VRF and AD neuropathology (ADNP) in cognitively normal individuals. We used longitudinal data from the National Alzheimer's Disease Center's Uniform Data Set and Neuropathology Data Set to examine the association between VRF and ADNP (moderate to frequent neuritic plaques; Braak stage III-VI) in those with normal cognition. Our sample included 53 participants with ADNP and 140 without ADNP. Body mass index (BMI), resting heart rate (HR), and pulse pressure (PP) were measured at each visit; values were averaged across participant visits and examined annual change in BMI, PP, and HR. Hypertension, diabetes, and hypercholesterolemia were self-reported. In the multivariable logistic regression analyses, average BMI and HR were associated with lower odds of ADNP, and annual increases in HR and BMI were associated with higher odds of ADNP. A previously experienced decline in BMI or HR in late-life (therefore, currently low BMI and low HR) as well as a late-life increase in BMI and HR may indicate underlying AD pathology. Additional clinicopathological research is needed to elucidate the role of changes in late-life VRF and AD pathogenesis.

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“…Many case -control studies have also confirmed that mild hypercholesterolemia accompanies late-onset AD [49,62,63]. However, a 32-year long follow-up study of 1462 women has failed to find an association of mid-life hypercholesterolemia with increasing risk of AD, and even some studies have indicated that a high blood cholesterol especially in latelife is actually protective against AD [64,65,66]. The statin group of cholesterol lowering agents has been shown to produce beneficial effects in AD subjects in some studies [67].…”

Section: Metabolic Risk Factors Of Ad: Present Statusmentioning

confidence: 99%

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

Chakrabarti¹,

Khemka²,

Banerjee³

et al. 2015

Aging and disease

111

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Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, proinflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors.

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

Cited by 133 publications

References 28 publications

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

Plasma Lipoproteins in Brain Inflammatory and Neurodegenerative Diseases

Late-Life Vascular Risk Factors and Alzheimer Disease Neuropathology in Individuals with Normal Cognition

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

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