Apolipoprotein E ϵ4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease

Kivipelto, Miia; Helkala, Eeva‐Liisa; Laakso, Mikko P.; Hänninen, Tuomo; Hallikainen, Merja; Alhainen, Kari; Iivonen, Susan; Mannermaa, Arto; Tuomilehto, Jaakko; Nissinen, Aulikki; Soininen, Hilkka

doi:10.7326/0003-4819-137-3-200208060-00006

Cited by 585 publications

(393 citation statements)

References 28 publications

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“…Additionally, 10 authors were contacted for missing or ambiguous information, of whom 7 responded. Two additional studies were found from cross-references [16,17], of which one could be included [16]. This resulted in 8 cross-sectional studies, 5 casecontrol studies, 10 prospective cohort studies and 1 study with both cross-sectional and prospective analyses (designated as cross-sectional regarding study quality).…”

Section: Resultsmentioning

confidence: 99%

“…Of those focusing on MI, four studies did not find an association with dementia, Alzheimer's disease, vascular dementia or decline to mild cognitive impairment or dementia [20][21][22][23]. Three studies did find a significant association between MI and dementia [18], Alzheimer's disease and Alzheimer's disease/ vascular dementia (but only for MI ascertained at the late-life visit) [16], and possible dementia/mild cognitive impairment [19]. Two out of the four AP studies did find that AP increased the risk of dementia or possible dementia/mild cognitive impairment [19,24], whereas the other two studies did not find an association [22,23].…”

Section: Prospective Cohort Studiesmentioning

confidence: 91%

“…From the eleven prospective cohort studies, seven focused on MI [16,[18][19][20][21][22][23], four on AP [19,[22][23][24], and four studies on the CHD compound [22,[25][26][27]. Of those focusing on MI, four studies did not find an association with dementia, Alzheimer's disease, vascular dementia or decline to mild cognitive impairment or dementia [20][21][22][23].…”

Section: Prospective Cohort Studiesmentioning

confidence: 99%

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[P3–542]: Coronary Heart Disease and Risk for Cognitive Impairment or Dementia: A Systematic Review and Meta‐analysis

Deckers

Schievink

Rodriquez

et al. 2017

Alzheimer's & Dementia

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Aims/HypothesisAccumulating evidence suggests an association between coronary heart disease and risk for cognitive impairment or dementia, but no study has systematically reviewed this association. Therefore, we summarized the available evidence on the association between coronary heart disease and risk for cognitive impairment or dementia. MethodsMedline, Embase, PsycINFO, and CINAHL were searched for all publications until 8 th January 2016. Articles were included if they fulfilled the inclusion criteria: (1) myocardial infarction, angina pectoris or coronary heart disease (combination of both) as predictor variable; (2) cognition, cognitive impairment or dementia as outcome; (3) population-based study; (4) prospective (!1 year follow-up), cross-sectional or case-control study design; (5) !100 participants; and (6) aged !45 years. Reference lists of publications and secondary literature were hand-searched for possible missing articles. Two reviewers independently screened all abstracts and extracted information from potential relevant full-text articles using a standardized data collection form. Study quality was assessed with the Newcastle-Ottawa Scale. We pooled estimates from the most fully adjusted model using random-effects metaanalysis. ResultsWe identified 6,132 abstracts, of which 24 studies were included. A meta-analysis of 10 prospective cohort studies showed that coronary heart disease was associated with increased risk of cognitive impairment or dementia (OR = 1.45, 95%CI = 1.21-1.74, p<0.001). Between-study heterogeneity was low (I 2 = 25.7%, 95%CI = 0-64, p = 0.207). Similar significant associations were found in separate meta-analyses of prospective cohort studies for the individual predictors (myocardial infarction, angina pectoris). In contrast, meta-analyses of cross-sectional and case-control studies were inconclusive. Funding: The author(s) received no specific funding for this work. Competing interests:The authors have declared that no competing interests exist. Conclusion/InterpretationThis meta-analysis suggests that coronary heart disease is prospectively associated with increased odds of developing cognitive impairment or dementia. Given the projected worldwide increase in the number of people affected by coronary heart disease and dementia, insight into causal mechanisms or common pathways underlying the heart-brain connection is needed.

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Section: Resultsmentioning

confidence: 99%

Section: Prospective Cohort Studiesmentioning

confidence: 91%

Section: Prospective Cohort Studiesmentioning

confidence: 99%

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[P3–542]: Coronary Heart Disease and Risk for Cognitive Impairment or Dementia: A Systematic Review and Meta‐analysis

Deckers

Schievink

Rodriquez

et al. 2017

Alzheimer's & Dementia

View full text Add to dashboard Cite

show abstract

“…Although a number of epidemiological studies have shown that hypercholesterolemia is related to an increased risk of developing AD or mild cognitive impairment (48)(49)(50), other results, which do not fit in with this conclusion, have also been reported. In 2005, for example, Reitz et al (51) observed no effects of cholesterol and triglyceride levels on the cognitive ability of aged individuals, while other studies demonstrated that high levels of total cholesterol or low-density lipoprotein (LDL)-cholesterol correlated with a decreased AD (52) and dementia risk (53).…”

Section: Epidemiological Studiesmentioning

confidence: 87%

Cholesterol and Alzheimer's disease: A still poorly understood correlation

et al. 2012

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SummaryA large amount of evidence suggests a pathogenic link between cholesterol homeostasis dysregulation and Alzheimer's disease (AD). In cell culture systems, the production of amyloidb (Ab) is modulated by cholesterol, and studies on animal models have consistently demonstrated that hypercholesterolemia is associated with an increased deposition of cerebral Ab peptides. Consequently, a number of epidemiological studies have examined the effects of cholesterol-lowering drugs (i.e., statins) in the prevention and the treatment of AD. However, while retrospective studies suggested a potential benefit of statin therapy, clinical trials produced inconsistent results. Here, we summarize the main findings from in vitro and in vivo research where the correlation between cholesterol and the neurodegenerative disorder was investigated. Recognition of this correlation could be an important step forward for our understanding of AD pathogenesis and, possibly, for the development of new therapeutic strategies.2012 IUBMB IUBMB Life, 64(12): 931-935, 2012

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“…Hypercholesterolemia in midlife is a risk factor for developing AD decades later (Kivipelto et al, 2002). Statins not only lower serum cholesterol levels, but also improve vasoreactivity in peripheral arteries and large cerebral arteries and are associated with a reduced prevalence of AD (Masse et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin Therapy is Associated with Greater and Faster Cerebral Hemodynamic Response

Fitzgerald

Wen

et al. 2008

Brain Imaging and Behavior

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Hypercholesterolemia in midlife increases the risk of subsequent cognitive decline, neurovascular disease, and Alzheimer's disease (AD), and statin use is associated with reduced prevalence of these outcomes. While statins improve vasoreactivity in peripheral arteries and large cerebral arteries, little is known about the effects of statins on cerebral hemodynamic responses and cognition in healthy asymptomatic adults. At the final visit of a 4-month randomized, controlled, double-blind study comparing atorvastatin 40 mg daily to placebo, 16 asymptomatic middle-aged adults (15 had useable data) underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) quantitative cerebral blood flow (qCBF), dynamic susceptibility contrast (DSC) and structural imagings of the brain. Using a memory recognition task requiring discrimination of previously viewed (PV) and novel (NV) human faces, fMRI was used to elicit activation from brain regions known to be vulnerable to changes associated with AD. The BOLD signal amplitude (PV > NV) and latency to each stimulus were tested on a voxel basis between the atorvastatin (n=8) and placebo (n=7) groups. Persons randomized to atorvastatin not only showed significantly greater BOLD amplitude in the right angular gyrus, left superior parietal lobule, right middle temporal and superior sulcus than the placebo group, but also decreased hemodynamic response latencies in the right middle frontal gyrus, left precentral gyrus, left cuneus and right posterior middle frontal gyrus. However, neither the resting cerebral blood flow (CBF) measured with ASL nor the mean transit time (MTT) of cerebral perfusion calculated from DSC showed differences in these regions in either group. The drug related BOLD differences during memory recognition suggest that atorvastatin may have improved cerebral small vessel vasoreactivity, possibly through an effect on endothelial function. Furthermore, these results suggest that the effect of atorvastatin on the task-induced BOLD signal may not be a simple consequence of baseline flow change.

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Apolipoprotein E ϵ4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease

Cited by 585 publications

References 28 publications

[P3–542]: Coronary Heart Disease and Risk for Cognitive Impairment or Dementia: A Systematic Review and Meta‐analysis

[P3–542]: Coronary Heart Disease and Risk for Cognitive Impairment or Dementia: A Systematic Review and Meta‐analysis

Cholesterol and Alzheimer's disease: A still poorly understood correlation

Atorvastatin Therapy is Associated with Greater and Faster Cerebral Hemodynamic Response

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