High cholesterol levels in late life assotiated with a reduced risk of dementia
ABSTRACT To examine the longitudinal association between plasma total cholesterol and triglyceride levels and incident dementia.
Neuropsychiatric, anthropometric, laboratory, and other assessments were conducted for 392 participants of a 1901 to 1902 birth cohort first examined at age 70. Follow-up examinations were at ages 75, 79, 81, 83, 85, and 88. Information on those lost to follow-up was collected from case records, hospital linkage system, and death certificates. Cox proportional hazards regression examined lipid levels at ages 70, 75, and 79 and incident dementia between ages 70 and 88.
Increasing cholesterol levels (per mmol/L) at ages 70 (hazard ratio [HR] 0.77, 95% CI: 0.61 to 0.96, p = 0.02), 75 (HR 0.70, CI: 0.52 to 0.93, p = 0.01), and 79 (HR 0.73, CI: 0.55 to 0.98, p = 0.04) were associated with a reduced risk of dementia between ages 79 and 88. Examination of cholesterol levels in quartiles showed that the risk reduction was apparent only among the highest quartile at ages 70 (8.03 to 11.44 mmol/L [311 to 442 mg/dL]; HR 0.31, CI: 0.11 to 0.85, p = 0.03), 75 (7.03 to 9.29 mmol/L [272 to 359 mg/dL]; HR 0.20, CI: 0.05 to 0.75, p = 0.02), and 79 (6.82 to 9.10 mmol/L [264 to 352 mg/dL]; HR 0.45, CI: 0.17 to 1.23, p = 0.12). Triglyceride levels were not associated with dementia.
High cholesterol in late life was associated with decreased dementia risk, which is in contrast to previous studies suggesting high cholesterol in mid-life is a risk factor for later dementia. The conflicting results may be explained by the timing of the cholesterol measurements in relationship to age and the clinical onset of dementia.
Full-textDOI: · Available from: Bertil Steen, Aug 22, 2015
- SourceAvailable from: Atanu Biswas
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- "Many case -control studies have also confirmed that mild hypercholesterolemia accompanies late-onset AD   . 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   . The statin group of cholesterol lowering agents has been shown to produce beneficial effects in AD subjects in some studies . "
ABSTRACT: 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, pro-inflammatory 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.08/2015; 6(4):282-99. DOI:10.14336/AD.2014.002
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- "Based on previous findings which suggest significant associations between lipoproteins and cognitive performance (Elias et al., 2005; Mielke et al., 2005; Schreurs, 2010), we expected that higher levels of TC, LDL-C, and HDL-C and lower levels of TG would be associated with better cognitive performance. "
ABSTRACT: Research shows that lipid levels may be associated with cognitive function, particularly among women. We aimed to examine total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein (HDL), and HDL/LDL ratio in relation to cognitive performance, measured with six well-established cognitive domains and a composite cognitive score (CCS). In this cross-sectional study, biomarkers and neuropsychological assessment were available for 141 adults with MMSE scores ≥ 24 (mean age = 69 years, 47% female, mean education = 14.4 years) attending a neuropsychological evaluation. Ordinary least squares regressions were adjusted for age, gender, education, and depressive symptoms in Model 1 and also for apolipoprotein E4 (APOE4) status in Model 2. High-density lipoprotein cholesterol (HDL-C) was associated with better CCS (β = 0.24; p = 0.014). This association was significant among women (β = 0.30; p = 0.026) and not among men (β = 0.20; p = 0.124). HDL-C was also related to attention/working memory (β = 0.24; p = 0.021), again only among women (β = 0.37; p = 0.012) and not men (β = 0.15; p = 0.271). Adjusting for APOE4 yielded significance for high HDL-C and CCS (β = 0.24; p = 0.022). HDL-C was the main lipoprotein affecting cognitive function, with results somewhat more pronounced among women. Research should investigate the possibility of finding ways to boost HDL-C levels to potentially promote cognitive function.International Psychogeriatrics 03/2015; DOI:10.1017/S1041610215000320 · 1.89 Impact Factor
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- "Interestingly , 8-month old A␤PP Swe /PS1E9 mice on a pure C57BL/6J background did not demonstrate significantly different levels of cholesterol, while 15-month old transgenic mice had significantly lower cholesterol levels compared to control mice . It is noteworthy that decreased levels of cholesterol in cerebral spinal fluid and plasma have been found in patients with AD  . "
ABSTRACT: Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer's disease (AD). Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo. Here we evaluate the preventative properties of long-term CBD treatment in male AβPPSwe/PS1ΔE9 (AβPP × PS1) mice, a transgenic model of AD. Control and AD transgenic mice were treated orally from 2.5 months of age with CBD (20 mg/kg) daily for 8 months. Mice were then assessed in the social preference test, elevated plus maze, and fear conditioning paradigms, before cortical and hippocampal tissues were analyzed for amyloid load, oxidative damage, cholesterol, phytosterols, and inflammation. We found that AβPP × PS1 mice developed a social recognition deficit, which was prevented by CBD treatment. CBD had no impact on anxiety or associative learning. The prevention of the social recognition deficit was not associated with any changes in amyloid load or oxidative damage. However, the study revealed a subtle impact of CBD on neuroinflammation, cholesterol, and dietary phytosterol retention, which deserves further investigation. This study is the first to demonstrate CBD's ability to prevent the development of a social recognition deficit in AD transgenic mice. Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.Journal of Alzheimer's disease: JAD 07/2014; 42(4). DOI:10.3233/JAD-140921 · 4.15 Impact Factor