Cholesterol as a Risk Factor for Dementia and Cognitive Decline: A Systematic Review of Prospective Studies With Meta-Analysis
The relationships between total serum cholesterol (TC) and dementia and between TC and cognitive decline were investigated in a systematic review of 18 prospective studies. Follow-ups ranged from 3 to 29 years, and included a total of 14,331 participants evaluated for Alzheimer disease (AD), 9,458 participants evaluated for Vascular dementia (VaD), 1,893 participants evaluated for cognitive decline, and 4,793 participants evaluated for cognitive impairment. Compatible results were pooled using meta-analysis. Consistent associations between high midlife TC and increased risk of AD, and high midlife TC and increased risk of any dementia were found. There was no evidence supporting an association between late-life TC and AD, or between late-life TC and any dementia. No study reported a significant association between TC (measured in midlife or late-life) and VaD. An association between high midlife TC and cognitive impairment was found but there was only weak evidence for an association between TC and cognitive decline. Two of seven studies reporting data on the interaction between TC and apolipoprotein e4-allele had significant effects. Results suggest the effect of TC on dementia risk occurs in midlife but not late-life, and that there may be different cardiovascular risk factor profiles for AD and VaD. Results from additional studies involving long-term follow-up of midlife samples will allow for clarification of the association between age, TC and risk of specific types of dementia. These data are required to inform recommendations of modulation of cholesterol to reduce or delay dementia risk.
Available from: Kate Walters
- "Aspirin use may be a marker for underlying vascular risk. The directions of associations of some factors, such as weight and cholesterol, have been shown to change in later life with the onset of disability, frailty and cognitive decline and potential pre-clinical dementia[38,39]. In our study, the 'high risk' population may include those with pre-clinical or undetected/recorded dementia, which may explain some of the associations observed with individual factors. "
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ABSTRACT: Background: Existing dementia risk scores require collection of additional data from patients, limiting their use in practice. Routinely collected healthcare data have the potential to assess dementia risk without the need to collect further information. Our objective was to develop and validate a 5-year dementia risk score derived from primary healthcare data.
Methods: We used data from general practices in The Health Improvement Network (THIN) database from across the UK, randomly selecting 377 practices for a development cohort and identifying 930,395 patients aged 60–95 years without a recording of dementia, cognitive impairment or memory symptoms at baseline. We developed risk algorithm models for two age groups (60–79 and 80–95 years). An external validation was conducted by validating the model on a separate cohort of 264,224 patients from 95 randomly chosen THIN practices that did not contribute to the development cohort. Our main outcome was 5-year risk of first recorded dementia diagnosis. Potential predictors included sociodemographic, cardiovascular, lifestyle and mental health variables.
Results: Dementia incidence was 1.88 (95 % CI, 1.83–1.93) and 16.53 (95 % CI, 16.15–16.92) per 1000 PYAR for those aged 60–79 (n = 6017) and 80–95 years (n = 7104), respectively. Predictors for those aged 60–79 included age, sex, social deprivation, smoking, BMI, heavy alcohol use, anti-hypertensive drugs, diabetes, stroke/TIA, atrial fibrillation, aspirin, depression. The discrimination and calibration of the risk algorithm were good for the 60–79 years model; D statistic 2.03 (95 % CI, 1.95–2.11), C index 0.84 (95 % CI, 0.81–0.87), and calibration slope 0.98 (95 % CI, 0.93–1.02). The algorithm had a high negative predictive value, but lower positive predictive value at most risk thresholds. Discrimination and calibration were poor for the 80–95 years model.
Conclusions: Routinely collected data predicts 5-year risk of recorded diagnosis of dementia for those aged 60–79, but not those aged 80+. This algorithm can identify higher risk populations for dementia in primary care. The risk score has a high negative predictive value and may be most helpful in ‘ruling out’ those at very low risk from further testing or intensive preventative activities.
Keywords: Dementia, Primary care, Risk assessment, Routinely collected data
Available from: Jason Brandt
- "Kivipelto et al.  found that obesity was a significant risk factor for dementia over a 20 year follow-up period, whereas Barnes et al.  found that low body mass index (BMI) was a risk factor for the development of dementia over 6 years. As pointed out by Anstey et al.  , high cholesterol and high BMI in mid-life are both significant risk factors for AD, but neither is a risk factor when it appears in late-life. Thus, the time frame over which the risk factor is assessed may be an important factor. "
Available from: Janie Corley
- "First published online 15 July 2014. et al., 2005; Solomon et al., 2007; Anstey et al., 2008; Beydoun et al., 2010; Reynolds et al., 2010). An increased risk of cardiovascular pathologies with a higher midlife TC (Simons et al., 2001; Berry et al., 2008) may, in part, explain the later risk of cognitive impairment. "
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We examined the associations between serum cholesterol measures, statin use, and cognitive function measured in childhood and in old age. The possibility that lifelong (trait) cognitive ability accounts for any cross-sectional associations between cholesterol and cognitive performance in older age, seen in observational studies, has not been tested to date.
Participants were 1,043 men and women from the Lothian Birth Cohort 1936 Study, most of whom had participated in a nationwide IQ-type test in childhood (Scottish Mental Survey of 1947), and were followed up at about age 70 years. Serum cholesterol measures included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and cholesterol:HDL cholesterol ratio. Cognitive outcome measures were age 70 IQ (using the same test as at age 11 years), general cognitive ability (g), processing speed, memory, and verbal ability.
Higher TC, higher HDL-C, and lower triglycerides were associated with higher age 70 cognitive scores in most cognitive domains. These relationships were no longer significant after covarying for childhood IQ, with the exception a markedly attenuated association between TC and processing speed, and triglycerides and age 70 IQ. In the fully adjusted model, all conventionally significant (p < 0.05) effects were removed. Childhood IQ predicted statin use in old age. Statin users had lower g, processing speed, and verbal ability scores at age 70 years after covarying for childhood IQ, but significance was lost after adjusting for TC levels.
These results suggest that serum cholesterol and cognitive function are associated in older age via the lifelong stable trait of intelligence. Potential mechanisms, including lifestyle factors, are discussed.
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