Cardiovascular disease and Alzheimer's disease: common links

This study examined the relationship between sleep disorders and the risk of dementia in patients with newly diagnosed type 2 diabetes. This study used the Korean Health Screening Cohort data and included 39 135 subjects aged ≥40 years with new-onset type 2 diabetes between 2004 and 2007, with follow-up throughout 2013. Sleep disorders were measured by F51(sleep disorders not due to a substance or known physiological condition) or G47(sleep disorders) under International Classification of Diseases, Tenth Revision (ICD-10) codes as a primary diagnosis, and the adjusted hazard ratio (AHR) and 95% CI of all-cause dementia, Alzheimer disease, vascular dementia, and other dementia were estimated using multivariable Cox proportional hazards regression models. In the patients with type 2 diabetes with an age range between 42 and 84 years (M = 57.8, SD = 9.5), this study identified 2059 events of dementia during an average follow-up time of 5.7 years. In patients with type 2 diabetes, subjects with sleep disorders were associated with an increased risk of all-cause dementia (AHR, 1.46; 95% CI, 1.19-1.80), Alzheimer disease (AHR, 1.39; 95% CI, 1.02-1.88), and other dementia (AHR, 1.69; 95% CI, 1.23-2.31) compared to those without sleep disorders. Men (AHR, 1.93; 95% CI, 1.42-2.62) and older adults (AHR, 1.70; 95% CI, 1.35-2.15) with sleep disorders were associated with an increased risk of dementia than their counterparts without sleep disorders among patients with type 2 diabetes. These findings suggest that sleep disorders are significantly associated with an increased risk of dementia in patients with new-onset type 2 diabetes.

Prevention of psychiatric illness in the elderly, I: Path to prevention of dementia

The Risk of New Onset Dementia and/or Alzheimer Disease among Patients with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

To examine the association of serum total cholesterol (TC) and high density lipoprotein (HDL) levels and subsequent incidence of dementia and Alzheimer disease (AD) in a population-based cohort study. A cohort of cognitively intact persons, aged 65 and older, was randomly selected from Group Health Cooperative (GHC), a large health maintenance organization, and was assessed biennially for dementia. Premorbid levels of TC and HDL were obtained from a computerized clinical laboratory database at GHC. Cox proportional hazards regression was used to calculate hazard ratios (HR, 95% CI) for dementia and AD associated with quartiles of TC and HDL levels. Of the 2,356 eligible participants, 2,141 had at least one serum TC measure prior to the initial enrollment. Using the lowest TC quartiles as the reference group, the HR in the highest TC quartiles was not significantly elevated for dementia (1.16, 0.81 to 1.67) or for AD (1.00, 0.61 to 1.62) after adjusting for age, sex, education, baseline cognition, vascular comorbidities, body mass index, and lipid-lowering agent use. Serum HDL showed a similar lack of significant association with risk of dementia or AD. Models that included the presence of one or more APOE-epsilon4 alleles showed a typical association of epsilon4 with AD risk. This association was not materially modified by inclusion of TC level. The data do not support an association between serum total cholesterol or high density lipoprotein in late life and subsequent risk of dementia or Alzheimer disease (AD). The increased risk of AD with APOE-epsilon4 is probably not mediated by serum total cholesterol levels.

Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimer's disease (AD). The researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I (2) statistic. Seven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I (2) = 0%-40%, p ≥ .16). An increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.

Is risk of Alzheimer disease a reason to use dietary supplements?

Younger patients have an increased risk for dementia after coronary artery bypass grafting, a population-based cohort study from the SWEDEHEART registry

Circulation: Clinical Summaries.

Introduction: Although total cholesterol (TC) variability is suggested as a risk factor for cardiovascular and cerebrovascular disease, there is no previous study to evaluate the association between TC variability and the development of dementia.Methods: Using the Korean National Health Insurance Service–Health Screening Cohort (NHIS-HEALS), the main outcomes were newly diagnosed all-cause dementia, Alzheimer's disease (AD), or vascular dementia (VaD) between January 1, 2008, and December 31, 2015. Visit-to-visit TC variability was measured as variability independent of the mean (TC-VIM), coefficient variance (TC-CV), and standard deviation (TC-SD).Results: In a total of 131,965 Koreans, there were 3,722 all-cause dementia (2.82%), 2,776 AD (2.10%), and 488 VaD (0.37%) during the median follow-up of 8.4 years. Kaplan–Meier curves showed increased cumulative incidences for all in the group of the highest quartiles of TC variability compared to the others. Regression using the Fine and Gray hazards model showed a steadily increasing risk of all-cause dementia with higher quartiles of TC variability. After adjusting for confounders including mean TC level and comparing the highest and lowest TC-VIM quartiles, the hazard ratios (HRs) for all-cause dementia and AD were 1.15 [95% confidence interval (CI) = 1.05–1.27; P = 0.003] and 1.12 (95% CI = 1.00–1.25; P = 0.040), respectively. The incidence of VaD was not significantly higher in the higher-quartile groups compared to that in the lowest-quartile group in TC-VIM variability (HR 1.22; 95% CI = 0.95–1.59; P = 0.122). These associations were consistent with TC variability defined by TC-CV or TC-SD.Conclusions: For the first time, we have demonstrated that a higher visit-to-visit variability in TC independent of mean TC is associated with an increased risk of all-cause dementia and AD in the general population.

Association of dietary cholesterol and egg intakes with the risk of incident dementia or Alzheimer disease: the Kuopio Ischaemic Heart Disease Risk Factor Study ,

BackgroundSeveral epidemiological studies have suggested that vitamin D status is associated with risk of dementia in general populations. However, due to the synergistic effect between diabetic pathology and neuroinflammation, and the prothrombotic profile in patients with diabetes, whether vitamin D is associated with risk of dementia among patients with diabetes is unclear. This study aimed to investigate the associations of circulating vitamin D levels with risks of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD) among adults with type 2 diabetes (T2D).Methods and findingsThis study included 13,486 individuals (≥60 years) with T2D and free of dementia at recruitment (2006–2010) from the UK Biobank study. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using the chemiluminescent immunoassay method at recruitment. Serum 25(OH)D ≥ 75 nmol/L was considered sufficient, according to the Endocrine Society Clinical Practice Guidelines. Incidence of all-cause dementia, AD, and VD cases was ascertained using electronic health records (EHRs). Each participant’s person-years at risk were calculated from the date of recruitment to the date that dementia was reported, date of death, date of loss to follow-up, or 28 February 2018, whichever occurred first. Among the 13,486 individuals with T2D (mean age, 64.6 years; men, 64.3%), 38.3% had vitamin D ≥ 50 nmol/L and only 9.1% had vitamin D ≥ 75 nmol/L. During a mean follow-up of 8.5 years, we observed 283 cases of all-cause dementia, including 101 AD and 97 VD cases. Restricted cubic spline analysis demonstrated a nonlinear relationship between serum 25(OH)D and risk of all-cause dementia (Pnonlinearity < 0.001) and VD (Pnonlinearity = 0.007), and the nonlinear association reached borderline significance for AD (Pnonlinearity = 0.06), with a threshold at around a serum 25(OH)D value of 50 nmol/L for all the outcomes. Higher serum levels of 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD. The multivariate hazard ratios and 95% confidence intervals for participants who had serum 25(OH)D ≥ 50 nmol/L, compared with those who were severely deficient (25[OH]D < 25 nmol/L), were 0.41 (0.29–0.60) for all-cause dementia (Ptrend < 0.001), 0.50 (0.27–0.92) for AD (Ptrend = 0.06), and 0.41 (0.22–0.77) for VD (Ptrend = 0.01). The main limitation of the current analysis was the potential underreporting of dementia cases, as the cases were identified via EHRs.ConclusionsIn this study, we observed that higher concentrations of serum 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD among individuals with T2D. Our findings, if confirmed by replication, may have relevance for dementia prevention strategies that target improving or maintaining serum vitamin D concentrations among patients with T2D.

Advances in Vascular Cognitive Impairment

Cognitive decline may lead to dementia whose most frequent cause is Alzheimer's disease (AD). Among the many potential risk factors of cognitive decline and AD, diet raises increasing interest. Most studies considered diet in the frame of a single nutrient approach with inconsistent results. A novel approach to examine the link between nutrition and cognitive function is the use of dietary patterns. The aim of the present review was to update and complete the body of knowledge about dietary patterns in relationship with various cognitive outcomes in the elderly. Two approaches can be used: a priori and a posteriori patterns. A priori patterns are defined by the adhesion to a pre-defined healthy diet using a score such as the Mediterranean diet (MeDi) score, the Healthy Eating Index, the Canadian Healthy Eating Index, the French National Nutrition and Health Programme (Programme National Nutrition Santé) Guideline Score (PNNS-GS), the Recommended Food Score (RFS) and Dietary Approaches to Stop Hypertension (DASH). MeDi score, RFS, PNNS-GS and DASH have been associated with lower risks of cognitive impairment, cognitive decline, and dementia or AD. Principal components analysis, reduced rank regression and clustering methods allow the identification of 'healthy' patterns associated with lower risk of cognitive decline. However, some studies did not report any associations with cognitive outcomes and results are discordant especially regarding MeDi and the risk of dementia. Several methodological challenges should be overcome to provide a higher level of evidence supporting the development of nutritional policies to prevent cognitive decline and AD.

Introduction: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. Method: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. Results: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. Conclusion: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia.

There is increasing evidence that establishes a connection between fluctuations in glucose metabolism and the onset of Alzheimer's disease (AD). Current research supports the notion that this metabolic imbalance significantly affects cognitive health. However, the specific mechanisms through which these fluctuations influence neurodegeneration, eventually leading to AD, require further exploration. This study aims to determine the risk of AD among individuals with fluctuations in blood glucose levels,with or without type 2 diabetes mellitus (T2DM), further providing the most recent and thorough overview of the evidence in this area. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a thorough search was carried out utilizing particular phrases in the PubMed, Elsevier, Research Gate, and Cochrane databases: ("glucose variability" or "glycemic variability" or "glucose fluctuation" or "glucose instability" or "glycemic fluctuation") and ("Alzheimer's disease" or "Alzheimer disease" or "Alzheimer dementia" or "Alzheimer"). Studies published between January 2014 to January 2024, written in English, and examining the relationship between glucose variability and AD, were included. The outcomes measured were risk of cognitive impairment and AD, cognitive performance, and risk of AD. The results of the literature search produced 142 records, with six studies meeting the eligibility criteria. Parameters for glycemic variability included fasting plasma glucose (FPG) variability, glycated hemoglobin (HbA1c) variability, FPG variability independent of the mean (VIM), FPG coefficient of variation (CV), and FPG standard deviation (SD). The studies revealed a positive correlation between glycemic variability and the risk of AD over time, and the findings indicated that maintaining stable glycemic levels may reduce the risk of cognitive decline among individuals with or without T2DM. Due to the small number of studies that are currently available, despite a calculated relative risk of 2.65 indicating a higher risk of AD among subjects with glycemic variability, the inclusion of the null value in the confidence interval (0.61-11.45) renders these findings not statistically significant. This comprehensive review demonstrated that, in people with or without diabetes, glycemic variability influences cognitive decline and the risk of AD. The studies demonstrated a correlation between higher fluctuations in glucose levels and an increased risk of AD, highlighting the importance of managing blood sugar levels to mitigate dementia risks. Despite these strong associations, the actual incidence rates of AD in the studied populations remained relatively low. Overall, the results were not statistically significant. Further research is recommended to explore the risk of AD among individuals with fluctuations in blood glucose levels.