Excess Risk For Dementia Research Articles

Association of sleep duration with excess risk of dementia among shift workers in the UK biobank: a population-based cohort study.

Shift work was associated with elevated dementia risk. Definitive guidelines for sleep duration among shift workers have not been proposed. We aimed to identify sleep durations associated with elimination of excess dementia risk in shift workers. 285,213 dementia-free UK Biobank participants at baseline, aged 38-71years, were enrolled between 2006 and 2010 and followed up through 2022 in this cohort study. Cox proportional hazards models were used to examine the associations between shift work, sleep duration, and risk of dementia. The 285,213 participants included 49,079 shift workers and 236,134 non-shift workers. Over a median follow-up of 13.8years, 1887 dementia cases were documented. Current shift workers had significantly higher dementia risk than non-shift workers (hazard ratio [HR] 1.26; 95% CI 1.11-1.42). However, this excess risk was eliminated in shift workers with 8h of sleep (HR 1.02; 95% CI 0.80-1.29). Analysis of shift work frequency indicated that "sometimes" and "usually/always" shift work were associated with increased dementia risk compared to that of non-shift workers, but excess dementia risk was eliminated in members of either frequency group receiving 8h of sleep ("sometimes", HR 1.05; 95% CI 0.75-1.48; "usually/always", HR 0.98; 95% CI 0.70-1.35). Both "non-night shift" and "night shift" workers showed increased dementia risk compared to non-shift workers. Workers with 8h of sleep mitigated the excess risk (HR 1.13; 95% CI 0.84-1.53 and HR 0.86; 95% CI 0.59-1.26, respectively). 8-h sleep may eliminate excess dementia risk among shift workers, suggesting a potentially effective dementia prevention guideline for shift workers.

Association of Familial Hypercholesterolemia and Statin Use With Risk of Dementia in Norway

Hypercholesterolemia, which is a cardiovascular risk factor, may also be associated with dementia risk. The benefit of statin treatment on dementia risk is controversial. To determine whether individuals with familial hypercholesterolemia (FH), who have been exposed to lifelong hypercholesterolemia, have an excess risk of dementia and whether statin use is associated with dementia risk. This was a prospective cohort study performed from 2008 to 2018 in Norway. Statistical analysis was performed from January 2021 to February 2022. This study included individuals with genetically verified FH and age-matched and sex-matched controls obtained from the general Norwegian population. Dementia was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-03 and G30. Incident cases of total dementia, vascular dementia, Alzheimer disease-dementia in Alzheimer disease, and data on lipid-lowering medication were obtained from the Norwegian Patient Registry, Cause of Death Registry, and the Norwegian Prescription Database. Hazard ratios (HRs) for risk of dementia for individuals with FH vs matched controls were calculated using Cox regression. The cumulative sum of defined daily doses (DDDs) of statins prescribed during study follow-up was calculated for individuals with FH and was analyzed as a time-varying covariate with 3 levels: 1 to 4999 DDDs, 5000 to 10 000 DDDs, and more than 10 000 DDDs. Among the 3520 individuals with FH (1863 women [52.9%]; mean [SD] age at the start of follow-up, 51.8 [11.5] years) and the 69 713 controls (36 958 women [53.0%]; mean [SD] age at the start of follow-up, 51.7 [11.5] years), 62 patients with FH (39 women [62.9%]) and 1294 controls (801 women [61.9%]) had developed dementia over the course of 10 years of follow-up. Most dementia cases occurred among individuals aged 70 years and older (39 patients with FH [62.9%] and 870 patients [67.2%] in the control group). We found no excess risk of dementia in patients with FH vs matched controls (HR for total dementia, 0.9; 95% CI, 0.7-1.2). There was no association between cumulative DDDs of statins and total dementia in patients with FH with HRs of 1.2 (95% CI, 0.4-3.8) for cumulative DDDs of 5000 to 10 000 and 1.9 (95% CI, 0.7-5.0) for cumulative DDDs greater than 10 000. These findings suggest that individuals with FH have no excess risk of dementia compared with age-matched and sex-matched controls and that there is no association between use of statins and risk of dementia in patients with FH.

Association of Subjective Cognitive Decline with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Longitudinal Studies.

Subjective cognitive decline (SCD) as an early pathological manifestation of brain aging has become more prevalent among older adults. We aimed to investigate the associations of subjective cognitive decline (SCD) with the combined risk of cognitive impairment and dementia. We performed a systematic review and meta-analysis via searching Embase, PubMed and Cochrane electronic databases from January 1 st 1970 to June 4th, 2020. Prospective cohort studies Participants: Healthy individuals were recruited from community, clinics and population. Healthy individuals with SCD were classified into exposure groups, while those without were considered as the reference group. Adjusted relative risks (RR) were estimated in a random-effects model. Both primary and subgroup analyses were conducted. Of 28,895 identified studies, 21 studies containing 22 cohorts were eligible for inclusion in the meta-analysis. SCD increased the risk of subsequent cognitive disorders (RR=2.12, 95% confidence intervals [CI] =1.75-2.58, I2=87%, P<0.01). To be specific, SCD conferred a 2.29-fold excess risk for cognitive impairment (RR=2.29, 95% CI=1.66-3.17, I2=83%, P<0.01) and a 2.16-fold excess risk for dementia (RR=2.16, 95% CI=1.63-2.86, I2=81%, P<0.01). In subgroup analyses, participants with SCD in the subgroup of 65-75 years old, long-education (>15 years) subgroup and subgroup of clinics showed a higher risk of developing objective cognitive disorders. SCD is associated with an increased combined risk of cognitive impairment and incident dementia and should be considered a risk factor for objective cognitive disorders.

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

Abstract Background Previous studies investigating the association between coronary artery bypass grafting (CABG) and risk for dementia show conflicting results. Purpose To compare the long-term risk for dementia in CABG patients to matched individuals in the general population, and to identify independent predictors for developing dementia after CABG. Methods Data from the SWEDEHEART registry and three other mandatory national registries were merged to compare all patients who underwent isolated CABG in Sweden from 1992 to 2015 (n=111.335) with an age- and sex-matched control individuals from the general population (n=222.396). Cumulative incidence adjusted for the competing risk for death and Cox regression models with Hazard Ratio (HR) and 95% confidence interval (CI) adjusted for age, gender, co-morbidity and socioeconomic variables, were used to calculate the risk of dementia. Median follow-up was 10.1 years (IQR 2.5–14.7) among CABG patients and 10.7 years (5.6–15.7) among the controls. Identified interactions of the excess risk for dementia with sex and age categories (&amp;lt;65, 65-&amp;lt;75, ≥75 years) resulted in analyses being stratified on those sub-cohorts. Results The overall cumulative incidence at 20 years follow up of all-cause dementia was 9.6% (95% CI 9.4–9.9) among CABG patients and 9.0 (8.8–9.2) among individuals in the general population. The adjusted relative risk for all-cause dementia was increased among CABG patients &amp;lt;65 years and 65–75 years, (HR 1.29 (95% CI 1.17–1.41) and HR 1.06 (1.01–1.11), respectively (fig 1). The risk for all-cause dementia was higher in CABG women than in CABG men (HR 1.62 (1.30–2.03) vs HR 1.22 (1.10–1.35)). In the oldest age group (75 years and older) the risk for all cause dementia, vascular dementia and Alzheimer's disease was lower for CABG patients compared to controls (HR 0.73 (0.69–0.78). Female CABG patients &amp;lt;65 years had an increased risk for Alzheimer's disease (HR 1.83 (1.06–3.15). Hypertension, diabetes, preoperative stroke, renal failure, heart failure, atrial fibrillation, depression and low income were independent predictors for all-cause dementia in CABG patients. Conclusion CABG patients younger than 75 years at the time of surgery have an increased risk of all-cause dementia compared to an age- and sex-matched population. Women younger than 65 years that underwent CABG had also a markedly higher risk for Alzheimer disease. Increased awareness of the higher risk for dementia in younger CABG patients is warranted to avoid delay of diagnosis and treatment. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Swedish Heart and Lung Foundation, Swedish State

Low fasting values of serum insulin in a cohort of nondiabetic women followed over 34 years: Evidence for an alternative pathway to dementia

Background A previous study reported a U-shaped association between fasting insulin and dementia in a 5-year follow-up of a male cohort [1] . More recently, a cross-sectional study of 262 older adults free of diabetes and cognitively normal showed that decreased blood insulin below optimal levels was associated with higher beta amyloid deposition and neurodegeneration [2] . The purpose of the present study was to investigate the prospective association between fasting serum insulin and dementia in a representative population of women followed over 34 years, taking into account the incidence of diabetes. Methods Fasting values for insulin and glucose were obtained from serum samples in 1212 nondiabetic women aged 38–60 at the 1968 baseline. Risk of dementia was assessed by Cox proportional hazard regression adjusting for insulin, glucose, and other covariates, and, in a second model, after censoring for incident cases of diabetes. Incident diabetes was considered as a third endpoint, for comparison with dementia. Results Over 34 years, we observed 142 incident cases of dementia. The lowest tertile of insulin was associated with excess risk for dementia, hazard ratio (HR) = 2.33, 95% confidence interval = (1.52, 3.58), compared to the intermediate tertile, but the highest tertile of insulin was not, HR = 1.27 (0.81, 2.02). These associations were also seen for dementia without diabetes comorbidity. In contrast, high but not low insulin predicted incident diabetes (115 cases), HR = 1.69 (1.08, 2.66) and HR = 0.76 (0.43, 1.36), respectively. Conclusion This study provides epidemiological evidence for a new pathway to dementia that is characterized by low fasting serum insulin and differs from the metabolic pathway via hyperinsulinemia or diabetes. The identification of the tails of the U-shaped risk curve for insulin and dementia with distinct pathways was possible due to the long follow-up, and by comparing the associations of insulin with different dementia endpoints and diabetes. The distinction between alternative pathways will explain inconsistent epidemiological findings regarding risk factors of dementia and its subtypes.

Does Obesity Increase the Risk of Dementia: A Literature Review.

Obesity and dementia are both associated with an increased risk of Alzheimer's disease (AD), and underlying neurodegenerative changes. Review articles provide evidential support that obesity and dementia result in an early old-age memory crisis. Obesity triggering vascular dementia decreases not only blood supply to the brain, but also increases fat cells that damage the brain white matter leading to loss of cognitive and intellectual behaviour. Adipocyte-secreted proteins and inflammatory cytokines explain the association between obesity and increased risk of dementia. Late-life elevated body mass index (BMI) confers a lower risk of having dementia. The hormone leptin explained the mechanism for the reverse association. Future studies need to reveal the linkage between adiposity and excess risk of dementia and AD.

Spouse with schizophrenia and risk of dementia.

Increased prevalence of lifestyle risk factors or shared etiology may underlie the association between schizophrenia and the subsequent risk of dementia. We explored the association between having a spouse with schizophrenia and the risk of dementia. We found a positive relationship between having a spouse with schizophrenia and vascular dementia in individuals without a mental disorder themselves but no association between having a spouse with schizophrenia and Alzheimer's dementia. As spouses share environmental risk factors and lifestyle, this might suggest that the excess risk of dementia in probands with schizophrenia could be ascribed to the unhealthy living environment among individuals with schizophrenia.

Does Schizophrenia in Offspring Increase the Risk of Developing Alzheimer's Dementia

Background/Aims: Prior studies have consistently found a higher risk of dementia in individuals with schizophrenia, but whether this is due to a common etiology between the disorders remains obscure. We wanted to elucidate this association by investigating whether schizophrenia in offspring increases the risk of Alzheimer's dementia. Methods: All individuals born between 1930 and 1953 were identified through national registers and followed from their 50th birthday until the date of Alzheimer's dementia, death or end of the study. Regressions were performed to evaluate the association between offspring with schizophrenia and Alzheimer's dementia. Results: Individuals with offspring with schizophrenia did not have an increased risk of Alzheimer's dementia [incidence rate ratio (IRR), 0.97; 95% CI, 0.88-1.07] compared to individuals with offspring without psychiatric contact. This finding remained stable when evaluating early-onset (IRR, 1.10; 95% CI, 0.91-1.31) and late-onset Alzheimer's dementia (IRR, 0.92; 95% CI, 0.88-1.07). Similar findings were made for vascular and unspecified dementia. Conclusion: The finding of no familial coaggregation between schizophrenia and Alzheimer's dementia may suggest that no common etiology between the disorders exists. This may indicate that the excess risk of dementia in individuals with schizophrenia is a by-product of the higher rates of somatic comorbidity and adverse health risk factors among these individuals.

Stroke Findings in the Women's Health Initiative

The Women's Health Initiative (WHI) clinical trials of estrogen with or without progestin versus placebo in 27,341 postmenopausal women are the largest randomized, placebo-controlled, double-blind clinical trials to look at the effect of hormone therapy on the outcomes of stroke, dementia, and cognition. Data from a parallel prospective observational study of 93,676 women examine biomarkers and risk factors associated with stroke. We summarize the results of 29 published articles in the WHI with stroke or cognition as outcomes of interest. Estrogen alone or in combination with progestin resulted in approximately 50% excess risk of ischemic stroke and in a 76% excess risk of dementia in women 65 years or older. Other risk factors for stroke identified in the WHI were panic attacks, depression, use of antidepressants (particularly selective serotonin reuptake inhibitors for hemorrhagic but not ischemic stroke), high triglycerides, low walking speed, long sleep duration, certain inflammatory factors, and systolic blood pressure variability. Hormone therapy has adverse effects on the brain as manifested by higher risks of stroke and dementia. Additional risk factors for stroke identified in WHI should be followed up to determine if reversing them would result in lower stroke rates.

Association between APOE genotype, neuropathology and dementia in the older population of England and Wales

Apolipoprotein E (APOE) genotype is the major genetic risk factor for sporadic Alzheimer's disease (AD) but it is unclear how this is mediated. Most studies of APOE genotype have used case-control design to compare groups differing by two variables: i.e. dementia and AD pathology, so it is unclear to which of these variables APOE genotype is more strongly related. The prospective Medical Research Council Cognitive Function and Ageing Study neuropathology cohort is population-based sample in which donations are unbiased by dementia status. We investigated the association between APOE genotypes and neuropathological and cognitive data in this cohort (n = 310). APOEε4 was associated with an increased risk of diffuse plaques, neuritic plaques, tangles and cerebral amyloid angiopathy. APOEε4 was not associated with infarcts, lacunes, haemorrhages or small vessel disease. APOEε2 appeared to have a protective effect on AD pathology and also on the risk of cortical atrophy. APOE genotype had a non-significant effect on the presence of dementia after adjusting for AD pathology. APOE genotype is associated with each of the key features of AD pathology but not with cerebrovascular disease other than cerebral amyloid angiopathy. The excess risk of dementia in those with an APOEε4 allele is explained by the pathological features of AD. However, it remains unclear to what extent cognitive dysfunction is caused by these specific pathological features or more directly by closely related APOE-associated mechanisms.

Epidemiological Studies of the Effect of Stroke on Incident Dementia

Stroke is implicated in the incidence of dementia, and the risk of poststroke dementia is well characterized, but the excess risk of dementia in those with stroke compared with those without stroke is not well known. We conducted a systematic review of the excess risk of incident dementia conferred by stroke. Studies of the risk of incident dementia in the population with stroke compared with the population without stroke were identified and compared. Sixteen studies were identified with all but one conducted in a community setting. A history of stroke doubles the risk of incident dementia in the older population. This increase is not explained by demographic or cardiovascular risk factors or by prestroke cognitive decline. The excess risk of incident dementia diminishes with time after stroke and may be higher in those without an APOE epsilon4 allele. There is no excess risk of incident dementia in those aged >85 years with a history of stroke compared to those aged >85 years without stroke. The effect of stroke on dementia incidence in the population is not explained by common risk factors. At this time of population aging and increased stroke survival, more research is needed to determine to what extent efforts to reduce the incidence of stroke will affect the incidence of dementia.

How Does HT Affect the Brains of Older Menopausal Women

Hormone therapy is associated with excess risk for dementia in older women (age, ≥65). In the Women’s Health Initiative Memory Study (WHIMS; a WHI