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Background: Although many studies have investigated the association between stress and risk of dementia, findings are inconsistent due to the variation in the measures used to assess stress.Objective: We conducted a systematic review and meta-analysis to investigate the association between psychological stress (including neuroticism, stressful life events, and perceived stress) and the risk of incident dementia and mild cognitive impairment in adults.Methods: PsycINFO, Embase, and MEDLINE were searched to October 2020 for eligible observational, prospective studies. Of the 1,607 studies screened, 26 (24 unique cohorts) were included in the qualitative analysis and 16 (15 unique cohorts) were included in the quantitative analysis.Results: Across studies, higher perceived stress was significantly associated with an increased risk of mild cognitive impairment (Cases/Total N = 207/860: hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.03-1.38) and all-cause dementia (Cases/Total N = 203/1,882: HR = 1.44, 95% CI = 1.07-1.95). Exposure to two or more stressful life events (versus none) was significantly associated with an increased risk of all-cause dementia (Cases/Total N = 3,354/11,597: HR = 1.72, 95% CI = 1.14-2.60), while one or more stressful life events was not. Higher neuroticism was significantly associated with an increased risk of Alzheimer's disease dementia (Cases/Total N = 497/4,771: HR = 1.07, 95% CI = 1.01-1.12), but not all-cause dementia.Conclusion: This review suggests that psychological stress in adulthood is associated with an increased risk of dementia. Further research is needed to clarify the mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Background: An association between chronic infectious diseases and development of dementia has been suspected for decades, based on the finding of pathogens in postmortem brain tissue and on serological evidence. However, questions remain regarding confounders, reverse causality, and how accurate, reproducible and generalizable those findings are.Objective: Investigate whether exposure to Herpes simplex (manifested as herpes labialis), Chlamydophila pneumoniae (C. pneumoniae), Helicobacter pylori (H. pylori), and cytomegalovirus (CMV) modifies the risk of dementia in a populational cohort.Methods: Questionnaires regarding incidence of herpes infections were administered to Original Framingham Study participants (n = 2,632). Serologies for C. pneumoniae, H. pylori, and CMV were obtained in Original (n = 2,351) and Offspring cohort (n = 3,687) participants. Participants are under continuous dementia surveillance. Brain MRI and neuropsychological batteries were administered to Offspring participants from 1999-2005. The association between each infection and incident dementia was tested with Cox models. Linear models were used to investigate associations between MRI or neuropsychological parameters and serologies.Results: There was no association between infection serologies and dementia incidence, total brain volume, and white matter hyperintensities. Herpes labialis was associated with reduced 10-year dementia risk (HR 0.66, CI 0.46-0.97), but not for the duration of follow-up. H. pylori antibodies were associated with worse global cognition (β -0.14, CI -0.22, -0.05).Conclusion: We found no association between measures of chronic infection and incident dementia, except for a reduction in 10-year dementia risk for patients with herpes labialis. This unexpected result requires confirmation and further characterization, concerning antiviral treatment effects and capture of episodes. [ABSTRACT FROM AUTHOR]

Background: African Americans (AA) have a higher Alzheimer's disease (AD) prevalence and report more perceived stress than White Americans. The biological basis of the stress-AD link is unclear. This study investigates the connection between stress and AD biomarkers in a biracial cohort.Objective: Establish biomarker evidence for the observed association between stress and AD, especially in AA.Methods: A cross-sectional study (n = 364, 41.8% AA) administering cognitive tests and the perceived stress scale (PSS) questionnaire. A subset (n = 309) provided cerebrospinal fluid for measurement of Aβ42, Tau, Ptau, Tau/Aβ42 (TAR), and Ptau/Aβ42 (PTAR). Multivariate linear regression, including factors that confound racial differences in AD, was performed.Results: Higher PSS scores were associated with higher Ptau (β= 0.43, p = 0.01) and PTAR (β= 0.005, p = 0.03) in AA with impaired cognition (mild cognitive impairment).Conclusion: Higher PSS scores were associated with Tau-related AD biomarker indices in AA/MCI, suggesting a potential biological connection for stress with AD and its racial disparity. [ABSTRACT FROM AUTHOR]

Background: Both sleep quality and depression could affect cognitive performance in older adults. Previous studies have suggested that there are bi-directional relationships between sleep quality and depression. Possibly, the influence of sleep quality on cognition is partly mediated by depression, and vice versa.Objective: We aimed to assess the mediation effects of sleep quality and depression on each other's relationship with various cognitive functions in non-demented older adults.Methods: Correlations were examined among sleep quality indices, depressive severity score, and five cognitive functions in 206 cognitively normal (CN) older adults and all participants that included these CN and 40 mild cognitive impairment (MCI) individuals. We then analyzed the mediation effects for the significant cognitive correlations of sleep disturbance and depression using the bias-corrected Bootstrap method in the two populations.Results: Both sleep disturbance and depression were significantly correlated with memory recall and processing speed. In CN, depression could mediate the relationships of sleep disturbance with both cognitive functions, while sleep disturbance could only mediate the relationship of depression with processing speed, but not memory recall. However, in all participants, sleep disturbance could mediate the relationships of depression with both cognitive functions.Conclusion: Different mediation effects in the two models in CN older adults might suggest differential mechanisms underlying the pathways from sleep disturbance and depression to various cognitive functions. The mediation results in all participants might indicate that the mechanisms underlying the pathways from sleep disturbance and depression to memory recall were different between MCI and CN older adults. [ABSTRACT FROM AUTHOR]

Background: The role of infectious agents in the development of Alzheimer's disease (AD) has long been debated, however, uncertainties still persist.Objective: We aimed to illuminate the associations between infectious agents and risk of AD comprehensively.Methods: Studies examining the associations between AD and infectious agents were identified through a systematic search of PubMed, Embase, and Cochrane library. A random-effects meta-analysis was conducted. Publication bias was explored using funnel plot.Results: Fifty-one studies were included in the systematic review, of which forty-seven studies with 108,723 participants and 4,039 AD cases were eligible for meta-analysis. Evidence based on case control studies demonstrated that Chlamydia pneumoniae [odds ratio (OR): 4.39, 95% CI = 1.81-10.67; I2 = 68%)], Human herpes virus-6 (OR: 3.97, 95% CI = 2.04-7.75; I2 = 0%, Epstein-Barr virus (OR:1.45, 95% CI = 1.00-2.08; I2 = 0%), Herpes simplex virus-1 (OR:1.34, 95% CI = 1.02-1.75; I2 = 0%), and the Herpesviridae family (OR:1.41, 95% CI = 1.15-1.74; I2 = 12%) infection were associated with a higher risk of AD. No significant evidence of publication bias was found.Conclusion: These findings strengthened the evidence that infection may play an important role in AD. Additional research is required to determine whether treatment strategies targeting infectious diseases to prevent AD are viable in the future. [ABSTRACT FROM AUTHOR]

Background: It is well-documented that African Americans have elevated risk for cognitive impairment and dementia in late life, but reasons for the racial disparities remain unknown. Stress processes have been linked to premature age-related morbidity, including Alzheimer's and related dementias (ADRD), and plausibly contribute to social disparities in cognitive aging.Objective: We examined the relationship between stressful life events and cognitive decline among African American and White participants enrolled in the Wisconsin Registry for Alzheimer's Prevention (WRAP).Methods: Linear mixed models including demographic, literacy, and health-related covariates were used to estimate (1) relationships between a life event index score and decline in cognitive test performance in two domains of executive function (Speed & Flexibility, Working Memory) and one domain of episodic memory (Verbal Learning & Memory) among 1,241 WRAP enrollees, stratified by race, and (2) contributions of stressful life events to racial differences in cognition within the full sample.Results: African Americans (N = 50) reported more stressful life events than Whites (N = 1,191). Higher stress scores associated with poorer Speed & Flexibility performance in both groups, though not with declines across time, and partially explained racial differentials in this domain. Among African Americans only, stressor exposure also associated with age-related decline in Verbal Learning & Memory. Stressor-cognition relationships were independent of literacy and health-related variables.Conclusions: Greater lifetime stress predicted poorer later-life cognition, and, in a small sample of African Americans, faster declines in a key domain of episodic memory. These preliminary findings suggest that future work in large minority aging cohorts should explore stress as an important source of modifiable, socially-rooted risk for impairment and ADRD in African Americans, who are disproportionately exposed to adverse experiences across the life course. [ABSTRACT FROM AUTHOR]

Background: Several environmental factors, including infectious agents, have been suggested to cause Alzheimer's disease (AD). Cytomegalovirus (CMV) has been associated with AD in several recent studies.Objective: To investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD.Methods: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years), taken an average of 9.6 years before AD diagnosis, and 360 age-, sex-, cohort-, and sampling date matched dementia-free controls were analyzed to detect anti-CMV (immunoglobulin [Ig] G and IgM), group-specific anti-HSV (IgG and IgM), and specific anti-HSV1 and HSV2 IgG antibodies by enzyme-linked immunosorbent assays. AD cases and dementia-free controls were compared using conditional logistic regression analyses.Results: The presence of anti-CMV IgG antibodies did not increase the risk of AD (odds ratio [OR], 0.857; p = 0.497). Among AD cases, an association between CMV and HSV1 carriage was detected (OR 7.145, p < 0.001); in a conditional logistic regression model, the interaction between CMV and HSV1 was associated with AD development (OR 5.662; p = 0.007).Conclusion: The present findings do not support a direct relationship between CMV infection and the development of AD; however, an interaction between CMV and HSV1 was found to be associated significantly with AD development. These findings suggest that CMV infection facilitates the development of HSV1-associated AD, possibly via its effects on the immune system. [ABSTRACT FROM AUTHOR]

Background: The Religious Orders Study and Rush Memory and Aging Project are both ongoing longitudinal clinical-pathologic cohort studies of aging and Alzheimer's disease (AD).Objectives: To summarize progress over the past five years and its implications for understanding neurodegenerative diseases.Methods: Participants in both studies are older adults who enroll without dementia and agree to detailed longitudinal clinical evaluations and organ donation. The last review summarized findings through the end of 2011. Here we summarize progress and study findings over the past five years and discuss new directions for how these studies can inform on aging and AD in the future.Results: We summarize 1) findings on the relation of neurobiology to clinical AD; 2) neurobiologic pathways linking risk factors to clinical AD; 3) non-cognitive AD phenotypes including motor function and decision making; 4) the development of a novel drug discovery platform.Conclusion: Complexity at multiple levels needs to be understood and overcome to develop effective treatments and preventions for cognitive decline and AD dementia. [ABSTRACT FROM AUTHOR]