Sleep fragmentation, microglial aging, and cognitive impairment in adults with and without Alzheimer’s dementia.
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ABSTRACT:
SUBMITTER: Kaneshwaran K
PROVIDER: S-EPMC6905859 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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Project description:BackgroundMild cognitive impairment and cognitive impairment, no dementia, are emerging terms that encompass the clinical state between normal cognition and dementia in elderly people. Controversy surrounds their characterization, definition and application in clinical practice. In this article, we provide physicians with practical guidance on the definition, diagnosis and treatment of mild cognitive impairment and cognitive impairment, no dementia, based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006.MethodsWe developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that had mild cognitive impairment or cognitive impairment, no dementia, as the outcome. Subsequent to the conference, we searched for additional articles published between January 2006 and January 2008. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care.ResultsWe identified 2483 articles, of which 314 were considered to be relevant and of good or fair quality. From a synthesis of the evidence in these studies, we made 16 recommendations. In brief, family physicians should be aware that most types of dementia are preceded by a recognizable phase of mild cognitive decline. They should be familiar with the concepts of mild cognitive impairment and of cognitive impairment, no dementia. Patients with these conditions should be closely monitored because of their increased risk for dementia. Leisure activities, cognitive stimulation and physical activity could be promoted as part of a healthy lifestyle in elderly people and those with mild cognitive impairment. Vascular risk factors should be treated optimally. No other specific therapies can yet be recommended.InterpretationPhysicians will increasingly see elderly patients with mild memory loss, and learning an approach to diagnosing states such as mild cognitive impairment is now warranted. Close monitoring for progression to dementia, promotion of a healthy lifestyle and treatment of vascular risk factors are recommended for the management of patients with mild cognitive impairment.
| S-EPMC2335177 | biostudies-literature
Project description:Importance:Substantial heterogeneity and uncertainty exist in the observed associations between alcohol consumption and dementia. Objective:To assess the association between alcohol consumption and dementia and the roles of mild cognitive impairment (MCI) and apolipoprotein E ?4 (APOE E4) genotype in modifying this association. Design, Setting, and Participants:This cohort study used data from the Ginkgo Evaluation of Memory Study, conducted from 2000 to 2008 among US community-dwelling participants. This study analyzed 3021 participants aged 72 years and older who were free of dementia. Data analysis was performed from 2017 to 2018. Exposures:Self-reported alcohol consumption, drinking frequency, and quantity. Main Outcomes and Measures:Using multivariable proportional hazards regression and linear mixed models, the risk of dementia and the rate of change over time in the Modified Mini-Mental State Examination were estimated. Results:Among 3021 participants, the median (interquartile range) age was 78 (76-80) years; 1395 (46.2%) were female. During a median (interquartile range) follow-up of 6.0 (4.9-6.5) years, 512 cases of dementia occurred. For 7.1 to 14.0 drinks per week compared with less than 1.0 drink per week, the hazard ratios for dementia were 0.63 (95% CI, 0.38-1.06) among 2548 participants without MCI and 0.93 (95% CI, 0.47-1.84) among?473 participants with MCI. Among participants with MCI, the hazard ratio for dementia was 1.72 (95% CI, 0.87-3.40) for more than 14.0 drinks per week compared with less than 1.0 drink per week. The association of alcohol intake with dementia differed for participants with and without baseline MCI (P for interaction?=?.03). Among participants without MCI, daily low-quantity drinking was associated with lower dementia risk than infrequent higher-quantity drinking (hazard ratio, 0.45; 95% CI, 0.23-0.89; P =?.02). Findings were consistent when stratified by sex, age, and APOE E4 genotype. Compared with drinking less than 1.0 drink per week, complete abstention (in participants without MCI) and the consumption of more than 14.0 drinks per week (in participants with MCI) were associated with lower Modified Mini-Mental State Examination scores (mean difference at follow-up compared with baseline, -0.46 point [95% CI, -0.87 to -0.04 point] and -3.51 points [95% CI, -5.75 to -1.27 points], respectively). Conclusions and Relevance:In this study, complete abstention and consuming more than 14.0 drinks per week (compared with drinking <1.0 drink per week) were associated with lower cognitive scores among participants aged 72 years and older. Particular caution is needed among individuals with MCI who continue to drink alcohol.
| S-EPMC6777245 | biostudies-literature
Project description:The relationship between mild behavioral impairment (MBI) and Alzheimer's disease (AD) is intricate and still not well investigated. The purpose of the study is to examine the roles of the AD imaging pathologies in modulating the associations of MBI with cognitive impairments. We analyzed 1129 participants (563 [49.86%] female), who had measures of Neuropsychiatric Inventory Questionnaire (NPI-Q), cognition, and amyloid PET AD biomarkers from the Alzheimer's disease Neuroimaging Initiative (ADNI). We assess the longitudinal neuropathological and clinical correlates of baseline MBI via linear mixed effects and Cox proportional hazard models. The mediation analyses were used to test the mediation effects of AD pathologies on cognition. We found that MBI was associated with worse global cognition as represented by Mini-Mental State Examination (MMSE) (p < 0.001), and higher β-amyloid burden (p < 0.001). β-amyloid partially mediated the effects of MBI on cognition with the mediation percentage varied from 14.67 to 40.86% for general cognition, memory, executive, and language functions for non-dementia individuals. However, no significant associations were discovered between MBI and tau burden or neurodegeneration. Furthermore, longitudinal analyses revealed that individuals with MBI had a faster increase in brain amyloid burden (p < 0.001) and a higher risk of clinical conversion (HR = 2.42, 95% CI = 1.45 to 4.01 p < 0.001). In conclusion, MBI could be an imperative prediction indicator of clinical and pathological progression. In addition, amyloid pathologies might partially mediate the influences of MBI on cognitive impairments and AD risk.
| S-EPMC8580970 | biostudies-literature
Project description:Introduction:Sleep disturbances are increasingly recognized as a risk factor for Alzheimer's disease. However, no study has assessed the relationships between objective sleep fragmentation (SF) and brain and cognitive integrity across different cognitive stages, from cognitively unimpaired elderly subjects to patients with subjective cognitive decline and/or mild cognitive impairment. Methods:30 cognitively unimpaired elderly participants and 36 patients with subjective cognitive decline and/or mild cognitive impairment underwent a neuropsychological evaluation, structural MRI, 18F-fluorodeoxyglucose, and 18F-florbetapir-PET scans, and an actigraphy recording over a minimum of six consecutive nights. Multiple regression and mediation analyses were performed between SF parameters, neuroimaging data, and cognitive scores. Results:In cognitively unimpaired elderly participants, SF intensity mediated the association between frontohippocampal hypometabolism and lower executive functioning. Moreover, to a lower extent, increased SF variability was related to thalamic atrophy and ventromedial prefrontal amyloid burden. However, in patients with subjective cognitive decline and/or mild cognitive impairment, SF no longer contributed to the expression of cognitive deficits. Discussion:These findings suggest that SF may directly contribute to lower cognitive performance in cognitively unimpaired elderly subjects. Therefore, treating sleep disturbances before the onset of cognitive deficits may help to cope with brain alterations and maintain cognitive functioning.
| S-EPMC6369144 | biostudies-literature
Project description:Patients with Parkinson's disease (PD) frequently experience disrupted sleep, and several sleep abnormalities are associated with an increased risk of incident PD. However, there are few data concerning the relationship between objectively quantified sleep disruption and the cardinal histopathological features of PD, especially in individuals without clinical PD.We studied 269 older adults without PD who had participated in the Rush Memory and Aging Project and undergone uniform structured neuropathologic evaluations upon death. Sleep fragmentation was measured using actigraphy. Logistic regression models examined the associations of sleep fragmentation proximate to death with the burden of Lewy body pathology and substantia nigra neuron loss.Greater sleep fragmentation was associated with the presence of Lewy body pathology (odds ratio 1.40; 95% confidence interval 1.05-1.86; P = .02) and substantia nigra neuron loss (odds ratio 1.43; 95% confidence interval 1.10-1.88; P = .008) and a higher odds of a pathological diagnosis of PD (odds ratio 2.04; 95% confidence interval 1.34-3.16; P = .0009). These associations were independent of motor features of parkinsonism, demographic characteristics, and a wide range of medical co-morbidities.Sleep fragmentation is associated with PD pathology in older adults without PD. These results suggest that sleep fragmentation may be a marker of or risk factor for PD pathology in older adults without PD. © 2017 International Parkinson and Movement Disorder Society.
| S-EPMC5778902 | biostudies-literature
Project description:Amyloid ? (A?) peptides are important components of plaques in patients with Alzheimer's disease (AD). Recent studies suggest that a low plasma ratio of A?42 to A?40 may precede the development of the sporadic form of AD. The aim of this study was to establish reference intervals for plasma A? in Korean adults. A total of 370 apparently healthy individuals (181 males and 189 females aged 40-69 yr) without cognitive impairment were enrolled. Plasma concentrations of A?40 and A?42 were measured by using a human amyloid ? assay kit (Immuno-Biological Laboratories, Japan). Reference intervals were established according to the "CLSI guidelines for defining, establishing, and verifying reference intervals in the clinical laboratory". There was no need to partition the data with respect to gender or age group. The 95th percentile reference intervals for A?40 and A?42 were 127-331 pg/mL and 2.31-19.84 pg/mL, respectively. The reference interval for the A?42/A?40 ratio was 0.011-0.092. Plasma A? concentrations obtained in this study could be used as reference intervals for clinical purposes.
| S-EPMC5011114 | biostudies-other
Project description:OBJECTIVES:Physical activity (PA) is a modifiable health behavior that can protect against age-related gray matter atrophy and cognitive dysfunction. Current studies of PA and gray matter failed to utilize device measures of PA and do not focus on adults >80 years. Thus, the purpose of this secondary analysis was to examine cross-sectional associations between accelerometer lifestyle PA and (a) gray matter volumes and (b) cognitive function, controlling for demographics, and health status. METHOD:Participants were 262 older adults without dementia or mild cognitive impairment from Rush Memory and Aging Project, an epidemiological cohort study. Participants wore an accelerometer to assess total daily lifestyle PA, and completed anatomical magnetic resonance imaging to assess gray matter volumes and a neurocognitive test battery to assess cognitive function. RESULTS:Multivariate linear regression indicated that higher levels of total daily lifestyle PA was significantly related to larger gray matter volumes, F(2, 215) = 3.61, p = .027, including subcortical gray matter (? = 0.17, p = .007) and total gray matter (? = 0.11, p = .049), with no significant associations between lifestyle PA and cognitive function. DISCUSSION:These findings may inform future lifestyle PA interventions in order to attenuate age-related gray matter atrophy.
| S-EPMC6748751 | biostudies-literature
Project description:Objective: Recent research suggests that sleep disorders or changes in sleep stages or EEG waveform precede over time the onset of the clinical signs of pathological cognitive impairment (e.g., Alzheimer's disease). The aim of this study was to identify biomarkers based on EEG power values and spindle characteristics during sleep that occur in the early stages of mild cognitive impairment (MCI) in older adults. Methods: This study was a case-control cross-sectional study with 1-year follow-up of cases. Patients with isolated subjective cognitive complaints (SCC) or MCI were recruited in the Bordeaux Memory Clinic (MEMENTO cohort). Cognitively normal controls were recruited. All participants were recorded with two successive polysomnography 1 year apart. Delta, theta, and sigma absolute spectral power and spindle characteristics (frequency, density, and amplitude) were analyzed from purified EEG during NREM and REM sleep periods during the entire second night. Results: Twenty-nine patients (8 males, age = 71 ± 7 years) and 29 controls were recruited at T0. Logistic regression analyses demonstrated that age-related cognitive impairment were associated with a reduced delta power (odds ratio (OR) 0.072, P < 0.05), theta power (OR 0.018, P < 0.01), sigma power (OR 0.033, P < 0.05), and spindle maximal amplitude (OR 0.002, P < 0.05) during NREM sleep. Variables were adjusted on age, gender, body mass index, educational level, and medication use. Seventeen patients were evaluated at 1-year follow-up. Correlations showed that changes in self-reported sleep complaints, sleep consolidation, and spindle characteristics (spectral power, maximal amplitude, duration, and frequency) were associated with cognitive impairment (P < 0.05). Conclusion: A reduction in slow-wave, theta and sigma activities, and a modification in spindle characteristics during NREM sleep are associated very early with a greater risk of the occurrence of cognitive impairment. Poor sleep consolidation, lower amplitude, and faster frequency of spindles may be early sleep biomarkers of worsening cognitive decline in older adults.
| S-EPMC6424890 | biostudies-literature
Project description:ObjectiveEvidence of a relation between use of lipid lowering drugs and cognitive outcomes is mixed. This study aimed to test the association between use of statins and incidence of dementia and cognitive impairment without dementia (CIND) over 5 years of follow-up.MethodsData were from a population-based cohort study comprising 1,789 older Mexican Americans. All participants had cognitive and clinical evaluations performed every 12 to 15 months. Participants who fell below specified cutpoints on cognitive tests were then evaluated clinically. Dementia diagnoses were finalized by an adjudication team. A total of 1,674 participants free of dementia/CIND at baseline were included in these analyses. Statin use was verified at each participant's home by medicine cabinet inspection. Cox proportional hazards models were used to evaluate the association between statin use and incidence of dementia/CIND.ResultsOverall, 452 of 1,674 participants (27%) took statins at any time during the study. Over the 5-year follow-up period, 130 participants developed dementia/CIND. In Cox proportional hazards models adjusted for education, smoking status, presence of at least one APOE epsilon4 allele, and history of stroke or diabetes at baseline, persons who had used statins were about half as likely as those who did not use statins to develop dementia/CIND (HR = 0.52; 95% CI 0.34, 0.80).ConclusionStatin users were less likely to have incident dementia/cognitive impairment without dementia during a 5-year follow-up. These results add to the emerging evidence suggesting a protective effect of statin use on cognitive outcomes.
| S-EPMC2676946 | biostudies-literature
Project description:Depressive symptoms are associated with cognitive-functional impairment in normal aging older adults (NA). However, less is known about this effect on people with mild Cognitive Impairment (MCI) and mild Alzheimer's disease dementia (AD). We investigated this relationship along with the NA-MCI-AD continuum by reanalyzing a previously published dataset. Participants (N = 274) underwent comprehensive neuropsychological assessment including measures of Executive Function, Language/Semantic Memory, Episodic Memory, Visuospatial Abilities, Activities of Daily Living (ADL), and the Geriatric Depression Scale. MANOVA, logistic regression and chi-square tests were performed to assess the association between depression and cognitive-functional performance in each group. In the NA group, depressed participants had a lower performance compared to non-depressed participants in all cognitive and functional domains. However, the same pattern was not observed in the MCI group or in AD. The results suggest a progressive loss of association between depression and worse cognitive-functional performance along the NA-MCI-AD continuum.
| S-EPMC4727063 | biostudies-literature