Subjective Cognitive Decline and Nighttime Sleep Alterations, a Longitudinal Analysis.

Objective: The aim of this study was to analyze quantitative sleep changes and their implication on subjective cognitive decline (SCD). Objective sleep patterns were investigated by an actigraph and recorded at the baseline and 2-year after in order to examine specific sleep alterations in SCD. Background: Sleep disorders are very common among average elderly adults and an altered sleep pattern is known to be a risk factor for future development of mild cognitive impairment (MCI) and dementia. Recent studies have shown how sleep is objectively altered in average senior adults with SCD, without any other significant change in cognition and behavior or brain structure. Considering that both SCD and disrupted sleep are risk factors for future MCI and dementia, with sleep only as a modifiable risk factor, further research is required to deeply investigate the interaction between sleep and SCD. Methods: Among 70 community-dwelling elderly individuals who had been enrolled at baseline, 35 (64.6 ± 5.6 years, 15 M/20 F) underwent a complete neuropsychological battery and 1-week wrist actigraphy recording 2 years later during the follow-up stage. Individuals were divided into two groups according to their SCD Questionnaire (SCD-Q) score. Sleep hours, sleep efficiency and onset latency, napping and time awake after sleep onset (WASO) were collected. All individuals underwent structural magnetic resonance imaging (MRI) examination to exclude brain disorders. Data collection was performed at baseline and after 2 years at the follow-up phase. Results: A significantly different night sleep time between the two groups was observed: SCD showed a lower total sleep time (TST) than non-SCD subjects. Moreover, a total time spent in bed (TIB) was significantly lower in SCD subjects over 2 years of observation. Conclusions: Objective changes over time of the sleep pattern, specifically TIB and TST, are present in SCD individuals. The results of the study show that sleep alterations are common in SCD and underline the clinical importance of screening in order to assess sleep alterations as well as improve sleep in average adults with SCD complaints.

Modifications in resting state functional anticorrelation between default mode network and dorsal attention network: comparison among young adults, healthy elders and mild cognitive impairment patients.

Resting state brain activity incorporates different components, including the Default Mode Network and the Dorsal Attention Network, also known as task-negative network and task-positive network respectively. These two networks typically show an anticorrelated activity during both spontaneous oscillations and task execution. However modifications of this anticorrelated activity pattern with age and pathology are still unclear. The present study aimed to investigate differences in resting state Default Mode Network-Dorsal Attention Network functional anticorrelation among young adults, healthy elders and Mild Cognitive Impairment patients. We retrospectively enrolled in this study 27 healthy young adults (age range: 25-35 y.o.; mean age: 28,5), 26 healthy elders (age range: 61-72 y.o.; mean age: 65,1) and 17 MCI patients (age range 64-87 y.o.; mean age: 73,6). Mild Cognitive Impairment patients were selected following Petersen criteria. All participants underwent neuropsychological evaluation and resting state functional Magnetic Resonance Imaging. Spontaneous anticorrelated activity between Default Mode Network and Dorsal Attention Network was observed in each group. This anticorrelation was significantly decreased with age in most Default Mode Network-Dorsal Attention Network connections (p < 0.001, False Discovery Rate corrected). Moreover, the anticorrelation between the posterior cingulate cortex node of the Default Mode Network and the right inferior parietal sulcus node of the Dorsal Attention Network was significantly decreased when comparing Mild Cognitive Impairment with normal elders (p < 0.001, False Discovery Rate corrected). The functional connectivity changes in patients were not related to significant differences in grey matter content. Our results suggest that a reduced anticorrelated activity between Default Mode Network and Dorsal Attention Network is part of the normal aging process and that Mild Cognitive Impairment status is associated with more evident inter-networks functional connectivity changes.

Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer's disease.

Neuropathological and in vivo studies have revealed a tight relationship between tau pathology and cognitive impairment across the Alzheimer's disease spectrum. However, tau pathology is also intimately associated with neurodegeneration and amyloid pathology. The aim of the present study was therefore to assess whether grey matter atrophy and amyloid pathology contribute to the relationship between tau pathology, as measured with 18F-AV-1451-PET imaging, and cognitive deficits in Alzheimer's disease. We included 40 amyloid-positive patients meeting criteria for mild cognitive impairment due to Alzheimer's disease (n = 5) or probable Alzheimer's disease dementia (n = 35). Twelve patients additionally fulfilled the diagnostic criteria for posterior cortical atrophy and eight for logopenic variant primary progressive aphasia. All participants underwent 3 T magnetic resonance imaging, amyloid (11C-PiB) positron emission tomography and tau (18F-AV-1451) positron emission tomography, and episodic and semantic memory, language, executive and visuospatial functions assessment. Raw cognitive scores were converted to age-adjusted Z-scores (W-scores) and averaged to compute composite scores for each cognitive domain. Independent regressions were performed between 18F-AV-1451 binding and each cognitive domain, and we used the Biological Parametric Mapping toolbox to further control for local grey matter volumes, 11C-PiB uptake, or both. Partial correlations and causal mediation analyses (mediation R package) were then performed in brain regions showing an association between cognition and both 18F-AV-1451 uptake and grey matter volume. Our results showed that decreased cognitive performance in each domain was related to increased 18F-AV-1451 binding in specific brain regions conforming to established brain-behaviour relationships (i.e. episodic memory: medial temporal lobe and angular gyrus; semantic memory: left anterior temporal regions; language: left posterior superior temporal lobe and supramarginal gyrus; executive functions: bilateral frontoparietal regions; visuospatial functions: right more than left occipitotemporal regions). This pattern of regional associations remained essentially unchanged-although less spatially extended-when grey matter volume or 11C-PiB uptake maps were added as covariates. Mediation analyses revealed both direct and grey matter-mediated effects of 18F-AV-1451 uptake on cognitive performance. Together, these results show that tau pathology is related in a region-specific manner to cognitive impairment in Alzheimer's disease. These regional relationships are weakly related to amyloid burden, but are in part mediated by grey matter volumes. This suggests that tau pathology may lead to cognitive deficits through a variety of mechanisms, including, but not restricted to, grey matter loss. These results might have implications for future therapeutic trials targeting tau pathology.

Sleep changes without medial temporal lobe or brain cortical changes in community-dwelling individuals with subjective cognitive decline.

INTRODUCTION: Subjective cognitive decline (SCD) is a risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Although sleep has been shown to be altered in MCI and AD, little is known about sleep in SCD. METHODS: Seventy cognitively normal community-dwelling participants were classified as SCD (32) or controls (38) using the Subjective Cognitive Decline Questionnaire. Sleep was assessed using actigraphy and diaries. FreeSurfer was used for performing medial temporal lobes (MTLs) and brain cortical parcellation of 3T magnetic resonance images. Multiple regression models were used to assess the presence of sleep, MTL, or regional cortical differences between groups. RESULTS: Objective sleep was disrupted in SCD participants, which showed increased nighttime wakefulness and reduced sleep efficiency. No group differences emerged in subjective sleep or magnetic resonance imaging outcomes. DISCUSSION: Objective sleep resulted disrupted in community-dwelling SCD, without any subjective sleep or cortical change. Sleep assessment/intervention in SCD might help prevent/delay AD onset.