Background: White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. Methods: One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aβ. The relationships of total and regional WMH to age, vascular risk factors, cortical Aβ, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old). Results: WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aβ, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aβ load in the models did not alter the results, and there was no interaction between WMH and Aβ on cognition. Conclusion: WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aβ load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH.

Sleep-disordered breathing (SDB) is a respiratory disorder characterized by recurrent upper airway collapse during sleep, associated with intermittent hypoxia and sleep fragmentation.^1,2 It affects 30% to 80% of older adults who are cognitively unimpaired, depending on the SDB definition criteria.^3,4 Patients with a clinical diagnosis of Alzheimer disease (AD) are even more likely to suffer from SDB,⁵ and untreated SDB is associated with cognitive decline and conversion to the Alzheimer clinical syndrome at a younger age.^6-8

Around 40% of dementia risk is attributable to modifiable risk factors such as physical inactivity, hypertension, diabetes and obesity. Recently, sleep disorders, including obstructive sleep apnea (OSA), have also been considered among these factors. However, despite several epidemiological studies investigating the link between OSA and cognitive decline, there is still no consensus on whether OSA increases the risk of dementia or not. Part of the heterogeneity observed in previous studies might be related to some individual characteristics that modulate the association between OSA and cognitive decline. In this narrative review, we present these individual characteristics, namely, age, sex, menopause, obesity, diabetes mellitus, hypertension, cardiovascular diseases, smoking, excessive alcohol consumption, depression, air pollution, Apolipoprotein E ε4 allele, physical activity, and cognitive reserve. To date, large cohort studies of OSA and cognitive decline tended to statistically control for the effects of these variables, but whether they interact with OSA to predict cognitive decline remains to be elucidated. Being able to better predict who is at risk of cognitive decline when they have OSA would improve clinical management and treatment decisions, particularly when patients present relatively mild OSA.

Aging is associated with progressive cerebral volume and glucose metabolism decreases. Conditions such as stress and sleep difficulties exacerbate these changes and are risk factors for Alzheimer’s disease. Meditation practice, aiming towards stress reduction and emotion regulation, can downregulate these adverse factors. In this pilot study, we explored the possibility that lifelong meditation practice might reduce age-related brain changes by comparing structural MRI and FDG-PET data in 6 elderly expert meditators versus 67 elderly controls. We found increased gray matter volume and/or FDG metabolism in elderly expert meditators compared to controls in the bilateral ventromedial prefrontal and anterior cingulate cortex, insula, temporo-parietal junction, and posterior cingulate cortex /precuneus. Most of these regions were also those exhibiting the strongest effects of age when assessed in a cohort of 186 controls aged 20 to 87 years. Moreover, complementary analyses showed that these changes were still observed when adjusting for lifestyle factors or using a smaller group of controls matched for education. Pending replication in a larger cohort of elderly expert meditators and longitudinal studies, these findings suggest that meditation practice could reduce age-associated structural and functional brain changes.

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.