Association between insomnia and cognitive performance, gray matter volume, and white matter microstructure in cognitively unimpaired adults

Abstract

Background: Mounting evidence links poor sleep quality with a higher risk of late-life dementia. However, the structural and cognitive correlates of insomnia are still not well understood. The study aims were to characterize the cognitive performance and brain structural pattern of cognitively unimpaired adults at increased risk for Alzheimer's disease (AD) with insomnia. Methods: This cross-sectional study included 1683 cognitively unimpaired middle/late-middle-aged adults from the ALFA (ALzheimer and FAmilies) study who underwent neuropsychological assessment, T1-weighted structural imaging (n = 366), and diffusion-weighted imaging (n = 334). The World Health Organization's World Mental Health Survey Initiative version of the Composite International Diagnostic Interview was used to define the presence or absence of insomnia. Multivariable regression models were used to evaluate differences in cognitive performance between individuals with and without insomnia, as well as potential interactions between insomnia and the APOE genotype. Voxel-based morphometry and tractbased spatial statistics were used to assess between-group differences and potential interactions between insomnia and the APOE genotype in gray matter volume and white matter diffusion metrics. Results: Insomnia was reported by 615 out of 1683 participants (36.5%), including 137 out of 366 (37.4%) with T1-weighted structural imaging available and 119 out of 334 (35.6%) with diffusion-weighted imaging. Individuals with insomnia (n = 615) performed worse in executive function tests than non-insomniacs and displayed lower gray matter volume in left orbitofrontal and right middle temporal cortex, bilateral precuneus, posterior cingulate cortex and thalamus, higher gray matter volume in the left caudate nucleus, and widespread reduction of mean and axial diffusivity in right hemisphere white matter tracts. Insomnia interacted with the APOE genotype, with APOE-ε4 carriers displaying lower gray matter volumes when insomnia was present, but higher volumes when insomnia was not present, in several gray matter regions, including the left angular gyrus, the bilateral superior frontal gyri, the thalami, and the right hippocampus.

Exercise and Fitness Neuroprotective Effects: Molecular, Brain Volume and Psychological Correlates and Their Mediating Role in Healthy Late-Middle-Aged Women and Men

“…Men performing more exercise reported higher sleep efficiency and fewer sleep disturbances and those with higher levels of CRF presented fewer depressive symptoms and better general mood. In mediation analyses, and in accordance with previous papers relating diminished precuneus with insomnia (Grau-Rivera et al, 2020 ) and sleep restriction (Long et al, 2020 ), we found that greater volume of the precuneus in men mediated the higher CRF-better subjective sleep quality association. Surprisingly, in our sample, physical activity was not related with these behavioral outcomes in women.…”

Gender Difference in the Prevalence of Insomnia: A Meta-Analysis of Observational Studies

“…Several diagnostic criteria for insomnia have been widely used in clinical practice, including the International Classification of Sleep Disorder (ICSD), the DSM, and International Classification of Diseases (ICD) systems (e.g., codes 307.41, 307.42, or 780.52 in the ICD-9) (4-9). In addition, certain standardized diagnostic instruments for insomnia based on the ICD/DSM criteria have been developed, such as the World Health Organization Composite International Diagnostic Interview (CIDI) (10)(11)(12)(13).…”

Is Sleep Disruption a Cause or Consequence of Alzheimer’s Disease? Reviewing Its Possible Role as a Biomarker

“…A recent study performed in cognitively unimpaired adults aged between 45 and 75, found that insomnia patients presented decreases in grey matter volume in AD-related areas, that concur with other studies. Furthermore, they found greater volume in the left caudate in these subjects, which can also be seen in presymptomatic carriers of an AD genetic mutation [21]. Finally, a very recent study in middle-aged, cognitively unimpaired adults found lower grey matter volumes in the left angular gyrus, the bilateral superior frontal gyri, the thalami, and the right hippocampus in insomniac APOE-ε4 carriers (AD's main risk factor) when compared to non-carriers with or without insomnia [21].This temporal and anatomical relationship could suggest that sleep disturbances may influence or exacerbate AD pathology and that improving sleep may help slow down its progression [22,23].…”