Search

Background: White matter hyperintensities (WMH) are very frequent in ageing and related to worse cognition. Recent studies suggest that WMH in the corpus callosum (CC) are particularly relevant in neurocognitive disorders, as they are strongly associated with lower cognitive performance, as well as amyloid and neurodegeneration biomarkers. This study examined whether WMH in subregions of the CC (genu, body, splenium) affect cross‐sectional and long‐term longitudinal (up to 5 years) cognitive performance in patients recruited from a memory clinic. Method: This study included memory clinic outpatients from the MEMORA cohort who had a brain MRI (T1 and FLAIR scans) within 6 months of the baseline visit. QyScore® software was used for the automatic segmentation of WMH in the CC and hippocampal volumes (HP). The cross‐sectional and longitudinal relationships between regional WMH in the CC and cognitive performance, as measured with the mini‐mental state examination (MMSE), were assessed using multivariable linear regressions and mixed models. Result: Among 236 patients included (mean age 76.2±8.8 years old; mean MMSE 23.6±4.9), 111 were diagnosed with probable Alzheimer’s disease (AD), 20 with vascular cognitive impairment (VCI), 22 with mixed AD‐VCI, 18 with another neurological disease and 65 with a subjective cognitive complaint. Cross‐sectional analyses disclosed that higher WMH in the splenium of the CC were associated with reduced MMSE (p=0.03, n=199) after adjustment for diagnosis and education. The relationship did not remain significant after adjustment for HP and total WMH. Longitudinal analyses with a follow‐up up to 5 years showed that the MMSE declined faster in patients with higher WMH in the splenium of the CC (p<0.001, n=143) after adjustment for education, diagnosis, HP and total WMH (Figure). WMH in the genu and in the body of the CC were not associated with MMSE decline (respectively p=0.92 and p=0.23, n=124, Figure). Conclusion: WMH in the splenium of the CC were associated with cognitive decline, whereas WMH in the genu and the body were not. This study highlights the clinical relevance of posterior CC WMH in a memory clinic population. [ABSTRACT FROM AUTHOR]

Background: Given the burden related to dementia, identifying prevention targets against cognitive aging and Alzheimer's disease (AD) and related disorders is of high interest. While factors of resilience, i.e. education, physical or cognitive activity, or social network, are thought to mitigate the effect of cerebral damage on cognition, mechanisms involved are not well understood. This work thus aims to investigate the pathways involved in the association between resilience and cognition. Method: Data were collected as part of the Memento study, a French nationwide cohort including patients from 28 memory clinics with either isolated cognitive complaints or mild cognitive impairment. Factors contributing to resilience, such as education level, salary, physical activity, leisure activities, or social network, as well as MRI markers of brain health were collected at baseline. AD cerebrospinal fluid (CSF) biomarkers were assessed in a subsample (n=410). Based on resilience factors, we established a global resilience score using a latent variable from a structural equation model. Structural equation models were also used to evaluate cross‐sectional pathways between resilience, brain ageing biomarkers in relation to cognition, taking into account potential confounders (Figure). Estimates from latent variables were standardized and results reported are for one SD of resilience. Result: Participants' mean age was 70.9 years old, 62% were women, 28% were APOE‐ε4 carriers, and 59% had a CDR score of 0.5. Resilience score obtained for each participants, ranged from ‐2.28 to 2.73. AD CSF biomarkers were all significantly associated with worse cognition. Higher resilience was significantly associated with higher cognitive performances (total βres_cog=0.569, p<.0001). In addition to a direct effect on cognition (direct βres_cog=0.519, p<.0001), this association was partly mediated by an indirect effect of resilience on cognition (indirect βres_cog=0.050, p<.0001) through lower neurodegeneration (direct βres_nd=‐0.128, p<.0001). White matter hyperintensities volume, CSF Aβ42/Aβ40 ratio, and CSF phosphorylated tau were not involved in the association between resilience and cognition. Conclusion: Resilience preserves cognitive functions both directly and indirectly through an apparent protection against neurodegeneration. Beside, AD and small vessel disease markers are not associated with resilience and they do not mediate the protective effect of resilience on cognition. [ABSTRACT FROM AUTHOR]

Background: Brain white matter hyperintensities (WMH) are frequent in older adults, including cognitively unimpaired individuals and are associated to decreased cognitive performances. The prevalence of WMH and their links with cognitive performance and with cortical β‐amyloid (Aβ) burden have been rarely assessed in younger adults. The aim of this study was to assess the impact of WMH in younger and older cognitively unimpaired adults on cognitive performances and the possible interaction with cortical β‐amyloid (Aβ) burden. Method: Two hundred and seventy‐two cognitively unimpaired adults from the community (from the IMAP study and the Age‐Well trial) were enrolled and age‐stratified in 86 younger adults (YA; ≤60 years old) and 187 older adults (OA; >60 years old). All participants underwent i) a comprehensive neuropsychological assessment allowing to obtain composite scores of episodic memory, processing speed, working memory, executive functions, and global cognition; ii) brain structural T1 and FLAIR MRI scans used for automatic segmentation of WMH volumes; and iii) a Florbetapir‐PET scan to measure cortical Aβ. Within each group, the relationships of total and regional WMH to age and cognition were assessed, as well as the impact of cortical Aβ on these relationships. Result: WMH increased with age in both groups but more sharply in OA than YA, particularly in the parietal lobe. Higher WMH volume was associated to worse cognitive performances in both groups. Particularly, working memory, processing speed and global cognition were negatively associated with global and regional WMH in YA and executive functions were negatively associated to occipital WMH in OA. Cortical Aβ differentially impacts the links between WMH and cognition in YA versus OA. Conclusion: WMH volume increases with age and is negatively associated to cognitive performances including in YA. This study argues for the clinical relevance of WMH even in middle age. [ABSTRACT FROM AUTHOR]

Diagnosis of cognitive disorders is at medical and ethical stake. The aim of an qualitative study based on interviews was to explore the views of general practitioners on this diagnosis. General practitioners are ambivalent about the relevance and temporality of the diagnosis of cognitive disorders, which could be resolved by a shared decision making at each stage of the diagnostic approach., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)