👤 Nathalie Villeneuve

The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for Alzheimer's disease (AD) and is linked to poorer cerebrovascular health. Cerebrovascular reactivity (CVR), an indicator of vascular reserve, and cerebral pulsatility (CP), a marker of vascular stiffness, are sensitive biomarkers of early vascular dysfunction associated with aging and AD. However, the relationship between APOE4 status and these cerebrovascular metrics remains unclear. This study investigated whether the APOE genotype influences longitudinal changes in CVR and CP, and their association with cognitive performance in cognitively unimpaired individuals. We utilized the PREVENT-AD cohort, including 101 APOE4 carriers (30 males and 71 females) and 152 non-APOE4 carriers (48 males and 104 females) aged 55 and older. Relative CVR and CP were derived from resting state functional magnetic resonance imaging data, with regional values extracted from cerebral arterial territories. Results indicated significant interactions between APOE4 status and relative CVR in the left middle cerebral artery and left posterior cerebral artery (PCA) territories. APOE4 status disaggregated analyses revealed that APOE4 carriers uniquely presented a significant decline in relative CVR within the left PCA. Furthermore, sex-specific effects were identified, with female APOE4 carriers having lower relative CVR in the right anterior cerebral artery territory compared to female non-carriers. Importantly, higher relative CVR was positively associated with better cognitive performance in APOE4 carriers. No significant effects of APOE4 status on CP were found. Together, these findings suggest that relative CVR may be an important early measure of cerebrovascular health and cognition in cognitively intact APOE4 carriers. Show less

An emerging approach in surgery is to propose prehabilitation programs to strengthen the patient's functional abilities before surgical interventions, thus helping them cope better with its consequences. In drug-resistant language-dominant temporal lobe epilepsy (LdTLE), surgical treatment carries a risk of increasing cognitive deficits, notably word-finding difficulties (anomia) and verbal memory difficulties that negatively impact personal, social, and occupational activities. In this study, we invited 15 LdTLE patients to enroll in a speech and language prehabilitation program adapted to the specifics of their difficulties, organized daily during the preoperative period. Naming performance (for trained and untrained words) was studied twice before prehabilitation, during prehabilitation, and 1 week and 6 months after surgery. Results were analyzed using a generalized linear mixed effects model. We found a significant effect of prehabilitation on trained items before surgery. Postoperatively, trained items showed a slight and nonsignificant performance increase compared to baseline, whereas untrained items showed a significant decline in the same comparison. We conclude that trained words were better protected from postsurgical decline than untrained words. Our research can contribute to patient support during surgical decision-making; ultimately, prehabilitation might be considered as part of individualized care. These encouraging results lay the groundwork for more detailed or powerful examinations of the protective effect of prehabilitation on language skills. Show less

Spondyloepimetaphyseal dysplasias (SEMD) represent a heterogeneous group of conditions composed of at least 15 well-defined entities. The classification is based on clinical, radiological and molecular findings. Among them, several conditions also include a mental retardation (MR) syndrome, namely Wolcott-Rallison syndrome, Dyggve-Melchior-Clausen syndrome (DMC) and lysosomal storage disorders. Here, we report on a novel form of SEMD with MR in two Pakistani sisters born to first-cousin parents. SEMD, MR, microcephaly, ataxia, facial dysmorphism and hirsutism of back and legs were noted in the two children. Skeletal findings included flat vertebral bodies with irregular vertebral plates, irregular and flared metaphyses with vertical striations, small and irregular epiphyses, small carpal bones and narrow iliac wings without lacy pelvis iliac crest. Similarities with DMC prompted us to test and eventually exclude the DMC gene, dymeclin, by direct sequencing. Similarly, we excluded the PAPSS2 gene (3'-alpha phosphoadenosine 5'-phosphosulphate synthase 2) responsible for SEMD Pakistani type. The combination of features observed in the two sisters does not fit with any previously reported SEMD and represents therefore a novel form of autosomal recessive SEMD with MR. Show less