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Introduction: This study examined longitudinal associations between self-reported exercise and cognition, with moderation by sex, in individuals with autosomal dominant Alzheimer's disease (ADAD) mutations. We also examined whether changes in exercise over time differed in ADAD mutation carriers versus non-carriers in the years preceding first cognitive symptom onset.
Methods: Participants (n = 491) were ADAD mutation carriers (63%) and non-carriers (37%) from the Dominantly Inherited Alzheimer Network aged 37.6 ± 11.1 years. Participants reported their average time partaking in various leisure-time exercise activities over the past 12 months.
Results: Greater baseline exercise predicted better longitudinal cognitive performance. Sex did not moderate these associations. In the years preceding first cognitive symptoms or last follow-up visit, mutation carriers showed a decline in their exercise engagement compared to mutation non-carriers.
Discussion: Self-reported exercise is associated with preserved cognitive function in those with ADAD mutations; however, AD-related pathways may influence the level of engagement in exercise prior to cognitive symptom onset.
Highlights: Greater weekly exercise predicts slower cognitive decline in ADAD mutation carriers. These associations varied dependent on closeness to estimated symptom onset. These associations were not moderated by sex. Weekly exercise declined in ADAD mutation carriers compared to non-carriers. Results may suggest a bidirectional relationship between exercise and AD risk.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177227 | PMC |
http://dx.doi.org/10.1002/alz.70383 | DOI Listing |
Metabolomics
September 2025
Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire, Angers, France.
Introduction: The definition of Leber's hereditary optic neuropathy (LHON) does not take into account a preclinical phase during which the thickness of retinal nerve fiber layer (RNFL) is increased, prior to optic nerve atrophy, reducing the chances of visual recovery.
Objectives: Search for a metabolomic signature characterizing this preclinical phase and identify biomarkers predicting the risk of LHON onset.
Methods And Results: The blood and tear metabolomic profiles of 90 asymptomatic LHON mutation carriers followed for one year will be explored as a function of RNFL thickness and compared to those of a healthy control.
Ann Clin Transl Neurol
September 2025
Department of Neurology, Brain Centre Utrecht, University Medical Centre Utrecht, Utrecht, the Netherlands.
Objective: We investigated the effects of C9orf72 mutation carriership on peripheral nerve excitability in asymptomatic individuals from families with a history of C9orf72 amyotrophic lateral sclerosis (ALS) and patients.
Methods: We included 47 asymptomatic individuals from families with a history of C9orf72 ALS, of whom 23 were carriers (C9) and 24 were noncarriers (C9). In addition, 11 C9 and 110 C9 ALS patients and 50 healthy controls participated.
Alzheimers Dement
September 2025
Cell Biology Program, Sloan Kettering Institute, New York, New York, USA.
Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.
Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.
Medicine (Baltimore)
September 2025
Diagnosis and Treatment Center for Children, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
Rationale: Phelan-McDermid syndrome, also known as chromosome 22q13.3 deletion syndrome, is a genetic disorder primarily caused by a chromosome 22q13.3 deletion or mutation.
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September 2025
Department of Pediatric Gastroenterology and Hepatology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey.
Unlabelled: The study aimed to evaluate fecal calprotectin levels as indicators of intestinal inflammation in children with cystic fibrosis while examining their relationship with clinical signs, genetic mutations, and therapeutic approaches. Due to the limited number of patients with certain mutation types and the heterogeneity of mutations, patients were grouped accordingly for the analysis of fecal calprotectin levels, in relation to genetic mutation categories. This single-centre study at Istanbul Medical Faculty included 45 cystic fibrosis patients (19 girls, 26 boys) aged 1-18 years and 45 age- and sex-matched healthy controls.
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