Search

Background: Alzheimer's disease is caused by modifiable and non-modifiable risk factors. Randomised controlled trials have investigated whether the strongest genetic risk factor for Alzheimer's disease, APOE4, impacts the effectiveness of exercise on health. Systematic reviews are yet to evaluate the effect of exercise on physical and cognitive outcomes in APOE genotyped participants. A quality assessment of these randomised controlled trials is needed to understand the impact genotype has on the potential success of intervention. This systematic review aimed to determine if the APOE4 genotype influences the effectiveness of exercise-based randomised controlled trials. Method: Searches on MEDLINE, EMBASE, and PsycINFO identified eligible exercise based randomised controlled trials incorporating participants with varied cognitive abilities. Quality assessments were conducted. Results: Nineteen studies met the inclusion criteria for systematic review, and 3 for the meta-analysis. Very low to moderate quality evidence showed that APOE4 carriers benefitted more than APOE4 non-carriers on cognitive (e.g. executive function, learning) and physical (e.g. relative telomere length) outcomes after exercise; and that APOE4 non-carriers benefited over carriers for physical (serum BDNF, gait speed) and cognitive (global cognition, verbal memory) markers. Very low quality evidence indicated that there was no evidence of difference between APOE4 carriers and non-carriers on physical function outcomes in meta-analysis. Several areas of study design and reporting, including maintenance of relative exercise intensity and complete statistical reporting, were identified as needing improvement. Discussion: This systematic review found very limited evidence to suggest that exercise interventions can benefit APOE4 carriers and non-carriers equally, though conclusions were limited by evidence quality. Further randomised controlled trials, stratifying participants by APOE status are required to better understand the relationship between APOE genotype and the effect of exercise on health-related outcomes. Trial registration: This review was registered with PROSPERO (CRD42023436842). Registered on June 16, 2023. [ABSTRACT FROM AUTHOR]

Background: Modifiable (physical activity) and non-modifiable (sex and genotype) risk factors interact to affect Alzheimer's disease (AD) risk. Further investigation is necessary to understand if these factors influence brain volume and cognition. Objective: The study aimed to assess the effect of physical activity, APOE genotype, and sex on AD risk, brain volume, and cognition. Methods: UK Biobank data from 2006 to 2023 was accessed. Physical activity was measured by accelerometers, and International Physical Activity Questionnaire. Outcomes were AD incidence; brain volume (ventricular cerebrospinal fluid and total brain); and cognition (executive function, memory, visuospatial ability, processing speed, and reaction time). Logistic and linear regression models were conducted. Results: 69,060 participants met inclusion criteria (mean age: 62.28 years, SD: 7.84; 54.64% female). Higher self-reported (OR = 0.63, 95% CI [0.40, 1.00], p = 0.047) and accelerometer-assessed (OR = 0.96 [0.93, 0.98], p = 0.002) physical activity was associated with lower disease incidence. Smaller ventricular cerebrospinal fluid volume (β= – 65.43 [– 109.68, – 17.40], p = 0.007), and larger total brain volume (β= 4398.46 [165.11, 8631.82], p < 0.001) was associated with increased accelerometer-assessed and self-reported physical activity respectively. Both brain volume analyses were moderated by sex. Increased accelerometer-assessed physical activity levels were associated with faster reaction time (β= – 0.43 [– 0.68, – 0.18], p = 0.001); though poorer visuospatial ability (β= – 0.06 [– 0.09, – 0.03], p < 0.001), and executive function (β= 0.49 [0.31, 0.66], p < 0.001; β= 0.27 [0.10, 0.45], p = 0.002) was related to self-reported physical activity levels. Conclusions: Higher levels of physical activity reduce AD risk independently of non-modifiable risk factors. Moderation of sex on brain volume highlighted the importance of incorporating non-modifiable risk factors in analysis. [ABSTRACT FROM AUTHOR]

CD34+ progenitor cells with angiogenic capabilities traffic into blood during exercise and extravasate afterwards but the magnitude of this response varies between people. We examined whether exercise‐induced progenitor cell trafficking is influenced by cardiorespiratory fitness (maximum oxygen uptake; V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$). Ten males (age: 23 ± 3 years; V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$: 61.88 ± 4.68 mL kg min−1) undertook 1 h of treadmill running at 80% of V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$. Blood samples were collected before exercise (Pre), in the final minute of exercise (0 h) and afterwards at 0.25, 1 and 24 h. Pan‐progenitor cells (CD34+, CD34+CD45dim) and putative endothelial progenitor cells (CD34+CD133+, CD34+VEGFR2+, CD34+CD45dimVEGFR2+) were quantified using flow cytometry. Progenitor subpopulations (except for CD34+CD45dimVEGFR2+) increased at 0 h (P < 0.05) and returned to pre‐exercise levels by 1 h. V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ was positively associated with the exercise‐induced progenitor cell response and there were statistically significant time × V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ interactions for CD34+, CD34+CD45dim and CD34+CD133+ subpopulations but not VEGFR2‐expressing progenitor cells. There were statistically significant correlations between V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ and ingress (r > 0.70, P < 0.025) and egress (r > −0.77, P < 0.009) of progenitor cell subsets (CD34+, CD34+CD45dim, CD34+CD133+), showing that cardiorespiratory fitness influences the magnitude of progenitor cell mobilisation into the blood and subsequent extravasation. These data may provide a link between high levels of cardiorespiratory fitness and vascular health. [ABSTRACT FROM AUTHOR]

Plasma amino acid levels were measured in autistic (n=12), Asperger syndrome (n=11) patients, their parents and siblings. Patients with autism or Asperger syndrome and their siblings and parents all had raised glutamic acid, phenyalanine, asparagine, tyrosine, alanine, and lysine levels than age-matched controls. Results suggest dysregulated amino acid metabolism as an underlying biochemical basis. (Contains references.) (Author/DB)