Based on the premise that physical activity/exercise impacts hippocampal structure and function, we investigated if hippocampal metabolites for neuronal viability and cell membrane density (i.e., N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)) were higher in older adults performing supervised exercise compared to following national physical activity guidelines. Sixty-three participants (75.3 ± 1.9 years after 3 years of intervention) recruited from the Generation 100 study (NCT01666340_date:08.16.2012) were randomized into a supervised exercise group (SEG) performing twice weekly moderate- to high-intensity training, and a control group (CG) following national physical activity guidelines of ≥ 30-min moderate physical activity ≥ 5 days/week. Hippocampal body and head volumes and NAA, Cho, and Cr levels were acquired at 3T with magnetic resonance imaging and spectroscopic imaging. Sociodemographic data, peak oxygen uptake (VO_2peak), exercise characteristics, psychological health, and cognition were recorded. General linear models were used to assess group differences and associations corrected for age, sex, education, and hippocampal volume. Both groups adhered to their training, where SEG trained at higher intensity. SEG had significantly lower NAA/Cr in hippocampal body than CG (p = 0.04). Across participants, higher training intensity was associated with lower Cho/Cr in hippocampal body (p < 0.001). Change in VO_2peak, increasing VO_2peak from baseline to 3 years, or VO_2peak at 3 years were not associated with hippocampal neurochemicals. Lower NAA/Cr in hippocampal body was associated with poorer psychological health and slightly higher cognitive scores. Thus, following the national physical activity guidelines and not training at the highest intensity level were associated with the best neurochemical profile in the hippocampus at 3 years.

I ntestinal dysbiosis has been linked to metabolic disorders, including insulin resistance and Type 2 Diabetes Mellitus (T2DM). T2DM typically follows a prediabetic stage, during which insulin resistance develops. During early stages of T2DM, its development can be corrected, thus potentially preventing or delaying the onset of the disease. This study aimed to compare the gut microbiome of individuals with elevated fasting blood glucose to that of individuals with glucose levels within the normal range. This study involved 65 older adults (ages 76–83 years) enrolled from the randomized controlled trial entitled the “Generation 100 Study”, all of whom consented to provide their gut microbiome samples. We employed a high-throughput sequencing of the bacterial 16S rRNA gene to obtain metagenomic microbial profiles for all participants. These profiles were then correlated with clinical measures. Overall, microbial alpha diversity was significantly reduced in the high glucose group. We have also observed distinct patterns of microbial beta diversity between high and normal glucose groups. At the phylum level, we found that Synergistes, Elusimicobia, Euryarchaeota, Verrucomicrobia, and Proteobacteria were all significantly decreased in participants with high blood glucose. Additionally, P. copri (ASV 909561) was significantly elevated (10-fold increase) in the high glucose groups, suggesting that it may serve as an early T2DM marker. In contrast to prior reports on the Fusobacterium genus, we found that it was significantly increased in the normal glucose group, with a significant 151-fold increase compared to the high glucose group. Our results indicate significant changes in the microbiome that may provide valuable insights for early intervention in pre-diabetic states.

Intestinal dysbiosis has been linked to metabolic disorders, including insulin resistance and type 2 diabetes mellitus (T2DM). T2DM typically follows a prediabetic stage, during which insulin resistance develops. During the early stages of T2DM, its development can be corrected, thus potentially preventing or delaying the onset of the disease. This secondary, exploratory, cross-sectional comparison study aimed to contrast the gut microbiome of individuals with elevated fasting blood glucose to that of individuals with glucose levels within the normal range. This study involved 65 older adults (ages 76–83 years) enrolled from the randomized controlled trial entitled the “Generation 100 Study”, all of whom consented to provide their gut microbiome samples. We employed a high-throughput sequencing of the bacterial 16S rRNA gene to obtain metagenomic microbial profiles for all participants. These profiles were then correlated with clinical measures. Overall, microbial alpha diversity was significantly reduced in the high glucose group. We have also observed distinct patterns of microbial beta diversity between high and normal glucose groups. At the phylum level, we found that Synergistes, Elusimicobia, Euryarchaeota, Verrucomicrobia, and Proteobacteria were all significantly decreased in participants with high blood glucose. Additionally, P. copri (ASV 909561) was significantly elevated (10-fold increase) in the high glucose groups, suggesting that it may serve as an early T2DM marker. In contrast to prior reports on the Fusobacterium genus, we found that it was significantly increased in the normal glucose group, with a significant 151-fold increase compared to the high glucose group. Directly linking gut microbiota profiles with clinical indicators such as fasting blood glucose and T2DM diagnosis allows the identification of specific microbial features associated with glucose dysregulation, providing preliminary population-level evidence to guide future translational research. Our results indicate significant changes in the microbiome that may provide valuable insights for early intervention in pre-diabetic states.

Background: Interventions promoting increased physical activity (PA) and limited sedentary time in older adults are urgently required. This study examines how 5 years of supervised high-intensity interval training (HIIT), or moderate-intensity continuous training (MICT) affects PA and sedentary time measured objectively, during, and 5 years after the intervention, compared to an unsupervised control group. Methods: In total, 1405 participants with a mean age of 72.8 years, consisting of 51% females, were randomized 1:1:2 to 5 years of 2 weekly sessions of HIIT (90% of peak heart rate), MICT (70% of peak heart rate), or as controls asked to follow national PA recommendations. Total PA, number of steps, sedentary time, light PA, moderate PA, and vigorous PA were measured with ActiGraph GT3X+ monitors at baseline, years 1, 3, 5, and 10. Results: There were no significant between-group differences throughout the study. However, HIIT, MICT, and control demonstrated significant changes after 1 year, including decreased total PA (−10%, −9%, and −9%, respectively), increased sedentary time (164, 163, and 163 min/d, respectively), and increased moderate PA (21, 21, and 19 min/d, respectively). Furthermore, after 10 years, pooled moderate to vigorous PA was maintained or increased in all groups (5.7, 1.9, and 1.5 min/d in HIIT, MICT, and control, respectively). Conclusion: HIIT, MICT, and control exhibited a similar long-term effect on objective PA and sedentary time in a general population of older adults. Notably, both supervised and unsupervised exercise combined with regular follow-up hindered the expected age-related decline in moderate to vigorous PA over 10 years.

In aging, white matter hyperintensities (WMH) or white matter signal aberrations (WMSA), a proxy for cerebral small vessel disease, are the most common age‐related finding on brain MRI scans, with women reported to have a greater burden. Previous studies found that WMH/WMSA were linked to lower cortical volume and thickness. However, no study has investigated the connection between WMSA and both cortical thickness and area using multiple assessments over 9 years. We hypothesized that increasing WMSA was associated with a decrease in both cortical thickness and area over time, compounding the age‐typical decrease, and that the effect was more pronounced in women than men. Our cohort consisted of 104 older adults from the general population, born between 1936 and 1942, scanned at the same 3T scanner at baseline (mean age 72.4 years), and followed up at 1‐, 3‐, 5, and 9 years. We analyzed the 3D MPRAGE scans in FreeSurfer's longitudinal pipeline and extracted the volume of WMSA, cortical thickness and area, grey matter‐white matter intensity ratio, plus hippocampal and intracranial volume. Linear mixed‐effects models included the interaction between sex and WMSA on cortical thickness and area, and hippocampal volume. We also performed sex‐specific analyses. Finally, complete case and sensitivity analyses with known confounders were run. In both men and women, baseline WMSA volume was 3.6 cm ³ (95% CI, 2.1–6.2), followed by an average annual growth rate of 7.2% (95% CI, 6.1–8.3). Increasing WMSA over time was associated with accelerated cortical thinning. In men, the association between WMSA and cortical thinning was more pronounced and present in more lobes than in women, despite similar WMSA volume and growth in both sexes. In the lobes with accelerated cortical thinning, increasing WMSA was also associated with an increase in cortical area present only in men. The sex‐specific analyses revealed even more pronounced differences in the relationships between WMSA growth and cortical features over time. The changes in cortex associated with WMSA volume were superimposed on the changes related to aging in both sexes. Change in WMSA over time was not directly associated with change in hippocampal volume. Complete case and sensitivity analyses supported the main findings. Thus, contrary to our hypothesis, WMSA change over 9 years was connected to greater cortical thinning alongside a surprising increase in cortical area in men, despite men and women having similar WMSA volume and growth. Our results underscore the presence of marked sex differences in cortical plasticity in the aging brain in the presence of WMSA. WMSA, the most common age‐related proxy for small vessel disease, contributed significantly and above that related to aging, to cortical changes, more so in men than women.

The lasting effects of exercise on brain health in older adults are poorly documented. The aim of this study was to assess the long-term, post-intervention effects 4 years after a 5-year exercise intervention on brain volumes and cognitive abilities in older adults. A total of 106 older adults (70-77 years at baseline) from the randomized controlled trial (RCT) Generation 100 study randomized into high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), or a control group following national physical activity guidelines for 5 years were included. Post-intervention assessment was performed 9 years after inclusion. Brain magnetic resonance imaging (MRI) and exercise characteristics were acquired at baseline and after 1, 3, 5, and 9 years. Cognitive abilities were assessed with verbal list learning, pattern separation, and odor identification tests at baseline and 9 years. Linear mixed models were used to examine the interaction between exercise group and time on brain volumes. The analyses were repeated, including self-reported exercise behaviors (intensity and duration) as covariates. To examine the general effect of exercise intensity independent of group, a separate model was run across all participants with self-reported exercise intensity as independent variable. For cognition, linear regressions examined associations between exercise group and self-reported exercise intensity on cognitive scores at 9 years, and hippocampal volume loss over time on cognitive scores at 9 years. Whether baseline peak oxygen uptake (VO_2peak) predicted brain volumes and cognitive scores at 9 years was tested with linear regression. The time × group interaction revealed greater hippocampal volume loss in the HIIT compared with the control group 4 years after the intervention ended, similar to what was found during the intervention. We did not find that self-reported exercise behavior was associated with hippocampal volume over time. Across all participants, greater hippocampal volume loss was associated with poorer verbal memory at 9 years. The test scores on verbal memory and pattern separation did, however, not differ between the groups, but the MICT, and trending for the HIIT group, had higher odor identification scores at 9 years. Higher baseline VO_2peak predicted larger cortical volume and better pattern separation score at 9 years across intervention groups, in line with what was observed during the intervention. The control group, which followed the national physical activity guidelines, had the lowest hippocampal volume loss over time, even 4 years after the end of a 5-year exercise intervention in fit older adults. Furthermore, higher baseline VO_2peak provided protective effects on both cortical volume and pattern separation ability across almost a decade, independent of exercise group. ClinicalTrials.gov NCT01666340 (registered 16 August 2012).