Financial exploitation vulnerability in aging is a growing public health concern, yet its neural correlates remain poorly understood. Although psychosocial and cognitive factors confer risk, emerging evidence suggests that regional differences in brain structure may also contribute to vulnerability before overt cognitive impairment. In this study, 128 cognitively unimpaired older adults (ages 51 to 87 years, 76% female) completed structural magnetic resonance imaging and the Perceived Financial Vulnerability Scale, a self-report measure of financial exploitation risk. We examined age-stratified associations between perceived financial exploitation vulnerability and gray matter volume in relatively younger (n = 67) and older (n = 61) participants. Whole-brain voxel-based morphometry analyses revealed that higher perceived financial exploitation vulnerability was associated with lower gray matter volume in the right amygdala/anterior hippocampus (max t = 4.55, pFWE = 0.029) and left precuneus (max t = 5.40, pFWE = 0.031) among older participants, but not younger participants. In post hoc exploratory analyses modeling age as a continuous variable across the full sample, the age × perceived financial exploitation vulnerability interaction was significant for gray matter volume in the left precuneus and was observed at a trend level in the right amygdala/anterior hippocampus, with more negative associations at older ages. These cross-sectional findings identify regional gray matter correlates of perceived financial exploitation vulnerability that may vary across later adulthood.
Age is a major determinant of demyelination and remyelination capacity. Here, we investigated age-dependent brain responses to acute cuprizone exposure in female C57BL/6 mice using longitudinal multimodal Magnetic resonance imaging (MRI) and histological analyses. Our aim was to determine whether any brain region in very old animals remains susceptible to cuprizone-induced pathology. Adult (6-month-old) and aged (18-month-old) mice received 0.2% cuprizone in the diet for 5 weeks, followed by 4 weeks of recovery on normal chow, with in vivo MRI performed at baseline, during intoxication, and throughout recovery. Magnetization transfer ratio (MTR) and T2-weighted signal were used as MRI surrogates of myelin integrity and neuroinflammation, respectively, whereas T1-weighted signal was assessed as a potential marker sensitive to oxidative stress. In adult mice, cuprizone induced robust and region-specific pathology, including reduced MTR and increased T2-weighted signal in the corpus callosum, accompanied by microgliosis, astrocytosis, and increased APP-positive dystrophic neurites. These abnormalities showed only partial recovery following cuprizone withdrawal. In contrast, cuprizone elicited little or no detectable change in these forebrain white-matter regions and in other brain areas in aged mice. However, the cerebellar nuclei remained susceptible at both ages, exhibiting persistent MTR decreases and T2-weighted signal increases, corroborated by histological evidence of demyelination and gliosis. T1-weighted signal increased broadly in adult, but not in aged, mice during intoxication, consistent with cuprizone-associated oxidative stress. Together, these findings demonstrate pronounced age- and region-dependent effects of cuprizone and identify the cerebellar nuclei as a sensitive target of demyelination across the lifespan. Moreover, the non-invasive nature of MRI enables efficient assessment of regional differences over time.
Background Aerobic exercise that improves cardiorespiratory fitness (CRF) may induce hippocampal changes that help counteract age-related memory decline. The Umeå HIT Study, a randomized controlled trial, examined three months of controlled high-intensity interval training (HIT) and moderate-intensity training (MIT) in older adults. Here, we tested whether increases in CRF (VO₂peak), regardless of training modality, predicted changes in episodic-memory pattern completion and hippocampal structure and function (CA4/DG, CA2/3, CA1). Method Forty-two older adults (66–79 years, 45% males) not engaged in regular physical exercise participated in 3 months of twice-weekly supramaximal HIT (20 min including 10 × 6-s intervals) or aerobic MIT (40 min including 3 × 8-m intervals). Before and after the exercise interventions, the participants underwent magnetic resonance imaging (MRI) of the hippocampus, including an episodic memory pattern completion task with concomitant functional MRI. Results Exercise-induced change in VO2peak (M = 1.5 mL/kg/min, 95% CI[0.8; 2.3]) after three months aerobic exercise of HIT or MIT did not predict change in pattern completion (F(1,33) = 0.02, B = −0.061 p = .883, r2 = 0.001). However, change in VO2peak predicted BOLD signal change in the left hippocampal subfield CA4/DG (F(1,33) = 4.56, B = 0.06 p = .04, r2 = 0.12), which in turn, predicted change in pattern completion (F(1,34) = 5.19, B = 0.026, p = .029, r2 = 0.13). Conclusion Three months of high- or moderate-intensity training which improves CRF may lead to hippocampal functional changes that, in turn, are linked to enhanced episodic memory pattern completion.
Background Health-related factors may influence blood-based biomarkers (BBBM) of Alzheimer's disease (AD). In this analysis, associations between modifiable factors and plasma biomarkers of neurodegeneration were investigated across the Alzheimer's disease spectrum and in cognitively healthy controls in a cerebrospinal fluid–confirmed (CSF) cohort. Methods Plasma biomarkers included the Aβ1–42/1–40 ratio, pTau181, GFAP, NFL and ApoE4. Multiple linear regression was used to test associations with lifestyle factors (physical activity and sleep), physiological factors (including renal and lipid metabolism markers), genetic factors (APOE ε4), age and sex. Percentage effect sizes and confidence intervals were calculated. Results The study included CSF-characterized individuals with AD (mild cognitive impairment due to AD and AD dementia) and cognitively healthy controls (n = 116; mean age 71.2 years). Overall, the associations were modest, with wide confidence intervals reflecting variability in the outcomes and the limited range of predictors in this relatively healthy sample. In CSF-confirmed participants, age emerged as the most consistent predictor of plasma biomarker levels, particularly NFL and pTau181. APOE ε3/ε4 genotype was additionally associated with higher pTau181 levels. Other demographic, metabolic and lifestyle-related variables showed only weak or inconsistent associations. Conclusion To implement BBBM in broader populations, a systematic evaluation of confounders is required. As aging cohorts present with mixed pathologies, strategies to address heterogeneity will be essential. The limited number of robust associations observed suggests that plasma biomarkers are influenced primarily by age and genetic background rather than by metabolic factors in this cohort. Validation in more diverse populations remains warranted.
Our aim was to investigate the change in brain glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) in amyloid beta positive and negative amnestic mild cognitive impairment (aMCI) patients. We investigated associations between change in [18F]FDG uptake and cognitive functioning in aMCI patients over up to 3 years. Twenty patients underwent [18F]FDG PET (15 men and 5 women, mean age 73.0 years, SD 6.3 at baseline) within a short time interval from [18F]Flutemetamol PET. The patients were classified as amyloid positive vs. negative based on the amyloid PET marker [18F]Flutemetamol uptake. Patients were examined with brain MRI and cognitive tests at baseline and after 3-year follow-up or earlier if the patient had converted to probable Alzheimer's disease. [18F]FDG data was analysed with automated region-of-interest analysis and voxel-based statistical parametric mapping (SPM). [18F]FDG uptake nor change of [18F]FDG uptake over time differed between amyloid positive and negative groups. However, the amyloid positive patients exhibited significant decline in MMSE scores over three years while the amyloid negative patients maintained stable MMSE level over time. The amyloid positive group had poorer episodic memory scores at baseline and follow-up, and significantly slower processing speed at follow-up as well as significantly more negative change over time in language functions compared to amyloid negative patients. Moreover, we found that [18F]FDG uptake was positively associated with cognition in the whole aMCI patient group. Together, our results suggest that brain glucose metabolism in aMCI is independent of amyloid pathology, and probably reflects other brain degenerative processes.
