Magdalena I. Tolea

Background: Healthy lifestyles may reduce dementia risk by helping build cognitive reserve across the life course and promoting resilience and better cognitive outcomes in late-life. Whether self-reported lifestyle changes are informative for assessing brain health remains unclear. Objective: To determine whether self-reported lifestyle changes (determinants) are associated with cognition, resilience, and Alzheimer's disease and related dementias (ADRD) biomarkers (outcomes), and whether these associations vary by sociodemographic characteristics and cognitive impairment status. Methods: Data was obtained from 260 adults (age-range: 50–92). Self-reported change (increase/no change, decrease) in diet and physical, cognitive, and social activity from age 25 to present was evaluated in relation to cognition, resilience, and biomarkers within a cross-sectional design. ANCOVA models adjusted for age, sex, race, ethnicity, and education were used to examine associations between lifestyle change and outcomes. Effect modification by sex, race, ethnicity, and cognitive impairment status was also tested. Results: Self-reported increases in physical activity and diet were associated with better cognition and higher resilience, while increases in social activity with higher resilience and larger amygdala volume. Associations were stronger when increases occurred in multiple lifestyle domains. Associations differed by cognitive impairment status; no variation by sex and race was observed. Conclusions: Increases in lifestyle behaviors relative to age 25 were associated with better cognitive and brain health outcomes, especially when increases occurred across multiple domains. These findings align with longitudinal evidence linking lifestyle engagement to cognitive aging and suggest that cross-sectional self-report of change may provide a useful proxy for estimating long-term lifestyle patterns.

Background: Key sociodemographics (e.g., nativity) plausibly related to Alzheimer's disease and related dementia (ADRD) risk have been investigated less frequently in relation to cognitive function, brain imaging, and blood-based biomarkers. Objective: To examine associations between multiple sociodemographics and ADRD/vascular outcomes among middle- to older-age adults. Methods: We used cross-sectional data on 341 Healthy Brain Initiative participants. Outcomes included cognitive domain scores (e.g., episodic memory, language), magnetic resonance imaging (MRI) (e.g., hippocampal and white matter hyperintensity volume), and blood-based biomarkers (e.g., Aβ _42/40 , pTau-217, NfL, GFAP). Sociodemographics included age, sex, racial group, Hispanic ethnicity, primary language, nativity, socioeconomic position, area deprivation, and living alone. Multivariable linear regression examined associations between sociodemographics and brain health outcomes. Results: Mean age was 69 ± 9 and 71% were women. Older individuals, women, Black and Hispanic individuals, those of lower socioeconomic position, and those born outside the US performed worse across various cognitive domains, while those who primarily spoke Spanish (versus English) scored better on episodic memory. Older individuals, women, and Hispanic individuals had worse brain health, and those identifying as other racial group and born outside of the US had better brain health measured via MRI. Older and Hispanic individuals had worse brain health and Black individuals and women had better brain health as measured via blood-based biomarkers. Conclusions: This study contributes to the growing number of studies identifying differences in ADRD/vascular biomarkers by sociodemographics. Additional studies are needed to assess whether social and economic determinants of health are associated with longitudinal change in ADRD/vascular biomarkers.

Background: Declining physical functionality is an indicator of cognitive impairment, distinguishing normal cognition (NC) from dementia. Whether this extends to pre-dementia stages is unclear. Objective: Assess physical performance patterns, evaluate relationships with imaging biomarkers, and identify specific measures distinguishing NC, subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: Group differences (78 NC, 35 SCD, and 41 MCI) in physical function (global function, balance, gait speed, step length, single leg support) were evaluated with logistic regression while distinguishing between MCI due-to-AD and MCI due-to-vascular etiology. Relationships with imaging biomarkers (cortical atrophy score, white matter hyperintensities volumes) were analyzed with ANCOVA. Results: Participants were 68.6 ± 9.3 years old, had 16.2 ± 3.0 years of education, and 23% were ethnoracial minorities. Physical performance distinguished MCI from NC and SCD. Greater performance on the Mini Physical Performance Test (mini PPT) and balance were associated with lower odds of being SCD versus NC (OR _{mini PPT} = 0.73; 95% CI:0.56–0.97; OR _balance = 0.35, 95%CI:0.16–0.80). AD etiology accounted for most group differences in physical performance versus vascular etiology. Consistent associations between biomarkers, physical performance, and cognition were found. Conclusions: Findings suggest that: 1) changes in mini PPT performance and balance may help detect cognitive impairments, as early as the SCD stage; 2) changes in gait speed, gait cycle parameters, and Timed Up-and-Go may indicate more significant cognitive impairment; 3) neuronal loss is linked to subtle changes in physical functionality as early as SCD. Physical performance may be a valuable tool in early dementia detection in clinical settings and could identify targets for early intervention.

This study assessed the feasibility of conducting 3 nonpharmacological interventions with older adults in dementia, exploring the effects of chair yoga (CY), compared to music intervention (MI) and chair-based exercise (CBE) in this population. Using a cluster randomized controlled trial (RCT), 3 community sites were randomly assigned 1:1:1 to CY, MI, or CBE. Participants attended twice-weekly 45-minute sessions for 12 weeks. Thirty-one participants were enrolled; 27 safely completed the interventions and final data collection (retention rate of 87%). Linear mixed modeling was performed to examine baseline and longitudinal group differences. The CY group improved significantly in quality of life compared to the MI group (CY mean = 35.6, standard deviation [SD] = 3.8; MI mean = 29.9, SD = 5.3, P = .010). However, no significant group differences were observed in physical function, behavioral, or psychological symptoms (eg, for mini-PPT: slope _time = 0.01, standard error [SE] = 0.3, P = .984 in the CBE group; slope _time = −0.1, SE = 0.3, P = .869 in the MI group; slope _time = −0.3, SE = 0.3, P = .361 in the CY group) over the 12-week intervention period. Overall, this pilot study is notable as the first cluster RCT of a range of nonpharmacological interventions to examine the feasibility of such interventions in older adults, most with moderate-to-severe dementia. Future clinical trials should be conducted to examine the effects of nonpharmacological interventions for older adults with dementia on health outcomes.

The main goal of our study was to assess the impact of a modified CAIDE risk score on cognitive performance in community-dwelling older adults. The study evaluated a multicultural population consisting of 314 participants enrolled in a cross-sectional aging study with valid measures on cognitive, physical, functional, and emotional health. The CAIDE risk score system was modified to: 1) reflect age and education levels specific to an older adult sample; 2) incorporate self-reported high cholesterol instead of total cholesterol level from blood test; and 3) use the Mini Physical Performance Test (mPPT) as a proxy measure of physical activity (mPPT:=12 active). Using hierarchical linear regression models, ‘risk’ of cognitive impairment (MoCA<26) was assessed based on levels of CAIDE risk score (low, intermediate, high) using the equations reported by the authors of the CAIDE risk score. Higher modified CAIDE risk scores were significantly associated with lower MoCA score (β=-0.447, p<0.001) and with higher Framingham vascular risk scores (r=0.673, p<0.001). The association was robust remaining significant after controlling for significant risk factors (β=-0.424, p=0.015) and followed a dose-response pattern. Likelihood of cognitive impairment increased from 12.1% in the low risk group, to 35.8% in the intermediate, to 65.5% in the high-risk group. Findings suggest the utility of using the modified CAIDE risk score as an indicator of increased risk of cognitive impairment and highlight the need for brief, easy to administer, non-invasive cardiovascular risk batteries to estimate risk of future cognitive decline and dementia in later life.

In vitro and in vivo studies suggest a role for betacellulin in islet neogenesis and regeneration. Since abnormalities in β-cell function play a role in the development of type 2 diabetes, a mutation in the betacellulin gene could potentially contribute to the development of type 2 diabetes. Using RT-PCR, we initially determined that betacellulin was expressed in 9- to 24-week-old human fetal pancreas. We then screened the betacellulin gene for mutations in subjects with type 2 diabetes and identified seven polymorphisms in segments encompassing the 5′ untranslated region (G-233C, A-226G), exon 1 (T̅GC19G̅GC, Cys7Gly), exon 2 (C̅TC130T̅TC, Leu44Phe), exon 4 (T̅TG370A̅TG, Leu124Met), intron 2 (T-31C), and intron 4 (C-4T). These polymorphisms were genotyped in an expanded set of diabetic case and control subjects. Among African Americans (n = 334), the frequency of the Gly7 allele in exon 1 was 31.9% in diabetic case subjects compared with 45.1% in nondiabetic control subjects (P = 0.0004). Allele frequencies for the other polymorphisms did not differ significantly between African-American case and control subjects. Additionally, there were no significant differences in allele frequencies between case and control subjects among the Caucasian sample (n = 426) for any of the seven polymorphisms, including the Gly7 variant. Further studies will be needed to understand the different roles that betacellulin polymorphisms play in susceptibility to type 2 diabetes in Caucasians and African Americans.