Nondemented Adults Research Articles

Alzheimer's Disease and Small Vessel Disease Differentially Affect White Matter Microstructure.

Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults. Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid β1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract. AD pathology, APOE-ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect. Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.

Association of Plasma Amyloid-β and Dementia Among Black and White Older Adults.

Plasma amyloid-β (Aβ) has emerged as an important tool to detect risks of Alzheimer's disease and related dementias, although research in diverse populations is lacking. We compared plasma Aβ42/40 by race with dementia risk over 15 years among Black and White older adults. In a prospective cohort of 997 dementia-free participants (mean age 74±2.9 years, 55% women, 54% Black), incident dementia was identified based on hospital records, medication, and neurocognitive test over 15 years. Plasma Aβ42/40 was measured at Year 2 and categorized into low, medium, and high tertile. We used linear regression to estimate mean Aβ42/40 by race and race-stratified Cox proportional hazards models to assess the association between Aβ42/40 tertile and dementia risk. Black participants had a lower age-adjusted mean Aβ 42/40 compared to White participants, primarily among APOE ɛ4 non-carriers (Black: 0.176, White: 0.185, p = 0.035). Among Black participants, lower Aβ 42/40 was associated with increased dementia risk: 33% in low (hazard ratios [HR] = 1.77, 95% confidence interval 1.09-2.88) and 27% in medium tertile (HR = 1.67, 1.01-2.78) compared with 18% in high Aβ 42/40 tertile; Increased risks were attenuated among White participants: 21% in low (HR = 1.43, 0.81-2.53) and 23% in medium tertile (HR = 1.27, 0.68-2.36) compared with 15% in high Aβ 42/40 tertile. The interaction by race was not statistically significant. Among community-dwelling, non-demented older adults, especially APOE ɛ4 non-carriers, Black individuals had lower plasma Aβ 42/40 and demonstrated a higher dementia risk with low Aβ42/40 compared with White individuals.

Cerebrospinal fluid α-synuclein adds the risk of cognitive decline and is associated with tau pathology among non-demented older adults

BackgroundThe role of α-synuclein in dementia has been recognized, yet its exact influence on cognitive decline in non-demented older adults is still not fully understood.MethodsA total of 331 non-demented individuals were included in the study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants were divided into two distinct groups based on their α-synuclein levels: one with lower levels (α-synuclein-L) and another with higher levels (α-synuclein-H). Measurements included neuropsychiatric scales, cerebrospinal fluid (CSF) biomarkers, and blood transcriptomics. The linear mixed-effects model investigated the longitudinal changes in cognition. Kaplan-Meier survival analysis and the Cox proportional hazards model were utilized to evaluate the effects of different levels of α-synuclein on dementia. Gene set enrichment analysis (GSEA) was utilized to investigate the biological pathways related to cognitive impairment. Pearson correlation, multiple linear regression models, and mediation analysis were employed to investigate the relationship between α-synuclein and neurodegenerative biomarkers, and their potential mechanisms affecting cognition.ResultsHigher CSF α-synuclein levels were associated with increased risk of cognitive decline and progression to dementia. Enrichment analysis highlighted the activation of tau-associated and immune response pathways in the α-synuclein-H group. Further correlation and regression analysis indicated that the CSF α-synuclein levels were positively correlated with CSF total tau (t-tau), phosphorylated tau (p-tau) 181, tumor necrosis factor receptor 1 (TNFR1) and intercellular cell adhesion molecule-1 (ICAM-1). Mediation analysis further elucidated that the detrimental effects of CSF α-synuclein on cognition were primarily mediated through CSF t-tau and p-tau. Additionally, it was observed that CSF α-synuclein influenced CSF t-tau and p-tau181 levels via inflammatory pathways involving CSF TNFR1 and ICAM-1.ConclusionsThese findings elucidate a significant connection between elevated levels of CSF α-synuclein and the progression of cognitive decline, highlighting the critical roles of activated inflammatory pathways and tau pathology in this association. They underscore the importance of monitoring CSF α-synuclein levels as a promising biomarker for identifying individuals at increased risk of cognitive deterioration and developing dementia.

Dose-response associations between physical activity and sedentary time with functional disability in older adults with or without frailty: a prospective cohort study.

Evidence regarding the dose-response curve shapes of physical activity (PA) and sedentary time (ST) in older adults with functional disability (FD) is extremely limited. Moreover, these associations may differ depending on with/without frailty. We examined the dose-response associations between moderate-to-vigorous PA (MVPA) and ST with FD among older adults with/without frailty. We included 7,480 initially nondisabled adults (3,795 men and 3,685 women) aged 65-84 years in Ota City, Tokyo, Japan. MVPA and ST were evaluated using the International Physical Activity Questionnaire-Short Form. FD was prospectively identified using a nationally unified database of the long-term care insurance system. Frailty was determined using Check-List 15, validated against Fried's frailty criteria. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and ST for FD were calculated, and dose-response curves were examined using restricted cubic splines. During 3.6 years of follow-up, 1,001 (13.4%) participants had FD. Among all participants, compared with no MVPA, the HRs for FD reduced linearly up to approximately 2000 metabolic equivalents (METs)■min/week of MVPA, and the lowest HR (HR: 0.61, 95% CI: 0.51-0.74) was reached at around 3,000-4,000 METs■min/week. Although the shape of this association was consistent regardless of with/without frailty, the magnitude of the association tended to be stronger in frail older adults than in non-frail older adults. Compared with those for the median (300 min/day) of ST, the HRs for FD increased linearly as ST reached approximately 600 min/day or more, independent of MVPA, with a maximum HR of 1.31 (95% CI: 1.01-1.71) for 1,080 min/day among all participants. This association was more pronounced among non-frail older adults but not statistically significant among frail older adults. Higher MVPA levels consistently reduced the incidence of FD regardless of frailty in a significant inverse nonlinear dose-response manner. A significant positive nonlinear dose-response association between ST and FD risk was identified among non-frail older adults but not among frail older adults. Increasing MVPA and reducing prolonged ST are important for preventing FD among non-frail older adults. However, reducing ST alone may be insufficient; increasing MVPA, even if by only small increments, is highly recommended for frail older adults.

Can telehealth expansion boost health care utilization specifically for patients with substance use disorders relative to patients with other types of chronic disease?

Patients with substance use disorders (SUDs) exhibit low healthcare utilization despite high risk of poor outcomes. Telehealth expansion may boost utilization, but it is unclear whether telehealth can increase utilization for patients with SUDs beyond that expected for other chronic diseases amenable to remote treatment, like type 2 diabetes. This information is needed by health systems striving to improve SUD outcomes, specifically. This study compared the impact of telehealth expansion during the COVID-19 public health emergency (PHE) on utilization for patients with SUDs and diabetes. Using Wisconsin Medicaid administrative, enrollment and claims data 12/1/2018-12/31/2020, this cohort study included nonpregnant, nondisabled adults 19-64 years with SUDs (N = 17,336) or diabetes (N = 8,499). Outcomes included having a primary care visit in the week (any, and telehealth) for any diagnosis, or a SUD or diabetes diagnosis; and the weekly fraction of visits completed by telehealth. Logistic and fractional regression examined outcomes pre- and post-PHE. Covariates included age, sex, race, ethnicity, income, geography, and comorbid medical and psychotic disorders. Post-PHE, patients with SUDs exhibited greater likelihood of telehealth utilization (percentage point difference (PPD) per person-week: 0.2; 95% CI: 0.001-0.003; p<0.001) and greater fractional telehealth use (PPD: 1.8; 95%CI: 0.002-0.033; p = 0.025) than patients with diabetes despite a larger overall drop in visits (PPD: -0.5; 95%CI: -0.007- -0.003; p<0.001). Following telehealth expansion, patients with SUDs exhibited greater likelihood of telehealth utilization than patients with diabetes. This advantage lessened the substantial PHE-induced healthcare disruption experienced by patients with SUDs. Telehealth may boost utilization for patients with SUDs.

Amyloid pathology mediates the associations between plasma fibrinogen and cognition in non-demented adults.

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aβ42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aβ42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aβ42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aβ pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aβ pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aβ pathology. Fibrinogen was associated with both cognition and Aβ pathology. Aβ pathology may be a critical mediator for impacts of fibrinogen on cognition.

ANU-ADRI scores, tau pathology, and cognition in non-demented adults: the CABLE study

BackgroundIt has been reported that the risk of Alzheimer’s disease (AD) could be predicted by the Australian National University Alzheimer Disease Risk Index (ANU-ADRI) scores. However, among non-demented Chinese adults, the correlations of ANU-ADRI scores with cerebrospinal fluid (CSF) core biomarkers and cognition remain unclear.MethodsIndividuals from the Chinese Alzheimer’s Biomarker and LifestyLE (CABLE) study were grouped into three groups (low/intermediate/high risk groups) based on their ANU-ADRI scores. The multiple linear regression models were conducted to investigate the correlations of ANU-ADRI scores with several biomarkers of AD pathology. Mediation model and structural equation model (SEM) were conducted to investigate the mediators of the correlation between ANU-ADRI scores and cognition.ResultsA total of 1078 non-demented elders were included in our study, with a mean age of 62.58 (standard deviation [SD] 10.06) years as well as a female proportion of 44.16% (n = 476). ANU-ADRI scores were found to be significantly related with MMSE (β = -0.264, P < 0.001) and MoCA (β = -0.393, P < 0.001), as well as CSF t-tau (β = 0.236, P < 0.001), p-tau (β = 0.183, P < 0.001), and t-tau/Aβ42 (β = 0.094, P = 0.005). Mediation analyses indicated that the relationships of ANU-ADRI scores with cognitive scores were mediated by CSF t-tau or p-tau (mediating proportions ranging from 4.45% to 10.50%). SEM did not reveal that ANU-ADRI scores affected cognition by tau-related pathology and level of CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2).ConclusionANU-ADRI scores were associated with cognition and tau pathology. We also revealed a potential pathological mechanism underlying the impact of ANU-ADRI scores on cognition.

Salience Network Functional Connectivity Mediates Association Between Social Engagement and Cognition in Non-Demented Older Adults: Exploratory Investigation.

Social engagement has beneficial effects during cognitive aging. Large-scale cognitive brain network functions are implicated in both social behaviors and cognition. We evaluated associations between functional connectivity (FC) of large-scale brain cognitive networks and social engagement, characterized by self-reported social network size and contact frequency. We subsequently tested large-scale brain network FC as a potential mediator of the beneficial relationship between social engagement and cognitive performance. 112 older adults (70.7±7.3 years, range 54.6-89.7; 84 women) completed the Lubben Social Network Scale 6 (LSNS-6), National Alzheimer's Coordinating Center (NACC) Uniform Data Set 3 (UDS-3) cognitive battery, and resting state fMRI. We completed seed-based correlational analysis in the default mode and salience networks. Significant associations between social engagement scores and cognitive performance, as well as between social engagement and FC of brain networks, informed the construction of mediation models. Social engagement was significantly associated with executive function and global cognition, with greater social engagement associated with better cognitive performance. Social engagement was significantly associated with salience network FC, with greater social engagement associated with higher connectivity. Salience network FC partially mediated associations between social engagement and both executive function and global cognition. Our results suggest that the salience network is a key mediator of the beneficial relationship between social engagement and cognition in older adults.

How Does Telehealth Expansion Change Access to Healthcare for Patients With Different Types of Substance Use Disorders?

Patients with substance use disorders (SUDs) exhibit low healthcare utilization despite high medical need. Telehealth could boost utilization, but variation in uptake across SUDs is unknown. Using Wisconsin Medicaid enrollment and claims data from December 1, 2018, to December 31, 2020, we conducted a cohort study of telemedicine uptake in the all-ambulatory and the primary care setting during telehealth expansion following the COVID-19 public health emergency (PHE) onset (March 14, 2020). The sample included continuously enrolled (19 months), nonpregnant, nondisabled adults aged 19 to 64 years with opioid (OUD), alcohol (AUD), stimulant (StimUD), or cannabis (CannUD) use disorder or polysubstance use (PSU). Outcomes: total and telehealth visits in the week, and fraction of visits in the week completed by telehealth. Linear and fractional regression estimated changes in in-person and telemedicine utilization. We used regression coefficients to calculate the change in telemedicine utilization, the proportion of in-person decline offset by telemedicine uptake ("offset"), and the share of visits completed by telemedicine ("share"). The cohort (n = 16 756) included individuals with OUD (34.8%), AUD (30.1%), StimUD (9.5%), CannUD (9.5%), and PSU (19.7%). Total and telemedicine utilization varied by group post-PHE. All-ambulatory: total visits dropped for all, then rose above baseline for OUD, PSU, and AUD. Telehealth expansion was associated with visit increases: OUD: 0.489, P < .001; PSU: 0.341, P < .001; StimUD: 0.160, P < .001; AUD: 0.132, P < .001; CannUD: 0.115, P < .001. StimUD exhibited the greatest telemedicine share. Primary care: total visits dropped for all, then recovered for OUD and CannUD. Telemedicine visits rose most for PSU: 0.021, P < .001; OUD: 0.019, P < .001; CannUD: 0.011, P < .001; AUD: 0.010, P < .001; StimUD: 0.009, P < .001. PSU and OUD exhibited the greatest telemedicine share, while StimUD exhibited the lowest. Telemedicine fully offset declines for OUD only. Telehealth expansion helped maintain utilization for OUD and PSU; StimUD and CannUD showed less responsiveness. Telehealth expansion could widen gaps in utilization by SUD type.

Neuropsychological correlates of early grief in bereaved older adults.

Prolonged grief disorder (PGD) is associated with impairments in cognitive functioning, but the neuropsychological correlates of early grief in older adults are poorly understood. This preliminary study cross-sectionally examined neuropsychological functioning in bereaved adults with high and low grief symptoms and a non-bereaved comparison sample and further explored the relationship between multidomain cognitive measures and grief severity. A total of ninety-three nondemented older adults (high grief: n = 44; low grief: n = 49) within 12 months post-bereavement and non-bereaved comparison participants (n = 43) completed neuropsychological battery including global and multiple domain-specific cognitive functioning. Linear regression models were used to analyze differences in multidomain cognitive measures between the groups and specifically examine the associations between cognitive performance and grief severity in the bereaved, after covariate adjustment, including depressive symptoms. Bereaved older adults with higher grief symptoms performed worse than those with lower symptoms and non-bereaved participants on executive functioning and attention and processing speed measures. In the bereaved, poorer executive functioning, attention and processing speed correlated with higher grief severity. Attention/processing speed-grief severity correlation was seen in those with time since loss ≤ 6 months, but not > 6 months. Intense early grief is characterised by poorer executive functioning, attention, and processing speed, resembling findings in PGD. The putative role of poorer cognitive functioning during early grief on the transition to integrated grief or the development of PGD remains to be elucidated.

Does the Cognitive Change Index Predict Future Cognitive and Clinical Decline? Longitudinal Analysis in a Demographically Diverse Cohort.

The Cognitive Change Index (CCI) is a widely-used measure of self-perceived cognitive ability and change. Unfortunately, it is unclear if the CCI predicts future cognitive and clinical decline. We evaluated baseline CCI to predict transition from normal cognition to cognitive impairment in nondemented older adults and in predementia groups including, subjective cognitive decline, motoric cognitive risk syndrome, and mild cognitive impairment. Different versions of the CCI were assessed to uncover any differential risk sensitivity. We also examined the effect of ethnicity/race on CCI. Einstein Aging Study participants (N = 322, Mage = 77.57±4.96, % female=67.1, Meducation = 15.06±3.54, % non-Hispanic white = 46.3) completed an expanded 40-item CCI version (CCI-40) and neuropsychological evaluation (including Clinical Dementia Rating Scale [CDR], Montreal Cognitive Assessment, and Craft Story) at baseline and annual follow-up (Mfollow-up=3.4 years). CCI-40 includes the original 20 items (CCI-20) and the first 12 memory items (CCI-12). Linear mixed effects models (LME) and generalized LME assessed the association of CCI total scores at baseline with rate of decline in neuropsychological tests and CDR. In the overall sample and across predementia groups, the CCI was associated with rate of change in log odds on CDR, with higher CCI at baseline predicting faster increase in the odds of being impaired on CDR. The predictive validity of the CCI broadly held across versions (CCI-12, 20, 40) and ethnic/racial groups (non-Hispanic black and white). Self-perception of cognitive change on the CCI is a useful marker of dementia risk in demographically/clinically diverse nondemented samples. All CCI versions successfully predicted decline.

Impact of motor task conditions on end-point kinematics and trunk movements during goal-directed arm reach

Task conditions significantly impact human motor control. We investigated how task type, difficulty, and constraints influence the kinematics of goal-directed arm reaching. Non-disabled young adults performed two distinct goal-directed arm reaching tasks: pointing and picking up an object with chopsticks. These tasks were carried out under various conditions, including constrained and unconstrained elbow extension and two different task difficulties. We collected kinematic data using a 3-D motion capture system and analyzed the effects of different task conditions on kinematic variables using linear mixed-effects regression analysis. Our findings revealed statistically significant differences in kinematics between the two tasks. Arm reaching during the picking-up task was slower and exhibited jerkier movements compared to the pointing task. Additionally, when arm reaching was performed with constrained elbow extension, it led to slower and jerkier movements, with an increased involvement of trunk movements compared to the unconstrained condition. These findings show that complex manipulative motor tasks requiring higher hand dexterity necessitate feedback-based control of arm reaching, but simple pointing tasks requiring less hand dexterity do not. In conclusion, our study sheds light on the influence of task conditions on goal-directed arm reaching kinematics and provides valuable insights into the motor control strategies involved in different tasks.

Cultural adaptation and validation of the Sinhala version of the Frail Non-disabled tool (FiND)

BackgroundFrailty, a common geriatric syndrome of vulnerability, is associated with a decline in health and function. The most problematic expression of population ageing is associated with weakness, slowing, decreased energy, lower activity and when severe, unintended weight loss. Frailty is not consciously identified in clinical practice and is not widely studied in Sri Lanka. A validated tool for screening frailty in a busy clinical setting is therefore much needed. This study was done as a part of validating the Sinhala version of the Frail Non-Disabled (S-FiND) tool.MethodsThe FiND tool was translated from English to Sinhala by two translators, blinded to each other. They were combined and translated back to the original language by two separate translators. After verifying the content validity, unambiguity and clarity of items in a focused group discussion, the pre-final version was piloted among 30 volunteers. After assessing the psychometric properties of the pre-final version, the final version was tested among 100 adults older than 65 years from the Colombo South Teaching Hospital. The tool was compared with Fried’s frailty phenotype taken as the gold standard.ResultsData were analysed for the agreement with the reference standard, the Fried Phenotype. The mean (SD) age of subjects was 73.9 (7.8) years. The overall time taken to fill out the questionnaire was 2 min. The agreement (Kappa) between the S-FiND questionnaire and the Fried phenotype was 0.7 (P < 001). The sensitivity and specificity of FiND in detecting frailty were 92% and 74%, respectively. The agreements (Kappa) between the individual items of S-Find: involuntary loss of weight/ more than 4.5 kg over one year, the feeling of effort/ not getting going and level of physical activity, with the Fried phenotype, were 0.28 (p = 0.001), 0.06 (p = 0.045) and 0.339 (p < 0.001). respectively. When subjects were categorized frail and robust based on FiND, frail subjects reported a higher incidence of falls (50%) during the previous 12 months, compared to those robust (13%) (p < 0.001 for Chi stat).ConclusionThe S-FiND is a reliable, valid and well-received tool that can be used in detecting the frailty of non-disabled Sinhala-speaking older adults.

Using high-resolution imaging to study the impact of the Kalogon wheelchair cushion on blood flow in the gluteal area

This study investigated how the air-bladder offloading mode of the Orbiter by Kalogon wheelchair cushion (Orbiter) affected blood flow in the gluteal region of non-disabled subjects. The hypothesis was that the cushion's offloading mode would improve blood flow, resulting in reduced reactive hyperemia when compared to the static setting, or Loaded Control (LC). Furthermore, the study proposed a technique using a high-resolution image laser speckle contrast system to measure blood flow in the gluteal area. Two procedures were carried out, one with the participant sitting on a cushion in LC, and the second, the cushion was set to offloading mode. Blood flow was measured through data imaging after each procedure. Three trials were performed, starting and ending in different cushion bladders. Customized algorithms were used to select regions of interest on the images for calculations. The Wilcoxon Signed-Rank Test was conducted to compare the offloads and loaded control values of each region of interest. Results were considered significant at α=0.05. Ten healthy, non-disabled adults participated in the study, seven females and three males. There were no significant differences among the participants. However, results showed that seven subjects tended to decrease reactive hyperemia in the offload sequence of trial when the last two bladders offloaded were the sacrum followed by the right ischial tuberosity. The high-resolution imager showed that the Orbiter Offloads helped reduce reactive hyperemia in seven subjects, potentially improving blood flow. More research is necessary to comprehend the mechanisms of these effects fully.

Sex-Specific Association of Body Mass Index with Hippocampal Subfield Volume and Cognitive Function in Non-Demented Chinese Older Adults.

Recent research suggests a possible association between midlife obesity and an increased risk of dementia in later life. However, the underlying mechanisms remain unclear. Little is known about the relationship between body mass index (BMI) and hippocampal subfield atrophy. In this study, we aimed to explore the associations between BMI and hippocampal subfield volumes and cognitive function in non-demented Chinese older adults. Hippocampal volumes were assessed using structural magnetic resonance imaging. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A total of 66 participants were included in the final analysis, with 35 females and 31 males. We observed a significant correlation between BMI and the hippocampal fissure volume in older females. In addition, there was a negative association between BMI and the RBANS total scale score, the coding score, and the story recall score, whereas no significant correlations were observed in older males. In conclusion, our findings revealed sex-specific associations between BMI and hippocampal subfield volumes and cognitive performance, providing valuable insights into the development of effective interventions for the early prevention of cognitive decline.

Amyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes.

Diabetes is associated with cognitive decline, but the underlying mechanisms are complex and their relationship with Alzheimer's Disease biomarkers is not fully understood. We assessed the association of small vessel disease (SVD) and amyloid burden with cognitive functioning in 47 non-demented older adults with type-2 diabetes from the Israel Diabetes and Cognitive Decline Study (mean age 78Y, 64% females). FLAIR-MRI, Vizamyl amyloid-PET, and T1W-MRI quantified white matter hyperintensities as a measure of SVD, amyloid burden, and gray matter (GM) volume, respectively. Mean hemoglobin A1c levels and duration of type-2 diabetes were used as measures of diabetic control. Cholesterol level and blood pressure were used as measures of cardiovascular risk. A broad neuropsychological battery assessed cognition. Linear regression models revealed that both higher SVD and amyloid burden were associated with lower cognitive functioning. Additional adjustments for type-2 diabetes-related characteristics, GM volume, and cardiovascular risk did not alter the results. The association of amyloid with cognition remained unchanged after further adjustment for SVD, and the association of SVD with cognition remained unchanged after further adjustment for amyloid burden. Our findings suggest that SVD and amyloid pathology may independently contribute to lower cognitive functioning in non-demented older adults with type-2 diabetes, supporting a multimodal approach for diagnosing, preventing, and treating cognitive decline in this population.

Review of the determinants contributing to the demographics of Alzheimer’s syndrome: Prevention techniques, risk factors, and insights for public health

Alzheimer's disease (AD) is the leading cause of memory loss, accounting for 80% of cases and severely impacting daily life and social interactions. The prevalence of AD is expected to grow over the globe as life expectancy improves and the population ages in developing countries will result in a costly disease burden. A combination of societal circumstances and inherent sensitivity that extends throughout a person’s lifetime can cause AD, a challenging and varied disorder. This study aims to provide a comprehensive analysis of the factors that shape the demographics of AD, with a focus on prevention measures. risk factors and their public health consequences. Interventions aimed at addressing multiple risk indicators in non-demented older adults, including those in their middle age, can be able to prevent or postpone the development of AD since the illness is thought to begin generations before clinical evidence appears. Addressing the intricate connection between social and psychological characteristics and Alzheimer’s demography is critical for devising effective preventative measures, early treatments and individualized care for at-risk communities. AD is known to be associated with genetic variables, particularly the APOE ε4 allele. Identifying the disease’s genetic causes is essential for specific preventive and early intervention methods. A balanced diet, frequent physical exercise, cognitive stimulation and social involvement are the preventative treatments for AD. Early identification and intervention hold promise for reducing disease development and public health measures that promote knowledge as well as healthy lives are essential.

Association between ApoE ε4 genotype and attentional function in non-demented, middle-aged, and older adults from rural India.

Several genetic factors have been associated with cognitive decline in aging. Apolipoprotein E (ApoE) ε4 has been widely studied in the risk for pathological cognitive decline, including dementia. However, the association between ApoE ε4 and cognitive functioning in the healthy aging Indian population has been understudied, and the results are ambiguous. This study aims to examine the role of the ApoE genotype with attentional function in aging adults (≥45 years) in a rural Indian population. Cross-sectional (baseline) data (n = 2100) was utilized from an ongoing longitudinal cohort study on aging (Srinivaspura Aging, Neurosenescence, and Cognition study). Participants hailed from villages of Srinivaspura in Karnataka, southern India. Participants were categorized based on ApoE-ε4 status into three categories: No ε4, heterozygous ε4, and homozygous ε4. Attentional function was assessed using the auditory and visual attention subtests from a computerized neurocognitive test battery. Linear regression was performed adjusting for age, gender, and education. In model 1 (unadjusted), we did not find an association between ApoE and attention function. In the partially adjusted model 2 (adjusting for age), ApoE ε4 with age was significantly associated with the attention function. Further, with increasing age, there was a decline in attention among homozygous ε4 individuals. Model 3 (model 2 + gender) found that ApoE ε4, age, and gender explained a significant variance in attention function. In addition, with increasing age, males had poor attention in the homozygous as compared to heterozygous group. Model 4 (model 3+ education) explained a significant variance in attention and also revealed that with increasing age, attention declined in the illiterate and low literacy groups in both homozygous and heterozygous groups among both genders. Although ApoE ε4 alone was not associated, it interacted with age, gender, and education to affect attention function in this rural Indian population. Longitudinal cognitive monitoring will yield insights into understanding whether the ApoE ε4 genotype influences the rate of cognitive decline in this rural, aging population.

Predicting Cognitive Decline for Non-Demented Adults with High Burden of Tau Pathology, Independent of Amyloid Status.

Abnormal tau proteins are independent contributors to cognitive impairment. Nevertheless, not all individuals exposed to high-level tau pathology will develop cognitive dysfunction. We aimed to construct a model to predict cognitive trajectory for this high-risk population. Longitudinal data of 181 non-demented adults (mean age= 73.1; female= 45%), who were determined to have high cerebral burden of abnormal tau by cerebrospinal fluid (CSF) measurements of phosphorylated tau (ptau181) or total tau, were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Cognitive decline was defined as Mini-Mental State Examination scores decline ≥ 3 over three years. A predictive nomogram was constructed using stepwise backward regression method. The discrimination, calibration, and clinical usefulness of the nomogram were evaluated. The model was validated in another 189 non-demented adults via a cross-sectional set (n=149, mean age = 73.9, female = 51%) and a longitudinal set (n= 40, mean age = 75, female = 48%). Finally, the relationships of the calculated risk scores with cognitive decline and risk of Alzheimer's disease were examined during an extended 8-year follow-up. Lower volume of hippocampus (odds ratio [OR] = 0.37, p< 0.001), lower levels of CSF sTREM2 (OR = 0.76, p = 0.003), higher scores of Alzheimer's Disease Assessment Scale-Cognitive (OR = 1.15, p = 0.001) and Functional Activities Questionnaire (OR = 1.16, p = 0.016), and number of APOE ε4 (OR = 1.88, p = 0.039) were associated with higher risk of cognitive decline independent of the amyloid status and were included in the final model. The nomogram had an area of under curve (AUC) value of 0.91 for training set, 0.93 for cross-sectional validation set, and 0.91 for longitudinal validation set. Over the 8-year follow-up, the high-risk group exhibited faster cognitive decline (p< 0.001) and a higher risk of developing Alzheimer's dementia (HR= 6.21, 95% CI= 3.61-10.66, p< 0.001 ). APOE ε4 status, brain reserve capability, neuroinflammatory marker, and neuropsychological scores can help predict cognitive decline in non-demented adults with high burden of tau pathology, independent of the presence of amyloid pathology.

Anti-Hypertensive Drugs Moderate the Relationship of Blood Pressure with Alzheimer's Pathologies and Neurodegenerative Markers in Non-Demented Hypertensive Older Adults.

We aimed to explore whether the relationships of blood pressures (BPs) with Alzheimer's disease (AD) endophenotypes varied by usage of antihypertensive drugs (AHDs). A total of 765 non-demented older adults (mean age: 74.4 years; female: 43.1%) with a self-reported history of hypertension were followed for 6 years. Multiple linear regression and linear-mixed effect models were used to investigate the interaction effects of five categories of AHDs (angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARBs], β-blocker, calcium channel blockers [CCB], diuretic) with BPs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) on AD core pathology and neurodegenerative markers. After Bonferroni correction, significant interaction effects of BPs with AHDs were observed. Elevated SBP or PP in late-life was associated with higher levels of cerebral Aβ burden (diuretic alone/β-blocker × SBP), higher levels of CSF tau proteins (diuretic × SBP/PP, ARBs/CCB × SBP), and lower volume of entorhinal region (β-blocker × SBP, diuretic × PP) only among hypertensive patients who received no anti-hypertensive treatments, while these associations became compromised or null for users of specific AHDs except for ACEI. Compared to taking other classes of AHDs, elevated SBP in late-life was associated with lower cerebral Aβ burden in diuretic users (padjusted = 0.08) and was associated with higher CSF tau proteins in ACEI alone users (padjusted = 0.03). Longitudinal data validated the above-mentioned interaction effects on changes of cerebral Aβ burden (padjusted < 0.05), CSF tau proteins (padjusted < 0.10), and brain atrophy (padjusted < 0.05). The relationships of late-life BP with AD pathology and neurodegeneration could be modified by anti-hypertensive treatments and varied by AHD classification. These findings provide preliminary evidence for tailored BP management strategy for preventing AD among late-life hypertensive adults.