Smoking as a Marker of Comorbid Vulnerability Among Persons with Probable Posttraumatic Stress Disorder Who Engage in Hazardous Drinking.

Persons with posttraumatic stress disorder (PTSD) compared to those without evince high rates of hazardous drinking, or patterns of alcohol consumption that increase the risk for harmful consequences. One potential marker of vulnerability for PTSD-hazardous drinking comorbidity may be smoking behavior. Individuals with PTSD have a higher prevalence of smoking and smoke at higher rates.

Risk of Incident Cancer in Veterans with Diabetes Who Use Metformin Versus Sulfonylureas.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans. This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfonylureas for diabetes between 2001 to 2012.

Scaling and spreading age-friendly care: Early lessons from the VA National Age-Friendly Action Community.

Background: The Age-Friendly Health System (AFHS) initiative seeks to improve care for older adults through assessing and acting on the 4Ms (What Matters, Medication, Mentation, Mobility). The Department of Veterans Affairs (VA) joined the initiative in 2020, and from 2022 to 2023, VA led its first Age-Friendly Action Community, a 7-month online educational series to teach clinicians about implementing the 4Ms across VA care settings.

Methods: The VA Action Community was designed to spread awareness about Age-Friendly care for older Veterans, improve interprofessional team knowledge for providing care guided by the 4Ms, and support AFHS implementation across multiple care settings.

Trajectories of Resilience-Related Traits and Their Impact on Health Outcomes in Schizophrenia: Results From a 4-Year Longitudinal Study.

Background And Hypothesis: For the rapidly growing population of older people living with schizophrenia (PLWS), psychological resilience, or the capacity to adapt to adversity, is an understudied target for improving health. Little is known about resilience and its longitudinal impact on outcomes among PLWS. This study assesses trajectories of resilience-related traits in PLWS and a nonpsychiatric comparison group (NCs) and longitudinal interactions between resilience and health.

Utility of Candidate Genes From an Algorithm Designed to Predict Genetic Risk for Opioid Use Disorder.

Importance: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.

Objective: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.

Associations of late mid‐life lifestyle with brain and cognitive changes in individuals on the AD vs. non‐AD continuum.

Background: To aid development of prevention strategies, we investigated whether a composite measure of late‐midlife lifestyle health was associated with (1) change in brain tau burden, vascular burden and neurodegeneration and (2) cognitive trajectories when accounting for these brain changes.

Method: We included 324 individuals from the Wisconsin Registry for Alzheimer’s Prevention. Late‐midlife lifestyle was assessed using the Lifestyle for Brain Health (LIBRA) score, encompassing 12 risk‐and protective factors for cognitive decline and dementia.

BDNF Val66Met influences the mediation of sex differences in VLM scores by plasma BDNF in a cohort enriched with risk for Alzheimer‘s disease.

Background: Brain‐derived neurotrophic factor (BDNF)—a key neurotrophin involved in synaptic plasticity, neurogenesis, and neuroprotection—has been shown to mediate sex differences in verbal learning and memory (VLM) ability, but it remains unclear whether this relationship is conditionally dependent upon carriage of the Val66Met polymorphism in the BDNF gene. This study investigates how BDNF carriage influences the mediation of sex differences in VLM scores by plasma BDNF levels in a cohort enriched for AD risk.

Method: Cognitively unimpaired participants in the Wisconsin Registry for Alzheimer’s Prevention (WRAP; n=198, age 63.

Neuroimaging Markers of Microstructural Neurodegeneration are More Sensitive to Cognitive Dysfunction than Hippocampal Volume in Early Alzheimer’s Disease: A Mixed‐Longitudinal Study.

Background: While magnetic resonance imaging (MRI) markers of neurodegeneration are nonspecific to Alzheimer’s disease (AD) pathology, they have been correlated with cognitive dysfunction, and therefore, provide important information pertaining to disease staging. Neurodegeneration in AD is commonly assessed with macrostructural measures of brain atrophy, such as hippocampal volume. However, recent investigations have shown that markers of neural microstructure derived from diffusion MRI (DWI) may provide supplementary insight into the progression of AD pathophysiology.

Associations of education and modifiable lifestyle factors with CSF biomarkers of neurodegeneration, neuroinflammation, and Alzheimer’s disease.

Background: Alzheimer’s disease (AD) and related dementias can have long preclinical phases; thus, midlife intervention and prevention methods could prove efficacious. Multiple health‐related lifestyle factors have been associated with risk for AD. However, research on lifestyle factors has focused on clinical outcomes such as cognitive decline, mild cognitive impairment and/or AD dementia; their associations with potential early changes in cerebrospinal fluid (CSF) biomarkers are less understood.

Obstructive sleep apnea severity is associated with CSF biomarkers of synaptic dysfunction and neuroinflammation in a cohort at risk for AD.

Background: Obstructive sleep apnea (OSA) is associated with hypoxia‐induced neuronal impairment and dysfunction—key risk factors for the pathogeneses of age‐related neurodegenerative diseases such as Alzheimer‘s disease (AD). This study examined longitudinal associations between OSA severity and CSF biomarkers associated with AD, synaptic dysfunction, and neuroinflammation in a sample of late‐middle‐aged adults with increased risk for AD.

Method: N=25 cognitively unimpaired adults (64% female, mean age 65.

Plasma pTau217, gender, and synaptic density.

Background: Synaptic loss is a key feature of Alzheimer’s disease (AD) dementia. In the entorhinal cortex (ERC) and hippocampus, phosphorylated tau (pTau) colocalizes with synaptosomes, and its presence may play a role in AD‐related synaptic loss. However, the relationship between pTau and synaptic density is not well understood.

Mid‐life occupational hazardous exposures is associated with late‐life dementia risk in the Wisconsin Longitudinal Study.

Background: Exposures to environmental toxicants and pollutants occur at various points along the life course, with mounting evidence that late‐life pollution exposure increases risk for neurological disease, including dementia. Although occupational hazards constitute a primary source of modifiable environmental exposure during the working years, there is little research examining the protracted effects of mid‐life occupational exposure on late‐life dementia risk.

Method: This study leveraged life course data from the Wisconsin Longitudinal Study (WLS) to evaluate the effects of mid‐life occupational hazardous exposures on late‐life dementia outcomes.

Evaluating Life Simple Seven’s Influence on Brain Health Outcomes: The Intersection of Lifestyle and Dementia.

Background: Lifestyle factors have been studied for their role in dementia, but few have comprehensively assessed both Alzheimer’s disease (AD) and cerebrovascular disease (CBVD) pathologies. This study innovatively integrates AD, CBVD, and cognitive composite scores (CCS) within the same cohort to investigate the association of the Life Simple Seven (LS7) score with a broad spectrum of dementia‐related outcomes. Our research aims to unravel the intricate relationships between lifestyle and various dementia pathologies, challenging conventional research paradigms.

Assessing Clinical Research Barriers to the Participation of Underrepresented Groups in the AHEAD Study.

Background: To increase participation of underrepresented groups (URG) into clinical research studies such as the AHEAD study, a study assessing lecanemab in participants with preclinical Alzheimer’s disease (AD), it is necessary to understand and address barriers in an effort to mitigate them. Toward this goal, methods assessing community needs and plans to meet those needs are imperative. Our ultimate goal is to aid URG in understanding the clinical research process and to empower them to participate in AD research so that approved therapies are applicable to them.

Longitudinal Change in Proper Names from Logical Memory Tasks are Sensitive to Plasma pTau217 Levels.

Background: Previous studies have found connections between recall of proper names (PN) and amyloid positivity in cognitively unimpaired (CU) adults at risk for Alzheimer’s Disease (AD; Mueller et al., 2020). Given the promising prospect of employing plasma‐based biomarkers to determine amyloid burden, we looked at associations between longitudinal change in PN and total score recall from Logical Memory (LM) story recall test and plasma pTau217.

KLOTHO KL‐VS genotype modifies the relationship between cardiorespiratory fitness and CSF biomarkers of neurodegeneration, synaptic dysfunction, and inflammation.

Background: Less adequate cardiorespiratory fitness (CRF) is associated with several aspects of Alzheimer’s disease (AD) pathology, including neuroinflammation, neurodegeneration and synaptic dysfunction, all of which are known contributors to the clinical outcome – progressive cognitive decline [1]. AD‐associated biomolecular changes also seem to be attenuated in carriers of the functionally advantageous variant of the KLOTHO gene (KL‐VS) [2]. While KL‐VS and CRF both appear to mitigate aspects of AD pathology, they have been exclusively studied in isolation.

Cardiorespiratory Fitness Modifies the Association Between Cerebral Pulsatility on Amyloid Burden and Core CSF Biomarkers of Alzheimer’s Disease.

Background: Increasing evidence supports the notion that vascular dysfunction contributes to the evolution of Alzheimer’s disease (AD). Cerebral pulsatility index (PI) is reportedly higher in AD and MCI compared to age matched controls and has been associated with greater beta‐amyloid (Aß) burden. Higher cardiorespiratory fitness (CRF) positively affects vascular function and is associated with lower PI in several large cerebral vessels.

Cardiorespiratory Fitness Modifies the Association of Cerebral Pulsatility on CSF Biomarkers Related to Neurodegeneration, Synaptic Dysfunction, and Neuroinflammation.

Background: Cerebral pulsatility (PI) is reportedly higher in individuals with AD and MCI compared to age matched controls and has been associated with greater beta‐amyloid (Aß) burden, but its relationship to other neurodegenerative biomarkers is unknown. Higher cardiorespiratory fitness (CRF) positively affects vascular function and is associated with lower PI in several large cerebral vessels. The relationship between PI, CRF, and biomarkers for neurodegeneration have not yet been characterized.

Longitudinal neurodegeneration in relation to amyloid pathology among cognitively unimpaired individuals.

Background: The timing of neurodegeneration in relation to the onset of Alzheimer’s disease pathology is not fully known. This study examined the association of longitudinal atrophy derived from T1‐weighted MRI with 1) cerebrospinal fluid (CSF) amyloid‐tau (AT) groupings and 2) Pittsburgh compound B (PiB) PET‐derived estimates of amyloid duration among cognitively unimpaired (CU) individuals.

Method: CU participants in the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center (N = 297) underwent longitudinal MRI, APOE genotyping, and lumbar puncture to determine CSF Aβ42/40 (A) and pTau181 (T) concentration at baseline using in‐house cutoffs.

Menopausal hormone therapy is associated with worse levels of Alzheimer's disease biomarkers in APOE ε4-carrying women: An observational study.

Introduction: Menopausal hormone therapy (MHT), along with the apolipoprotein E (APOE) ε4 allele, has been suggested as a possible risk factor for Alzheimer's disease (AD). However, the relationship between MHT and cerebrospinal fluid (CSF) biomarkers is unknown: we investigated this association, and whether APOE ε4 carrier status moderates it.

Methods: In an observational study of 136 cognitively unimpaired female participants (M = 66.

Neighborhood disadvantage and ADRD pathology assessed with plasma biomarkers.

Background: Neighborhood disadvantage as measured by the Area Deprivation Index (ADI) is associated with Alzheimer’s disease (AD) pathology at autopsy, as well as neuroimaging measures of neurodegeneration. Plasma biomarker assays have emerged as an accessible tool for evaluating ADRD pathology, opening up the possibility of better understanding the effect of neighborhood disadvantage on brain disease among a broader group of research participants. In this study, we evaluated whether neighborhood‐level socioeconomic disadvantage is associated with plasma‐based biomarkers of Alzheimer's disease and related pathology.

What do caregivers of Veterans with dementia feel unprepared for: Results from the multisite HERO CARE caregiver survey.

Background: Veterans with dementia often experience a wide range of multidomain needs, many of which are met by informal caregivers. Yet, caregivers are often not adequately prepared to address the needs of the dementia patient. This study aimed to identify caregiving responsibilities for which informal caregivers feel insufficiently prepared.

Neighborhood Disadvantage and Its Effects on Cognitive Health and Vascular Risk in Veterans.

Background: Prior research has highlighted the impact of neighborhood quality on health outcomes. Given veterans' unique experiences and challenges, exploring the association between neighborhood quality on cognitive measures and vascular risk scores is crucial for guiding targeted interventions, improving overall cognitive well‐being, promoting health equity, and contributing to our understanding of Alzheimer’s Disease (AD) risk factors.

Method: The Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid study (BRAVE) was an 18‐month randomized, placebo‐controlled, double‐blind, clinical trial conducted at William S.

Unmet ADL/IADL Needs among Veterans with Dementia: An Analysis of the HERO CARE Multi‐site Survey.

Background: Receiving sufficient assistance with ADLs/IADLs can support dementia patients’ physical and psychosocial health, as well as aging in place. The Department of Veterans Affairs has prioritized supporting Veterans in aging at place a home when this is their preference. We aimed in the current study to analyze if there are demographic characteristics and/or comorbidities of Veterans with dementia that are predictive of having unmet ADL/IADL needs.

Associations between Neighborhood‐Level Disadvantage and Neuroimaging Markers of Microstructural Neurodegeneration Across the Alzheimer’s Disease Continuum: A Mixed‐Longitudinal Study.

Background: Residence in highly socioeconomically disadvantaged neighborhoods has recently been associated with Alzheimer’s disease (AD) neuropathology at autopsy, cognitive decline, and magnetic resonance imaging (MRI) markers of volumetric brain atrophy in cognitively unimpaired adults. Furthermore, there is mounting evidence that markers of brain microstructure derived from diffusion‐weighted MRI (DWI), including neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISO), are sensitive to AD‐related neurodegeneration. In this study, we used linear mixed‐effects (LME) modeling to investigate the hypothesis that neighborhood‐level disadvantage is associated with mixed‐longitudinal trajectories of microstructural neurodegeneration in 539 late‐middle‐aged participants across the AD continuum.