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1. Global rural health disparities in Alzheimer's disease and related dementias: State of the science

   https://doi.org/10.1002/alz.13104  

   Wiese, Lisa Ann Kirk ; Gibson, Allison ; Guest, Marc Aaron ; Nelson, Amy R. ; Weaver, Raven ; Gupta, Aditi ; Carmichael, Owen ; Lewis, Jordan P. ; Lindauer, Allison ; Loi, Samantha ; et al ( May 2023 , Alzheimer's & Dementia)

   Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place‐based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators.

   An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: “What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?” In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings.

   A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions.

   A location dynamics model and ADRD‐focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities.

   Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities.

   Defining the unique rural barriers and facilitators to cognitive health yields insight.

   The strengths and resilience of rural residents can mitigate ADRD‐related challenges.

   A novel “location dynamics” model guides assessment of rural‐specific ADRD issues.

    

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2. Drug therapies for chronic conditions and risk of Alzheimer's disease and related dementias: A scoping review

   https://doi.org/10.1002/alz.12175  

   Thunell, Johanna ; Chen, Yi ; Joyce, Geoffrey ; Barthold, Douglas ; Shekelle, Paul G. ; Brinton, Roberta Diaz ; Zissimopoulos, Julie ( October 2020 , Alzheimer's & Dementia)

   Most older Americans use drug therapies for chronic conditions. Several are associated with risk of Alzheimer's disease and related dementias (ADRD).

   A scoping review was used to identify drug classes associated with increasing or decreasing ADRD risk. We analyzed size, type, and findings of the evidence.

   We identified 29 drug classes across 11 therapeutic areas, and 404 human studies. Most common were studies on drugs for hypertension (93) or hyperlipidemia (81). Fewer than five studies were identified for several anti‐diabetic and anti‐inflammatory drugs. Evidence was observational only for beta blockers, proton pump inhibitors, benzodiazepines, and disease‐modifying anti‐rheumatic drugs. For 13 drug classes, 50% or more of the studies reported consistent direction of effect on risk of ADRD.

   Future research targeting drug classes with limited/non‐robust evidence, examining sex, racial heterogeneity, and separating classes by molecule, will facilitate understanding of associated risk, and inform clinical and policy efforts to alleviate the growing impact of ADRD.

    

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3. Cardiovascular risk and midlife cognitive decline in the Study of Women's Health Across the Nation

   https://doi.org/10.1002/alz.12300  

   Derby, Carol A. ; Hutchins, Franya ; Greendale, Gail A. ; Matthews, Karen A. ; Sternfeld, Barbara ; Everson‐Rose, Susan A. ; Kazlauskaite, Rasa ; Whitmer, Rachel A. ; Brooks, Maria M. ( March 2021 , Alzheimer's & Dementia)

   Cardiovascular risk factors in midlife have been linked to late life risk for Alzheimer's disease and related dementias (ADRD). The relation of vascular risk factors on cognitive decline within midlife has been less studied.

   Using data from the Study of Women's Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife.

   Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory.

   Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.

    

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4. The competing risk of death and selective survival cannot fully explain the inverse cancer‐dementia association

   https://doi.org/10.1002/alz.12168  

   Hayes‐Larson, Eleanor ; Ackley, Sarah F. ; Zimmerman, Scott C. ; Ospina‐Romero, Monica ; Glymour, M. Maria ; Graff, Rebecca E. ; Witte, John S. ; Kobayashi, Lindsay C. ; Mayeda, Elizabeth Rose ( September 2020 , Alzheimer's & Dementia)

   We evaluated whether competing risk of death or selective survival could explain the reported inverse association between cancer history and dementia incidence (incidence rate ratio [IRR] ≈ 0.62‐0.85).

   A multistate simulation model of a cancer‐ and dementia‐free cohort of 65‐year‐olds was parameterized with real‐world data (cancer and dementia incidence, mortality), assuming no effect of cancer on dementia (true IRR = 1.00). To introduce competing risk of death, cancer history increased mortality. To introduce selective survival, we included a factor (prevalence ranging from 10% to 50%) that reduced cancer mortality and dementia incidence (IRRs ranged from 0.30 to 0.90). We calculated IRRs for cancer history on dementia incidence in the simulated cohorts.

   Competing risk of death yielded unbiased cancer‐dementia IRRs. With selective survival, bias was small (IRRs = 0.89 to 0.99), even under extreme scenarios.

   The bias induced by selective survival in simulations was too small to explain the observed inverse cancer‐dementia link, suggesting other mechanisms drive this association.

    

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5. Integrating amyloid imaging and genetics for early risk stratification of Alzheimer's disease

   https://doi.org/10.1002/alz.14244  

   He, Bing ; Wu, Ruiming ; Sangani, Neel ; Pugalenthi, Pradeep_Varathan ; Patania, Alice ; Risacher, Shannon_L ; Nho, Kwangsik ; Apostolova, Liana_G ; Shen, Li ; Saykin, Andrew_J ; et al ( September 2024 , Alzheimer's & Dementia)

   Alzheimer's disease (AD) initiates years prior to symptoms, underscoring the importance of early detection. While amyloid accumulation starts early, individuals with substantial amyloid burden may remain cognitively normal, implying that amyloid alone is not sufficient for early risk assessment.

   Given the genetic susceptibility of AD, a multi‐factorial pseudotime approach was proposed to integrate amyloid imaging and genotype data for estimating a risk score. Validation involved association with cognitive decline and survival analysis across risk‐stratified groups, focusing on patients with mild cognitive impairment (MCI).

   Our risk score outperformed amyloid composite standardized uptake value ratio in correlation with cognitive scores. MCI subjects with lower pseudotime risk score showed substantial delayed onset of AD and slower cognitive decline. Moreover, pseudotime risk score demonstrated strong capability in risk stratification within traditionally defined subgroups such as early MCI, apolipoprotein E (APOE) ε4+ MCI,APOEε4– MCI, and amyloid+ MCI.

   Our risk score holds great potential to improve the precision of early risk assessment.

   Accurate early risk assessment is critical for the success of clinical trials.

   A new risk score was built from integrating amyloid imaging and genetic data.

   Our risk score demonstrated improved capability in early risk stratification.

    

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