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The reported primary dementia-protective benefits of angiotensin II type 1 receptor (AT(1)R) blockers (ARB) are believed, at least in part, to arise from systemic effects on blood pressure. However, there is a specific and independently regulated brain renin-angiotensin system (RAS). Brain RAS acts mainly through three receptor subtypes; AT(1)R, AT(2)R, and AT(4)R. The AT(1)R promotes inflammation and mitochondrial reactive oxygen species generation. AT(2)R increases nitric oxide. AT(4)R is essential for dopamine and acetylcholine release. It is unknown whether ARB use is associated with changes in the brain RAS. Here, we compared the impact of treatment with ARB on not cognitively impaired individuals and individuals with Alzheimer’s dementia using postmortem frontal-cortex samples of age- and sex-matched participants (70–90 years old, n = 30 in each group). We show that ARB use is associated with higher brain AT(4)R, lower oxidative stress, and amyloid-β burden in NCI participants. In AD, ARB use was associated with lower brain AT(1)R but had no impact on inflammation, oxidative stress, or amyloid-β burden. Our results may suggest a potential role for AT(4)R in the salutary effects for ARB on the brains of not cognitively impaired older adults. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00639-8.

Supplemental Material, sj-pdf-1-jah-10.1177_08982643211011799 for Healthcare-Seeking Behaviors Among Medicare Beneficiaries by Functional Hearing Status by Heng-Yu H. Lin, Amber Willink, Anna M. Jilla, Heather M. Weinreich, Esther S. Oh, Mariah Robertson, Hannah V. Ward and Nicholas S. Reed in Journal of Aging and Health

Supplemental Material, sj-pdf-1-jah-10.1177_08982643211011799 for Healthcare-Seeking Behaviors Among Medicare Beneficiaries by Functional Hearing Status by Heng-Yu H. Lin, Amber Willink, Anna M. Jilla, Heather M. Weinreich, Esther S. Oh, Mariah Robertson, Hannah V. Ward and Nicholas S. Reed in Journal of Aging and Health

The primary dementia-protective benefits of Angiotensin receptor type 1 (AT1R) blockers (ARBs) are believed to arise from systemic effects on blood pressure. However, there is a brain-specific renin-angiotensin system (b-RAS) that acts mainly through three receptor subtypes: AT1R, AT2R, and AT4R. AT1R promotes inflammation and oxidative stress (OS). AT2R increases nitric oxide. AT4R is essential for dopamine release and mediates memory consolidation. Here, we aimed to investigate the effects of ARBs on b-RAS, OS, inflammation, PHF-tau, and beta-amyloid load. Postmortem frontal-cortex brains of age- and sex-matched cognitively intact (CI) individuals using (n=30) and not using ARBs (n=30) and Alzheimer's disease (AD) patients using (n=30) and not using ARBs (n=30) were studied. Protein levels of receptors were measured by Western blot. Protein carbonyl (PC) and cytokine levels were measured by ELISA. Tangle and amyloid-β scores were used as outcomes. In CI individuals, our data shows that ARB treatment was associated with higher protein levels of AT4R (median(range) 0.69(1.92) vs 0.17(1.18) CI+ARBs vs CI, p=0.02), lower level of OS marker PC (10.60(8.32) vs 11.26(7.44), CI+ARBs vs CI, p=0.03) and lower hippocampal and overall amyloid scores (0(5.45) vs 1.15(4.21) p=0.03, 0.79(12.75) vs 3.41(13.36) p=0.04, CI+ARBs vs CI, respectively). In AD group, ARB treatment was associated with lower AT1R protein levels (0.47(1.15) vs 0.59(1.99), AD+ARBs vs AD, p=0.02). No significant changes were observed in OS, inflammation, or PHF-tau and amyloid load in AD brains treated with ARBs. Our results highlight the impact of ARBs on the brains of cognitively intact and AD older individuals.

Hearing loss is one of the most common comorbidities among persons with dementia, with prevalence of 60->90%. Most go untreated and disparities exist. However, sensory impairment may influence the health of individuals and care partners. We will share findings from a clinic-based cohort of persons with dementia (n=101). Controlling for demographic and clinical factors, we found that every 10 decibel increase in hearing loss was associated with nearly an additional neuropsychiatric symptom (b = 0.7 per 10 dB; p = 0.01) and 1.3-point increase in severity (b = 1.3 per 10 dB; p = 0.04). These findings provide the first estimates that utilize objective audiometry. Furthermore, hearing aid use appeared to be protective. Hearing care may represent an additional, but underutilized, non-pharmacological intervention. We will discuss these findings in the context of the epidemiology of hearing loss in dementia and highlight new opportunities for managing hearing loss through community-based approaches.

During the COVID-19 pandemic, telehealth has become an important means of delivering memory care. Telehealth that is responsive to the technological abilities and preferences as well as the sensory needs of persons living with dementia is critical to advancing access to care. We conducted a systematic review to investigate the use of telehealth among older adults with cognitive impairment. The search yielded 3,551 titles and abstracts that led to 17 full-text articles. Studies showed that telehealth can be used for routine care, cognitive assessment and telerehabilitation with good efficacy and satisfaction. Three studies investigated telemedicine delivery in the home and 16/17 studies relied on support staff and care partners to navigate technology. No studies reported adaptations to account for sensory impairments and 5/17 studies excluded individuals with sensory impairments. This talk will review barriers and facilitators totelehealth for older adults with cognitive impairment and adaptations to address sensory needs.

IntroductionPlasma levels of amyloid-beta (Aβ) do not correlate well with different stages of Alzheimer's disease (AD) in cross-sectional studies. Measuring the changes in Aβ plasma levels with an acute intervention may be more sensitive to distinguishing individuals in earlier stages of AD (mild cognitive impairment; MCI) from normal controls.Methods57 participants (18 with AD/MCI and 39 cognitively normal controls) underwent oral glucose tolerance testing (OGTT). Blood samples were obtained over a 2 hour time period. Changes in plasma Aβ40 and42 levels were measured from either baseline or 5 minutes to the 10 minute time point.ResultsCompared to normal controls, subjects with AD/MCI had significantly less change (Δ) in plasma levels for both Aβ40(-3.13(40.93)pg/ml vs. 41.34(57.16)pg/ml;p=0.002) and Aβ42(-0.15(3.77)pg/ml vs. 5.64(10.65)pg/ml; p=0.004).DiscussionOGTT combined with measures of plasma Aβ40 and 42 is potentially useful in distinguishing aging individuals who are in different stages of AD.

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise “state-of-the-science” report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.