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Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer's Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer's Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer's Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically confirmed, provided statistical power to test for risk alleles with large effect size. A two-tier study design included GWAS from cohorts #1-3 (Stage I) to identify promising SNP candidates, followed by focused evaluation of particular SNPs in cohorts #4-5 (Stage II). Polymorphism in the ATP-binding cassette, sub-family C member 9 (ABCC9) gene, also known as sulfonylurea receptor 2, was associated with HS-Aging pathology. In the meta-analyzed Stage I GWAS, ABCC9 polymorphisms yielded the lowest p values, and factoring in the Stage II results, the meta-analyzed risk SNP (rs704178:G) attained genome-wide statistical significance (p = 1.4 × 10(-9)), with odds ratio (OR) of 2.13 (recessive mode of inheritance). For SNPs previously linked to hippocampal sclerosis, meta-analyses of Stage I results show OR = 1.16 for rs5848 (GRN) and OR = 1.22 rs1990622 (TMEM106B), with the risk alleles as previously described. Sulfonylureas, a widely prescribed drug class used to treat diabetes, also modify human ABCC9 protein function. A subsample of patients from the NACC database (n = 624) were identified who were older than age 85 at death with known drug history. Controlling for important confounders such as diabetes itself, exposure to a sulfonylurea drug was associated with risk for HS-Aging pathology (p = 0.03). Thus, we describe a novel and targetable dementia risk factor.

The article discusses strategies that investigators may consider to enhance inclusivity of older African American adults in mental health research. These include enhancing representation of African American investigators, engaging participation by older African American adults in research, assessing race and ethnicity in mental health research, considering intersectionality and employing health disparities model in design and interpretation of research and recognizing resiliency and resistance.

African Americans (AAs) have an elevated risk of developing dementia, yet are underrepresented in clinical research. This project uses a community-engaged photovoice approach to add to existing understanding of barriers and facilitators to AA participation in Alzheimer's disease research and identify strategies to enhance engagement. Three AA research advocates served as community facilitators to identify and guide groups of AA adults through an eight to nine session photovoice project. Group sessions involved discussions and sharing of images pertaining to various prompts in the area of brain health and research participation. Sessions were audiotaped and transcribed verbatim. Participants identified three categories of barriers to AA research participation: (a) Mistrust, (b) avoidance and fear of acknowledging problems, and (c) seeing the risks of research but not the need. Participants shared suggestions and approaches for ameliorating each of these barriers. This process revealed unique insights into barriers and opportunities for increasing AA engagement in aging and dementia research. [ABSTRACT FROM AUTHOR]

Importance: There is substantial evidence demonstrating racial disparities in the survival outcomes of patients with head and neck cancer. The reporting and representation of race and ethnicity in cancer trials is crucial for generalizability of trial results to patient care and reduction of racial health disparities in head and neck cancers. Racial disparities in oncologic outcomes across various therapeutic interventions may only manifest when diverse races are appropriately represented in trials., Objective: To characterize the reporting and representation of race and ethnicity in head and neck cancer clinical trials., Evidence Review: A systematic search of published trials and those available on ClinicalTrials.gov was conducted to identify 3973 studies from 2010 to 2020. Title, abstract, and full-text review yielded 155 trials for data extraction of patient demographics. Year of publication, type of intervention, publication source, and funding source were also collected. Race and ethnicity data were compared with Surveillance, Epidemiology, and End Results (SEER) Program cancer registry data., Findings: Of the 155 included studies, only 89 (57%) reported race or ethnicity. Only 81 (52%) of the studies reported detailed classification of race or ethnicity per the US Census Bureau classification scheme. Race and ethnicity reporting varied considerably with year of publication, type of intervention, data source, and funding source. Studies in the latter half of the decade were more likely to report race or ethnicity (odds ratio, 2.78; 95% CI, 1.33-5.80), with the highest number in 2019 (24 of 30 [80%] trials), followed by 2020 (20 of 29 [69%] trials). Among the possible interventions, trials on therapeutic chemoradiation most frequently reported race or ethnicity (11 of 12 [92%]), followed by supportive drug trials (22 of 31 [71%]), and then therapeutic chemotherapy trials (28 of 48 [58%]). When compared with SEER data, race and ethnicity distribution in clinical trials showed fewer Black patients (10% vs 8%) and Asian or Pacific Islander patients (6% vs 2%)., Conclusions and Relevance: In this systematic review, nearly half of head and neck cancer trials in the past decade did not report the race or ethnicity of participants. Participation of Black and Asian or Pacific Islander patients does not adequately reflect the US population's head and neck cancer demographics, limiting the generalizability of trial results and adding to racial health disparities in patients with head and neck cancers.