Underrepresented and Underserved Populations in Neurological Research.

Underserved and underrepresented populations have historically been excluded from neurological research. This lack of representation has implications for translation of research findings into clinical practice given the impact of social determinants of health on neurological disease risk, progression, and outcomes. Lack of inclusion in research is driven by individual-, investigator-, and study-level barriers as well as larger systemic injustices (e.g., structural racism, discriminatory practices). Although strategies to increase inclusion of underserved and underrepresented populations have been put forth, numerous questions remain about the most effective methodology. In this article, we highlight inclusivity patterns and gaps among the most common neurological conditions and propose best practices informed by our own experiences in engagement of local community organizations and collaboration efforts to increase underserved and underrepresented population participation in neurological research.

Scalable plasma and digital cognitive markers for diagnosis and prognosis of Alzheimer's disease and related dementias.

INTRODUCTION: With emergence of disease-modifying therapies, efficient diagnostic pathways are critically needed to identify treatment candidates, evaluate disease severity, and support prognosis. A combination of plasma biomarkers and brief digital cognitive assessments could provide a scalable alternative to current diagnostic work-up. METHODS: We examined the accuracy of plasma biomarkers and a 10-minute supervised tablet-based cognitive assessment (Tablet-based Cognitive Assessment Tool Brain Health Assessment [TabCAT-BHA]) in predicting amyloid ß positive (Aß+) status on positron emission tomography (PET), concurrent disease severity, and functional decline in 309 older adults with subjective cognitive impairment (n = 49), mild cognitive impairment (n = 159), and dementia (n = 101). RESULTS: Combination of plasma pTau181, Aß42/40, neurofilament light (NfL), and TabCAT-BHA was optimal for predicting Aß-PET positivity (AUC = 0.962). Whereas NfL and TabCAT-BHA optimally predicted concurrent disease severity, combining these with pTau181 and glial fibrillary acidic protein was most accurate in predicting functional decline. DISCUSSION: Combinations of plasma and digital cognitive markers show promise for scalable diagnosis and prognosis of ADRD. HIGHLIGHTS: The need for cost-efficient diagnostic and prognostic markers of AD is urgent. Plasma and digital cognitive markers provide complementary diagnostic contributions. Combination of these markers holds promise for scalable diagnosis and prognosis. Future validation in community cohorts is needed to inform clinical implementation.

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

INTRODUCTION: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population. METHODS: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese. RESULTS: ACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception. DISCUSSION: ACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness. HIGHLIGHTS: The Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

Epidemiology of neurocognitive disorders in adults from urban-marginalized areas: a door-to-door population-based study in Puente Piedra, Lima, Peru.

Background: In Latin America (LA), the prevalence of dementia is expected to triple to 150 million people by 2050. The 2020 Lancet Commission report identified several modifiable dementia risk factors, yet few social and environmental factors, most relevant to vulnerable regions of LA, were highlighted in this report. We sought to assess the epidemiology of neurocognitive disorders (NCD) in Puente Piedra, one of the most socially and economically vulnerable districts of Lima, the capital of Peru. Methodology: This was a cross-sectional door-to-door observational study that used two-stage household sampling. One young adult (30-59 years) and one older adult (>60 years) per household were enrolled. We collected demographic, clinical, and neurocognitive data. Addenbrooke's Cognitive Examination (young adults) and the RUDAS-PE (older adults) were used, classifying participants as cognitively normal, possible mild NCD, or possible major NCD. Results: We enrolled 247 participants (median age 46 years; 67% female). One-fourth had not completed secondary school and more than 50% completed only secondary school. Most participants were housewives (46%) and 21% did not have health insurance. The overall prevalence of possible NCD was 30% (25.6 and 41.8% among younger adults and older adults, respectively). Among younger adults, those ages 55-59 years more frequently had NCD (70%) compared to younger age ranges. Among older adults, only 3 subjects (4.5%) had major NCD. Conclusion: We found a high frequency of possible NCDs in a socially and economically vulnerable community in Lima, Peru, with younger adults showing levels of NCD higher than expected. Our findings support the need for health systems to incorporate cognitive screenings programs for NCD in younger ages. Future research on NCD would include younger populations, particularly in vulnerable communities.

The Memory Alteration Test Is Correlated with Clinical, Cerebrospinal Fluid, and Brain Imaging Markers of Alzheimer Disease in Lima, Peru.

INTRODUCTION: As disease-modifying therapies become available for Alzheimer's disease (AD), detection of AD in early stages of illness (mild cognitive impairment [MCI], early dementia) becomes increasingly important. Biomarkers for AD in low- and middle-income countries (LMICs) are costly and not widely available; hence, it is important to identify cognitive tests that correlate well with AD biomarker status. In this study, we evaluated the memory alteration test (M@T) to detect biomarker-proven AD and quantify its correlation with neurodegeneration and cerebrospinal fluid (CSF) AD biomarkers in a cohort of participants from Lima, Peru. METHODS: This is a secondary analysis of a cohort of 185 participants: 63 controls, 53 with amnestic MCI (aMCI), and 69 with dementia due to AD. Participants underwent testing with M@T and a gold standard neuropsychological battery. We measured total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (ß-amyloid) in CSF, and evaluated neurodegeneration via medial temporal atrophy score in MRI. We used receiver-operator curves to determine the discriminative capacity of the total M@T score and its subdomains. We used the Pearson coefficient to correlate M@T score and CSF biomarkers. RESULTS: The M@T had an area under the curve (AUC) of 0.994 to discriminate between controls and cognitively impaired (aMCI or AD) patients, and an AUC of 0.98 to differentiate between aMCI and AD patients. Free-recall and cued recall had the highest AUCs of all subdomains. Total score was strongly correlated with t-tau (-0.77) and p-tau (-0.72), and moderately correlated with ß-amyloid (0.66). The AUC for discrimination of neurodegeneration was 0.87. CONCLUSION: The M@T had excellent discrimination of aMCI and dementia due to AD. It was strongly correlated with CSF biomarkers and had good discrimination of neurodegeneration. In LMICs, the M@T may be a cost-effective screening tool for aMCI and dementia caused by AD.

Impact of COVID-19 Mandatory Lockdown Measures on Cognitive and Neuropsychiatric Symptoms in Persons with Alzheimer's Disease in Lima, Peru.

BACKGROUND: Neuropsychiatric symptoms (NPS) in patients with Alzheimer's disease (AD) worsened during the COVID-19 lockdowns, but their progression thereafter is unknown. We present the first longitudinal study tracking them before, during, and after restrictions. OBJECTIVES: To describe the effect of the COVID-19 mandatory lockdowns on Cognitive and Neuropsychiatric symptoms in patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). METHODS: Cohort of 48 patients with amnestic MCI and 38 with AD in Lima, Peru. They received three rounds of cognitive (RUDAS, CDR, M@T), behavioral (NPI), and functional (ADCS-ADL) assessments. We assessed the change in score means across the time points and for each domain of NPS and tracked the changes in individual patients. RESULTS: RUDAS declined 0.9 (SD 1.0) from baseline to lockdown and 0.7 (SD 1.0) after restrictions. M@T declined 1.0 (SD 1.5) from baseline to lockdown and 1.4 (SD 2.0) after restrictions. CDR worsened in 72 patients (83.72%) from baseline to post-lockdown. NPI worsened by 10 (SD 8.3) from baseline to lockdown but improved by 4.8 (SD 6.4) after restrictions. Proportionally, 81.3% of all patients had worsened NPS during the lockdowns, but only 10.7% saw an increase thereafter. Improvement was statistically significant for specific NPS domains except hallucinations, delusions, and appetite changes. Anxiety, irritability, apathy, and disinhibition returned to baseline levels. CONCLUSION: Following confinement, cognition continued to decline, but NPS demonstrated either stability or improvement. This highlights the role modifiable risk factors may have on the progression of NPS.

Perceptions of and Knowledge Acquisition about Brain Health and Aging among Latin American Immigrants:A QualitativePaper.

OBJECTIVES: Older immigrants of Latin American descent are disproportionately impacted by dementia, yet little is known about their dementia- and brain health-related knowledge. We explored perspectives on brain health and aging in this population to inform the development of culturally-relevant interventions. METHODS: Individual, semi-structured interviews were conducted with 30 Spanish-speaking immigrants over 60. Questions addressed knowledge about the brain, perceptions of healthy and unhealthy aging, ideas of how to take care of one's brain, and where knowledge was acquired. Responses were analyzed using thematic analysis. RESULTS: The following themes emerged: (1) Descriptions of the brain varied, from anatomy, cognition, and psychology to disease. (2) Perceptions of healthy aging included independence, memory, emotions, and orientation. (3) Ideas of how to care for the brain included physical, social, and cognitive engagement. (4) Knowledge was acquired in childhood, communities, healthcare settings, careers, and media. CONCLUSIONS: Results showed significant variability in knowledge. Findings may be leveraged to improve interventions that address brain health literacy disparities among older Latin American immigrants. CLINICAL IMPLICATIONS: Takeaways involve increasing education about the structure and functions of the brain, promoting realistic understandings of what nonnormative brain aging entails, and increasing knowledge of empirically-supported maintenance approaches. Dissemination may be increased via healthcare providers, community centers, churches, and media.

Neurocognitive health of older adults experiencing homelessness in Oakland, California.

Background and objectives: The homeless population in the US is aging. Cognitive impairment is prevalent in this population, yet little is known about the neurologic etiologies of such impairment. Addressing this gap in knowledge is important because homeless older adults with cognitive impairment due to neurodegenerative disease may need lifelong tailored support to obtain and maintain housing. In this study, we characterized the neurocognitive health of a sample of adults who experienced homelessness for the first time after age 50 using gold standard behavioral neurology examination practices. Methods: We conducted a descriptive cross-sectional study of older adults who first experienced homelessness after age 50. We recruited our sample purposively from an ongoing longitudinal cohort study of adults who were aged 50 and over and homeless when they entered the cohort. For this sub study, we enrolled a convenience sample from those who reported their first episode of homelessness after age 50. We did not exclude individuals based on history of substance use. Neurologists conducted a structured neurocognitive history intake, neurological examination, neuropsychological evaluation, and functional assessment between November 2020 and February 2021. We screened all participants for neurocognitive disorders using gold standard clinical research diagnostic criteria. Results: We evaluated 25 participants, most were men (76%) and Black (84%), with a median age of 61 years. The most common neurocognitive complaints included deficits in recent episodic memory (n = 15, 60%), executive functions (n = 13, 52%), and behavior/mood, with apathy being the most common complaint (n = 20, 80%). Neuropsychological testing revealed a high prevalence of socioemotional deficits (n = 20, 80%). Common neurological examination deficits included difficulties with coordination, such as impaired Luria task (n = 16, 64%), signs of distal peripheral neuropathy (n = 8, 32%), anosmia/hyposmia (n = 4, 21%), and signs of mild Parkinsonism (n = 5, 20%). The most common diagnoses were MCI (n = 7, 28%), bvFTD (n = 4, 16%), AD (n = 4, 16%), and DLB (n = 2, 8%). Discussion: Our findings suggest that neurocognitive concerns and examination deficits are common among older homeless adults. Specific neurocognitive disorders may be overrepresented in this population, particularly frontotemporal disorders. Longitudinal studies involving brain biomarkers are needed to characterize the neurocognitive health of this vulnerable population more precisely.

Substance Use-Related Cognitive Decline in Families with Autosomal Dominant Alzheimer's Disease: A Cohort Study.

BACKGROUND: Cigarette smoking is a known risk factor for Alzheimer's disease (AD). However, the association between neurodegeneration and other substances has not been fully determined. It is of vital importance to evaluate this relationship in populations at high risk of dementia. Since substance use possibly modifies the progression rate of cognitive decline, we studied this association in a unique and well-phenotyped cohort from the University of Antioquia: carriers of the PSEN1-E280A genetic variant. OBJECTIVE: To determine the association between substance use and cognitive decline in carriers of the PSEN1-E280A genetic variant. METHODS: A retrospective cohort study was conducted with 94 carriers and 69 noncarriers recruited between January 2019 and April 2020. A psychiatrist interviewed the participants using the Consumption of Alcohol, Cigarettes and other Substances questionnaire. The participants were also submitted to cognitive evaluation. The relationship between cognitive decline and substance use was explored through a mixed effects regression model. RESULTS: There was an association between cigarettes and better performance on tasks related to perceptual organization, verbal fluency, and memory in carriers. Alcohol had a positive or negative effect on memory according to the type of alcoholic beverage. Results on marijuana use were no conclusive. Coffee was associated with progressive improvements in executive function and verbal fluency. CONCLUSION: Cigarette and alcohol were associated with an improvement of some cognitive assessments, possibly by a survival bias. In addition, coffee was related to improvements in executive function and language; therefore, its short-term neuroprotective potential should be studied.

Thyroid Dysfunction, Vitamin B12, and Folic Acid Deficiencies Are Not Associated With Cognitive Impairment in Older Adults in Lima, Peru.

Background: Reversible etiologies of cognitive impairment are common and treatable, yet the majority of mild cognitive impairment (MCI) and dementia research in Latin America has focused on irreversible, neurodegenerative etiologies. Objective: We sought to determine if thyroid dysfunction and vitamin B12 and folate deficiencies are associated with cognitive disorders among older adults with memory complaints in Lima, Peru. Methods: This was a retrospective review of patients who presented for cognitive evaluations to a multidisciplinary neurology clinic in Lima, Peru from January 2014 to February 2020. We included individuals aged ≥60 years, native Spanish-speakers, with at least a primary school educational level and a complete clinical assessment. Patients had either subjective cognitive decline (SCD), MCI, or dementia. One-way ANOVA and multiple logistic regression analyses were performed. Results: We included 720 patients (330 SCD, 154 MCI, and 236 dementia); the dementia group was significantly older [mean age SCD 69.7 ± 4.1, dementia 72.4 ± 3.7 (p = 0.000)] and had lower folate levels than SCD patients. The MCI group had higher free T3 levels compared with SCD patients. Those with lower TSH had greater dementia risk (OR = 2.91, 95%CI: 1.15-6.86) but not MCI risk in unadjusted models. B12 deficiency or borderline B12 deficiency was present in 34% of the dementia group, yet no clear correlation was seen between neuropsychological test results and B12 levels in our study. There was no association between MCI or dementia and thyroid hormone, B12 nor folate levels in adjusted models. Conclusion: Our findings do not support an association between metabolic and endocrine disorders and cognitive impairment in older Peruvians from Lima despite a high prevalence of B12 deficiency. Future work may determine if cognitive decline is associated with metabolic or endocrine changes in Latin America.

Performance of the Rowland Universal Dementia Assessment Scale for the Detection of Mild Cognitive Impairment and Dementia in a Diverse Cohort of Illiterate Persons From Rural Communities in Peru.

Background: The accurate diagnosis of neurocognitive disorders in illiterate Peruvian populations is challenging, largely owing to scarcity of brief cognitive screening tools (BCST) validated in these diverse populations. The Peruvian version of the Rowland Universal Dementia Assessment Scale (RUDAS-PE) is a BCST that relies minimally on educational attainment and has shown good diagnostic accuracy in an urban illiterate population in Peru, yet its psychometric properties in illiterate populations in rural settings of the country have not been previously investigated. Objectives: To establish the diagnostic accuracy of the RUDAS-PE compared to expert clinical diagnosis using the Clinical Dementia Rating (CDR) Scale in healthy and cognitively impaired illiterate persons living in two culturally and geographically distinct rural communities of Peru. Methods: A cross-sectional, population-based study of residents ≥ 50 years of age living in the Peruvian rural communities of Santa Clotilde and Chuquibambilla. A total of 129 subjects (76 from Santa Clotilde and 53 from Chuquibambilla) were included in this study. Gold standard diagnostic neurocognitive evaluation was based on expert neurological history and examination and administration of the CDR. Receiver operating characteristics, areas under the curve (AUC), and logistic regression analyses were conducted to determine the performance of RUDAS-PE compared to expert gold standard diagnosis. Results: Compared to gold standard diagnosis, the RUDAS-PE was better at correctly discriminating between MCI and dementia than discriminating between MCI and controls in both sites (97.0% vs. 76.2% correct classification in Chuquibambilla; 90.0% vs. 64.7% in Santa Clotilde). In Chuquibambilla, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.4% (optimal cutoff at <18), whereas between MCI and controls it was 82.8% (optimal cutoff at <22). In Santa Clotilde, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.1% (optimal cutoff at <17), whereas between MCI and controls it was 75.5% (optimal cutoff at <21). Conclusions: The RUDAS-PE has acceptable psychometric properties and performed well in its ability to discriminate MCI and dementia in two cohorts of illiterate older adults from two distinct rural Peruvian communities.

Characterization of HIV-Associated Neurocognitive Impairment in Middle-Aged and Older Persons With HIV in Lima, Peru.

Background: With widespread use of antiretroviral medications, people living with HIV (PWH) are living longer worldwide, increasing their risk of developing neurocognitive impairment (NCI). The proportion of Peruvians over age 60 is expected to increase to 25% of the population by 2050, including PWH. Therefore, the problem of aging and NCI, especially in the setting of HIV infection, is uniquely pressing. We sought to study the rates of and risk factors associated with NCI among middle-aged and older PWH in Lima, Peru. Materials and Methods: Sociodemographic, medical (infectious and non-infectious), and psychiatric comorbidity and laboratory data were collected. We administered a brief neuropsychological battery evaluating seven cognitive domains affected in HIV-associated NCI and a depression screening. Cognitive test raw scores were converted to T-scores that were demographically adjusted. Descriptive statistics were performed together with regression (unadjusted and adjusted) analyses to determine potential risk factors for NCI among PWH. Results: This was a cross-sectional study in which 144 PWH aged ≥40 years attending a large HIV clinic in Lima, Peru, were recruited from September 2019 to March 2020. Mean age was 51.6 ± 7.7 years, and mean years of education were 14.0 ± 3.1 with 15% females. Median [interquartile range (IQR)] current CD4 and nadir CD4 were 554 (371, 723) and 179 (83, 291), respectively, and 10% currently had AIDS. The prevalence of NCI was 28.5%, and many demonstrated difficulty with attention and working memory (70%). One-quarter of PWH had mild depression or worse on Patient Health Questionnaire 9 (PHQ-9 ≥ 5). In bivariate analyses, neither a depression history nor a higher PHQ-9 score correlated with NCI. No other non-communicable medical or psychiatric comorbidity nor HIV characteristic was predictive of NCI. Having a positive lifetime history of hepatitis B infection, pulmonary tuberculosis, or syphilis increased risk of NCI (PR 1.72; 95% CI 1.04-2.86) in unadjusted analyses, but not in adjusted analyses. Conclusions: NCI among older Peruvians with HIV was found to be highly prevalent with levels consistent with prior reports of HIV-associated NCI worldwide. Common latent HIV-associated co-infections, including latent syphilis, hepatitis B infection, or pulmonary tuberculosis, may increase the risk of NCI among middle-aged and older PWH in Peru.

The Role of Spirituality in Conceptualizations of Health Maintenance and Healthy Aging Among Latin American Immigrants.

OBJECTIVES: We aimed to investigate ways in which spirituality was conceptualized in relationship to maintaining brain health and healthy aging in a cohort of older adults who immigrated to the United States from diverse regions of Latin America, in order to ultimately develop culturally-tailored brain health promotion approaches. DESIGN: We conducted a qualitative study using semi-structured interviews. SETTING: Participants were recruited from community centers and by a memory care center at a large academic medical center. PARTICIPANTS: We interviewed 30 Spanish-speaking immigrants over age 60. Questions addressed perspectives about the brain, aging, and dementia. Interviews were coded for themes. MEASUREMENTS: Thematic analysis was used to analyze participants' responses. RESULTS: We identified 5 themes: (1) expressing gratitude to God for mental and physical health, (2) putting the onus of life and death in God's hands, (3) using church as a place to socialize and build community as an approach to leading a healthy lifestyle, (4) using prayer as nourishment for the soul and the brain, and (5) gaining inner-peace and calm, and thus maintaining a healthy life, due to a connection with God. CONCLUSION: The incorporation of customized spiritual interventions may be a mechanism by which to increase the effectiveness of brain health promotion efforts.

Assessment of Racial/Ethnic Disparities in Timeliness and Comprehensiveness of Dementia Diagnosis in California.

Importance: The US aging population is rapidly becoming more racially and ethnically diverse. Early diagnosis of dementia is a health care priority. Objective: To examine the associations between race/ethnicity and timeliness of dementia diagnosis and comprehensiveness of diagnostic evaluation. Design, Setting, and Participants: This retrospective cross-sectional study used 2013-2015 California Medicare fee-for-service data to examine the associations of race/ethnicity, individual factors, and contextual factors with the timeliness and comprehensiveness of dementia diagnosis. Data from 10 472 unique beneficiaries were analyzed. The sample was selected on the basis of the following criteria: presence of 1 or more claims; no diagnoses of dementia or mild cognitive impairment in 2013 to 2014; continuous enrollment in Medicare Parts A and B; Asian, Black, Hispanic, or White race/ethnicity; and incident diagnoses of dementia or mild cognitive impairment in January through June 2015. Data analyses were conducted from November 1, 2019, through November 10, 2020. Main Outcomes and Measures: Timeliness of diagnosis, defined as incident diagnosis of mild cognitive impairment vs dementia, and comprehensiveness of diagnostic evaluation, defined as presence of the following services in claims within 6 months before or after the incident diagnosis date: specialist evaluation, laboratory testing, and neuroimaging studies. Results: The sample comprised 10 472 unique Medicare beneficiaries with incident diagnoses of dementia or mild cognitive impairment (6504 women [62.1%]; mean [SD] age, 82.9 [8.0] years) and included 993 individuals who identified as Asian (9.5%), 407 as Black (3.9%), 1255 as Hispanic (12.0%), and 7817 as White (74.6%). Compared with White beneficiaries, those who identified as Asian (odds ratio, 0.46; 95% CI, 0.38-0.56), Black (odds ratio, 0.73; 95% CI, 0.56-0.94), or Hispanic (odds ratio, 0.62; 95% CI, 0.52-0.72) were less likely to receive a timely diagnosis. Asian beneficiaries (incidence rate ratio, 0.81; 95% CI, 0.74-0.87) also received fewer diagnostic evaluation elements. These associations remained significant after adjusting for age, sex, comorbidity burden, neighborhood disadvantage, and rurality. Conclusions and Relevance: These findings highlight substantial disparities in the timeliness and comprehensiveness of dementia diagnosis. Public health interventions are needed to achieve equitable care for people living with dementia across all racial/ethnic groups.

BHA-CS: A novel cognitive composite for Alzheimer's disease and related disorders.

INTRODUCTION: Composite scores based on psychometrically rigorous cognitive assessments are well suited for early diagnosis and disease monitoring. METHODS: We developed and cross-validated the Brain Health Assessment-Cognitive Score (BHA-CS), based on a brief computerized battery, in 451 cognitively normal (CN) and 399 cognitively impaired (mild cognitive impairment [MCI] or dementia) older adults. We investigated its long-term reliability and reliable change indices at longitudinal follow-up (N = 340), and the association with amyloid beta (Aß) burden in the CN subgroup with Aß positron emission tomography (N = 119). RESULTS: The BHA-CS was accurate at detecting cognitive impairment and exhibited excellent long-term stability. Reliable decline over one year was detected in 75% of participants with dementia, 44% with MCI, and 3% of CN. Among CN, the Aß-positive group showed worse longitudinal performance on the BHA-CS compared to the Aß-negative group. DISCUSSION: The BHA-CS is sensitive to cognitive decline in preclinical and prodromal neurodegenerative disease.

Neurodegenerative Disease and the Experience of Homelessness.

Introduction: Today, half of the American homeless population is older than 50 years of age. This shift in age distribution among people experiencing homelessness has challenged our long-held views of the causes of homelessness. Age-related neurological diseases, especially neurodegenerative diseases of the brain (NDDB), may play a role eliciting homelessness in a significant proportion of vulnerable older adults. This article aims to explore relationships between homelessness and NDDB in a cohort of research participants enrolled in observational studies on NDDB at an academic center. Methods: We reviewed charts of the Memory and Aging Center (MAC) of the University of California, San Francisco's database searching for research participants with NDDB that had direct relationship to homelessness. We reviewed all research visits conducted between 2004 and 2018 (N = 5,300). Research participants who had any relationship to homelessness were included in this analysis. NDDB was diagnosed via comprehensive neurological, functional, neuropsychological, and biomarker assessments. Non-parametric tests were used for analysis. Thirteen participants were found to have a direct relationship with homelessness. Seven were female and the median of education was 16 (IR: 12.0-19.5) years. Participants were divided into two groups: Those who experienced homelessness while symptomatic from a NDDB but before formal diagnosis (n = 5, Group 1); and participants with formally diagnosed NDDB who exhibited a new propensity toward homelessness (n = 8, Group 2). Compared to Group 2, participants in Group 1 were younger (p = 0.021) and showed similar results in the neuropsychological evaluation. In both groups, the most prevalent diagnosis was frontotemporal dementia. In Group 1, the majority of participants became homeless in the setting of a fragile socioeconomic situation and informants believed that NDDB contributed or caused their homeless state. In Group 2, a new propensity toward homelessness became manifest in different ways and it stood out that all of these participants were well-supported by family and friends during their illness. Conclusions and Relevance: This case series highlights the role that NDDB may have in precipitating homelessness among vulnerable older adults, particularly in the setting of challenging socioeconomic circumstances and unsupportive living environments. Social ramifications of these findings, particularly pertaining to challenges around rehousing these individuals is discussed.

Effect of Collaborative Dementia Care via Telephone and Internet on Quality of Life, Caregiver Well-being, and Health Care Use: The Care Ecosystem Randomized Clinical Trial.

Importance: Few health systems have adopted effective dementia care management programs. The Care Ecosystem is a model for delivering care from centralized hubs across broad geographic areas to caregivers and persons with dementia (PWDs) independently of their health system affiliations. Objective: To determine whether the Care Ecosystem is effective in improving outcomes important to PWDs, their caregivers, and payers beyond those achieved with usual care. Design, Setting, and Participants: A single-blind, randomized clinical trial with a pragmatic design was conducted among PWDs and their caregivers. Each PWD-caregiver dyad was enrolled for 12 months between March 20, 2015, and February 28, 2017. Data were collected until March 5, 2018. Study interventions and assessments were administered over the telephone and internet by clinical and research teams in San Francisco, California, and Omaha, Nebraska. Of 2585 referred or volunteer PWD-caregiver dyads in California, Iowa, or Nebraska, 780 met eligibility criteria and were enrolled. A total of 512 PWD-caregiver dyads were randomized to receive care through the Care Ecosystem and 268 dyads to receive usual care. All eligible PWDs had a dementia diagnosis; were enrolled or eligible for enrollment in Medicare or Medicaid; and spoke English, Spanish, or Cantonese. Analyses were intention-to-treat. Intervention: Telephone-based collaborative dementia care was delivered by a trained care team navigator, who provided education, support and care coordination with a team of dementia specialists (advanced practice nurse, social worker, and pharmacist). Main Outcomes and Measures: Primary outcome measure: Quality of Life in Alzheimer's Disease based on caregiver's rating of 13 aspects of PWD's well-being (including physical health, energy level, mood, living situation, memory, relationships, and finances) on a 4-point scale (poor to excellent). Secondary outcomes: frequencies of PWDs' use of emergency department, hospitalization, and ambulance services; caregiver depression (score on 9-Item Patient Health Questionnaire; higher scores indicate more severe depression); and caregiver burden (score on 12-Item Zarit Burden Interview; higher scores indicate more severe caregiver burden). Results: The 780 PWDs (56.3% female; mean [SD] age, 78.1 [9.9] years) and 780 caregivers (70.9% female; mean [SD] age, 64.7 [12.0] years) lived in California (n = 452), Nebraska (n = 284), or Iowa (n = 44). Of 780 dyads, 655 were still active at 12 months, and 571 completed the 12-month survey. Compared with usual care, the Care Ecosystem improved PWD quality of life (B, 0.53; 95% CI, 0.25-1.30; P = .04), reduced emergency department visits (B, -0.14; 95% CI, -0.29 to -0.01; P = .04), and decreased caregiver depression (B, -1.14; 95% CI, -2.15 to -0.13; P = .03) and caregiver burden (B, -1.90; 95% CI, -3.89 to -0.08; P = .046). Conclusions and Relevance: Effective care management for dementia can be delivered from centralized hubs to supplement usual care and mitigate the growing societal and economic burdens of dementia. Trial Registration: ClinicalTrials.gov identifier: NCT02213458.

Linguistic and Cultural Acceptability of a Spanish Translation of the Ohio State University Traumatic Brain Injury Identification Method Among Community-Dwelling Spanish-Dominant Older Adults.

OBJECTIVE: Our objective was to (1) evaluate the linguistic and cultural acceptability of a Spanish translation of the Ohio State University traumatic brain injury identification method (OSU TBI-ID) and (2) to assess the usability and acceptability of a tablet-based version of this instrument in a cohort of Spanish-dominant older adults. SETTING: University clinical research center and local community center. PARTICIPANTS: Community-dwelling Spanish-dominant adults age 50 years or older without dementia residing in the Bay Area of California (N=22). DESIGN: Cross-sectional cohort study. MAIN OUTCOME MEASURES: Qualitative assessment of linguistic or cultural acceptability of a Spanish translation of the OSU TBI-ID as well as usability or acceptability of a tablet-based self-administered version of this instrument. RESULTS: The Spanish translation had high linguistic and cultural acceptability and was further optimized based on participant feedback. Cognitive interviews to review survey wording revealed high levels of homogeneity in the clinical definitions and synonyms given by participants-for example, results for the clinical term "Quedó Inconsciente/Pérdida (temporal) de la conciencia" (To be unconscious/[Temporary] loss of consciousness) used in the survey included "perder el conocimiento" (loss of consciousness), "knockeado" (knocked out), "No es que esté dormida, porque está inconsciente, pero su corazón está todavía palpitando" (it's not that they're sleeping, because they're unconscious, but their heart is still palpitating). The tablet interface had low observer-based usability, revealing that participants with <13 years of education (n=6) had more difficulty using the tablet which could be improved with minor changes to the coding of the application and minimal in-person technology support. Acceptability of the tool was low among all but 1 participant. CONCLUSION: This linguistically optimized Spanish translation of the OSU TBI-ID is recommended for use as a semistructured interview among Spanish-dominant older adults. Although the tablet-based instrument may be used by interviewers as an efficient electronic case report form among older adults, further research is needed, particularly among older adults with varying levels of education, to validate this instrument as a self-administered survey.

The behavioural variant frontotemporal dementia (bvFTD) syndrome in psychiatry.

The primary goal of this article is to critically discuss the syndromic overlap that exists between early behavioural variant frontotemporal dementia (bvFTD)--the most common clinical syndrome associated with frontotemporal lobar degeneration (FTLD)--and several primary psychiatric disorders. We begin by summarising the current state of knowledge regarding FTLD, including the recent discovery of FTLD-causative genetic mutations. Clinicopathological correlations in FTLD are subsequently discussed, while emphasising that clinical syndromes of FTD are dictated by the distribution of FTLD pathology in the brain. We then review a large number of cases with suspected and confirmed bvFTD that had previously been diagnosed with a primary psychiatric disorder. The clinical and neuroscientific implications of this overlap are discussed, focusing on the importance of early diagnosis for clinical and therapeutic reasons. We propose that largely due to the paucity of biomarkers for primary psychiatric disorders, and the limited use of FTLD-related biomarkers by psychiatrists at present, it is very difficult to separate patients with early bvFTD from those with primary psychiatric disorders based on clinical grounds. Furthermore, specific limitations of the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 criteria for bvFTD may inadvertently discourage recognition of bvFTD in mental health settings. Clinically, more research is needed to develop tools that allow early differentiation of bvFTD from primary psychiatric disease, as bvFTD therapies will likely be most effective in the earliest stages of disease. From a neuroscience perspective, we argue that bvFTD provides an excellent paradigm for investigating the neural basis of psychiatric disorders.

Evaluating and treating neurobehavioral symptoms in professional American football players: Lessons from a case series.

In the aftermath of multiple high-profile cases of chronic traumatic encephalopathy (CTE) in professional American football players, physicians in clinical practice are likely to face an increasing number of retired football players seeking evaluation for chronic neurobehavioral symptoms. Guidelines for the evaluation and treatment of these patients are sparse. Clinical criteria for a diagnosis of CTE are under development. The contribution of CTE vs other neuropathologies to neurobehavioral symptoms in these players remains unclear. Here we describe the experience of our academic memory clinic in evaluating and treating a series of 14 self-referred symptomatic players. Our aim is to raise awareness in the neurology community regarding the different clinical phenotypes, idiosyncratic but potentially treatable symptoms, and the spectrum of underlying neuropathologies in these players.