Characterizing Multimorbidity Prevalence and Adverse Outcomes in Ethnically and Culturally Diverse Sub-Populations in India: Gaps, Opportunities, and Future Directions.

India is a large middle-income country and has surpassed China in overall population, comprising 20% of the global population (over 1.43 billion people). India is experiencing a major demographic shift in its aging population. Chronic diseases are common among older adults and can be persistent over the life course, lead to the onset of disability, and be costly. Among older adults in India, the existence of multiple comorbid chronic conditions (i.e., multimorbidity) is rapidly growing and represents a burgeoning public health burden. Prior research identified greater rates of multimorbidity (e.g., overweight/obesity diabetes, hypertension, cardiovascular disease, stroke, and malignancies) in minority populations in the United States (U.S.); however, limited studies have attempted to characterize multimorbidity among older adult sub-populations residing in India. To address this gap, we conducted a narrative review of studies on multimorbidity using the data from the Longitudinal Aging Study of India (LASI), the largest nationally representative longitudinal survey study of adults in India. Our definition of multimorbidity was the presence of more than two conditions in the same person. Our findings, based on 15 reviewed studies, aim to (1) characterize the definition and measurement of multimorbidity and to ascertain its prevalence in ethnically and culturally diverse sub-populations in India; (2) identify adverse outcomes associated with multimorbidity in the Indian adult population; and (3) identify gaps, opportunities, and future directions.

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.

C9orf72 Repeat Expansion Initially Presenting as Late-Onset Bipolar Disorder With Psychosis.

INTRODUCTION: C9orf72 expansion is the most common genetic abnormality in behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis. Although psychiatric prodromes are common in C9orf72 expansion carriers, there are only scattered reported cases of primary psychiatric disorders, such as bipolar disorder, diagnosed at disease onset. Moreover, C9orf72 carrier status is rarely identified in bipolar disorder genetic studies. CASE REPORT: A 51-year-old, right-handed woman with 16 years of education presented for evaluation of long-standing cognitive and behavioral change. She initially displayed symptoms of mania and florid, multimodal psychotic symptoms at age 39. Her bipolar disorder symptoms were initially responsive to medication; however, she later developed executive dysfunction and behavioral symptoms consistent with bvFTD. She became progressively nonverbal, and her limited speech was notable for speech apraxia. At the time of presentation, she demonstrated cortical sensory deficit, ideomotor and oral-buccal apraxia, and unstable gait. Neuroimaging revealed diffuse brain atrophy. Postmortem histopathological evaluation revealed frontotemporal lobar degeneration with TDP-43 inclusions, type B, and genetic study identified C9orf72 expansion. A detailed review of family history found a strong paternal history of bipolar disorder and substance use disorder. CONCLUSIONS: We describe a rare case of C9orf72 expansion initially characterized by late-onset bipolar disorder and florid, multimodal psychotic symptoms, followed years later by bvFTD diagnosis. This report emphasizes the importance of completing a neurological examination, obtaining a detailed family history, and pursuing genetic screening to distinguish between primary psychiatric disorder and bvFTD in individuals who meet the criteria for late-onset bipolar disorder.

Assessing processing speed and its neural correlates in the three variants of primary progressive aphasia with a non-verbal tablet-based task.

Prior research has revealed distinctive patterns of impaired language abilities across the three variants of Primary Progressive Aphasia (PPA): nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). However, little is known about whether, and to what extent, non-verbal cognitive abilities, such as processing speed, are impacted in PPA patients. This is because neuropsychological tests typically contain linguistic stimuli and require spoken output, being therefore sensitive to verbal deficits in aphasic patients. The aim of this study is to investigate potential differences in processing speed between PPA patients and healthy controls, and among the three PPA variants, using a brief non-verbal tablet-based task (Match) modeled after the WAIS-III digit symbol coding test, and to determine its neural correlates. Here, we compared performance on the Match task between PPA patients (n = 61) and healthy controls (n = 59) and across the three PPA variants. We correlated performance on Match with voxelwise gray and white matter volumes. We found that lvPPA and nfvPPA patients performed significantly worse on Match than healthy controls and svPPA patients. Worse performance on Match across PPA patients was associated with reduced gray matter volume in specific parts of the left middle frontal gyrus, superior parietal lobule, and precuneus, and reduced white matter volume in the left parietal lobe. To conclude, our behavioral findings reveal that processing speed is differentially impacted across the three PPA variants and provide support for the potential clinical utility of a tabled-based task (Match) to assess non-verbal cognition. In addition, our neuroimaging findings confirm the importance of a set of fronto-parietal regions that previous research has associated with processing speed and executive control. Finally, our behavioral and neuroimaging findings combined indicate that differences in processing speed are largely explained by the unequal distribution of atrophy in these fronto-parietal regions across the three PPA variants.

Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease.

Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases. Our analysis included 117 participants with dominantly inherited Alzheimer's disease enrolled in the Dominantly Inherited Alzheimer Network and 118 individuals with sporadic early-onset Alzheimer's disease enrolled at the University of California San Francisco Alzheimer's Disease Research Center. Baseline differences in clinical and biomarker profiles between both groups were compared using t-tests. Differences in the rates of decline were compared using linear mixed-effects models. Individuals with dominantly inherited Alzheimer's disease exhibited an earlier age-at-symptom onset compared with the sporadic group [43.4 (SD ± 8.5) years versus 54.8 (SD ± 5.0) years, respectively, P < 0.001]. Sporadic cases showed a higher frequency of atypical clinical presentations relative to dominantly inherited (56.8% versus 8.5%, respectively) and a higher frequency of APOE-ε4 (50.0% versus 28.2%, P = 0.001). Compared with sporadic early onset, motor manifestations were higher in the dominantly inherited cohort [32.5% versus 16.9% at baseline (P = 0.006) and 46.1% versus 25.4% at last visit (P = 0.001)]. At baseline, the sporadic early-onset group performed worse on category fluency (P < 0.001), Trail Making Test Part B (P < 0.001) and digit span (P < 0.001). Longitudinally, both groups demonstrated similar rates of cognitive and functional decline in the early stages. After 10 years from symptom onset, dominantly inherited participants experienced a greater decline as measured by Clinical Dementia Rating Sum of Boxes [3.63 versus 1.82 points (P = 0.035)]. CSF amyloid beta-42 levels were comparable [244 (SD ± 39.3) pg/ml dominantly inherited versus 296 (SD ± 24.8) pg/ml sporadic early onset, P = 0.06]. CSF phosphorylated tau at threonine 181 levels were higher in the dominantly inherited Alzheimer's disease cohort (87.3 versus 59.7 pg/ml, P = 0.005), but no significant differences were found for t-tau levels (P = 0.35). In summary, sporadic and inherited Alzheimer's disease differed in baseline profiles; sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline. Despite these differences, shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations, offering valuable insights for future research and clinical trial design.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

A novel approach for the detection of cognitive impairment and delirium risk in older patients undergoing spine surgery.

BACKGROUND: Postoperative delirium is a common postsurgical complication in older patients and is associated with high morbidity and mortality. The objective of this study was to determine whether a digital cognitive assessment and patient characteristics could identify those at-risk. METHODS: Patients 65 years and older undergoing spine surgeries ≥3 h were evaluated as part of a single-center prospective observational cohort study at an academic medical center, from January 1, 2019, to December 31, 2020. Of 220 eligible patients, 161 were enrolled and 152 completed the study. The primary outcome of postoperative delirium was measured by the Confusion Assessment Method for the Intensive Care Unit or the Nursing Delirium Screening Scale, administered by trained nursing staff independent from the study protocol. Baseline cognitive impairment was identified using the tablet-based TabCAT Brain Health Assessment. RESULTS: Of the 152 patients included in this study, 46% were women. The mean [SD] age was 72 [5.4] years. Baseline cognitive impairment was identified in 38% of participants, and 26% had postoperative delirium. In multivariable analysis, impaired Brain Health Assessment Cognitive Score (OR 2.45; 95% CI, 1.05-5.67; p = 0.037), depression (OR 4.54; 95% CI, 1.73-11.89; p = 0.002), and higher surgical complexity Tier 4 (OR 5.88; 95% CI, 1.55-22.26; p = 0.009) were associated with postoperative delirium. The multivariate model was 72% accurate for predicting postoperative delirium, compared to 45% for the electronic medical record-based risk stratification model currently in use. CONCLUSION: In this prospective cohort study of spine surgery patients, age, cognitive impairment, depression, and surgical complexity identified patients at high risk for postoperative delirium. Integration of scalable digital assessments into preoperative workflows could identify high-risk patients, automate decision support for timely interventions that can improve patient outcomes and lower hospital costs, and provide a baseline cognitive assessment to monitor for postoperative cognitive change.

Feasibility and Acceptability of a Multidisciplinary Academic Telemedicine System for Memory Care in Response to COVID-19.

Background and Objectives: In response to the restrictions imposed by the COVID-19 pandemic, the University of California San Francisco Memory and Aging Center (UCSF MAC) has deployed a comprehensive telemedicine model for the diagnosis and management of Alzheimer disease and related dementias. This review summarizes a large academic behavioral neurology clinic's experience transitioning to telemedicine services, including the impact on clinic care indicators, access metrics, and provider's experience. We compared these outcomes from 3 years before COVID-19 to 12 months after the transition to video teleconferencing (VTC) encounters. Methods: Patient demographics and appointment data (dates, visit types, and departments) were extracted from our institution's electronic health record database from January 1, 2017, to May 1, 2021. We present data as descriptive statistics and comparisons using Wilcoxon rank-sum tests and Fisher exact tests. The results of anonymous surveys conducted among the clinic's providers are reported as descriptive findings. Results: After the implementation of telemedicine services, the proportion of clinic encounters completed via VTC increased from 1.9% to 86.4%. There was a statistically significant decline in both the percentage of scheduled appointments that were canceled (32.9% vs 27.9%; p < 0.01) and total cancelations per month (mean 240.3 vs 179.4/mo; p < 0.01). There was an increase in the percentage of completed scheduled appointments (60.2% vs 64.8%; p < 0.01) and an increase in the average estimated commuting distance patients would need to drive for follow-up appointments (mean 49.8 vs 54.7 miles; p < 0.01). The transition to telemedicine services did not significantly affect the clinic's patient population as measured by age, gender, estimated income, area deprivation index, or self-reported racial/ethnic identity. The results of the provider survey revealed that physicians reported a more positive experience relative to neuropsychologists. Both types of providers reported telemedicine services as a reasonable equivalent and acceptable alternative to in-person evaluations with notable caveats. Discussion: UCSF MAC's comprehensive integration of telemedicine services maintained critical ambulatory care to patients living with dementia during the COVID-19 pandemic. The recognized benefits of our care model suggest dementia telemedicine may be used as a feasible and equivalent alternative to in-person ambulatory care in the after COVID-19 era.

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.

Facilitators and Barriers to Dementia Assessment and Diagnosis: Perspectives From Dementia Experts Within a Global Health Context.

Objectives: Dementia poses one of the greatest global health challenges, affecting 50 million people worldwide. With 10 million new cases each year, dementia is a growing burden, particularly in low- and middle-income countries (LMIC). This study aimed to identify the facilitators and barriers to providing quality dementia assessment and care in LMICs from a global health perspective. Methods/Design: A qualitative semi-structured interview study with 20 dementia expert healthcare providers from 19 countries. To be included, providers had to: practice dementia assessment or care in LMICs where the population over age 60 is projected to more than double by 2050 and be recognized as a leading dementia expert in the region based on position, research publications, and/or policy leadership. Interviews were analyzed by a multidisciplinary team of researchers using thematic analysis. Results: Barriers to dementia assessment and care included stigma about dementia, poor patient engagement in and access to healthcare, inadequate linguistic and cultural validation, limited dementia capable workforce, competing healthcare system priorities, and insufficient health financing. Facilitators included the rise in dementia awareness campaigns, dementia training for general practitioners, availability of family support and family caregivers, and national and international collaborations including coordinated policy efforts and involvement in international research initiatives. Conclusions: Findings from this study provide insights for prioritizing dementia assessment and care capacity-building in LMICs as a global health priority and for tailored public health approaches to strengthen dementia assessment and care at the individual, community, national, and multi-national levels.

Lessons from Detecting Cognitive Impairment Including Dementia (DetectCID) in Primary Care.

BACKGROUND: Cognitive impairment, including dementia, is frequently under-detected in primary care. The Consortium for Detecting Cognitive Impairment, including Dementia (DetectCID) convenes three multidisciplinary teams that are testing novel paradigms to improve the frequency and quality of patient evaluations for detecting cognitive impairment in primary care and appropriate follow-up. OBJECTIVE: Our objective was to characterize the three paradigms, including similarities and differences, and to identify common key lessons from implementation. METHODS: A qualitative evaluation study with dementia specialists who were implementing the detection paradigms. Data was analyzed using content analysis. RESULTS: We identified core components of each paradigm. Key lessons emphasized the importance of engaging primary care teams, enabling primary care providers to diagnose cognitive disorders and provide ongoing care support, integrating with the electronic health record, and ensuring that paradigms address the needs of diverse populations. CONCLUSION: Approaches are needed that address the arc of care from identifying a concern to post-diagnostic management, are efficient and adaptable to primary care workflows, and address a diverse aging population. Our work highlights approaches to partnering with primary care that could be useful across specialties and paves the way for developing future paradigms that improve differential diagnosis of symptomatic cognitive impairment, identifying not only its presence but also its specific syndrome or etiology.

Global Perspectives on Brief Cognitive Assessments for Dementia Diagnosis.

BACKGROUND: Timely diagnosis of dementia is a global healthcare priority, particularly in low to middle income countries where rapid increases in older adult populations are expected. OBJECTIVE: To investigate global perspectives on the role of brief cognitive assessments (BCAs) in dementia diagnosis, strengths and limitations of existing measures, and future directions and needs. METHODS: This is a qualitative study of 18 dementia experts from different areas of the world. Participants were selected using purposeful sampling based on the following criteria: 1) practicing in countries with projected growth of older adult population of over 100%by 2050; 2) expertise in dementia diagnosis and treatment; 3) involvement in clinical practice and training; and 4) recognition as a national dementia expert based on leadership positions within healthcare system, research, and/or policy work. Participants were individually interviewed in their language of choice over secure videoconference sessions. Interviews were analyzed by a multidisciplinary team using theme identification approach. RESULTS: Four domains with subthemes emerged illustrating participants' perspectives: 1) strengths of BCAs; 2) limitations of BCAs; 3) needs related to the use of BCAs; and 4) characteristics of an ideal BCA. While most experts agreed that BCAs were important and useful for dementia diagnosis, the themes emphasized the need for development and validation of novel measures that are sensitive, psychometrically sound, and culturally appropriate. CONCLUSION: BCAs are important for guiding diagnosis and care for dementia patients. Findings provide a roadmap for novel BCA development to assist in diagnostic decision making for clinicians serving a rapidly growing and diverse dementia population.

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.

Detecting Alzheimer's disease biomarkers with a brief tablet-based cognitive battery: sensitivity to Aß and tau PET.

BACKGROUND: ß-amyloid (Aß) and tau positron emission tomography (PET) detect the pathological changes that define Alzheimer's disease (AD) in living people. Cognitive measures sensitive to Aß and tau burden may help streamline identification of cases for confirmatory AD biomarker testing. METHODS: We examined the association of Brain Health Assessment (BHA) tablet-based cognitive measures with dichotomized Aß -PET status using logistic regression models in individuals with mild cognitive impairment (MCI) or dementia (N = 140; 43 Aß-, 97 Aß+). We also investigated the relationship between the BHA tests and regional patterns of tau-PET signal using voxel-wise regression analyses in a subsample of 60 Aß+ individuals with MCI or dementia. RESULTS: Favorites (associative memory), Match (executive functions and speed), and Everyday Cognition Scale scores were significantly associated with Aß positivity (area under the curve [AUC] = 0.75 [95% CI 0.66-0.85]). We found significant associations with tau-PET signal in mesial temporal regions for Favorites, frontoparietal regions for Match, and occipitoparietal regions for Line Orientation (visuospatial skills) in a subsample of individuals with MCI and dementia. CONCLUSION: The BHA measures are significantly associated with both Aß and regional tau in vivo imaging markers and could be used for the identification of patients with suspected AD pathology in clinical practice.

Worth the Wait: Delayed Recall after 1 Week Predicts Cognitive and Medial Temporal Lobe Trajectories in Older Adults.

METHOD: Clinically normal older adults (52-92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178-207, mean ages = 74-76) at annual study visits occurring approximately 15-18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics. RESULTS: Worse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044). CONCLUSIONS: Memory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories. (JINS, 2020, xx, xx-xx).

A Brief Digital Cognitive Assessment for Detection of Cognitive Impairment in Cuban Older Adults.

BACKGROUND: Rapid technological advances offer a possibility to develop cost-effective digital cognitive assessment tools. However, it is unclear whether these measures are suitable for application in populations from Low and middle-income countries (LMIC). OBJECTIVE: To examine the accuracy and validity of the Brain Health Assessment (BHA) in detecting cognitive impairment in a Cuban population. METHODS: In this cross-sectional study, 146 participants (cognitively healthy = 53, mild cognitive impairment (MCI) = 46, dementia = 47) were recruited at primary care and tertiary clinics. The main outcomes included: accuracy of the BHA and the Montreal Cognitive Assessment (MoCA) in discriminating between controls and cognitively impaired groups (MCI and dementia) and correlations between the BHA subtests of memory, executive functions, and visuospatial skills and criterion-standard paper-and-pencil tests in the same domains. RESULTS: The BHA had an AUC of 0.95 (95% CI: 0.91-0.98) in discriminating between controls and cognitively impaired groups (MCI and dementia, combined) with 0.91 sensitivity at 0.85 specificity. In discriminating between control and MCI groups only, the BHA tests had an AUC of 0.94 (95% CI: 0.90-0.99) with 0.71 sensitivity at 0.85 specificity. Performance was superior to the MoCA across all diagnostic groups. Concurrent and discriminant validity analyses showed moderate to strong correlations between the BHA tests and standard paper-and-pencil measures in the same domain and weak correlations with standard measures in unrelated domains. CONCLUSION: The BHA has excellent performance characteristics in detecting cognitive impairment including dementia and MCI in a Hispanic population in Cuba and outperformed the MoCA. These results support potential application of digital cognitive assessment for older adults in LMIC.

Symptomatic amyloid-related imaging abnormalities in an APOE ε4/ε4 patient treated with aducanumab.

INTRODUCTION: Amyloid-related imaging abnormalities (ARIA) are a common, dose-dependent effect of amyloid-targeting antibodies, strongly associated with the apolipoprotein E (APOE) ε4 allele. METHODS: We describe the clinical course and management of a 66-year-old white male (APOE ε4/ε4) enrolled in an observational study that included amyloid and tau positron emission tomography (PET), who received aducanumab through the ENGAGE clinical trial. RESULTS: Acute symptoms included headache and encephalopathy, and magnetic resonance imaging revealed ARIA-E and ARIA-H. Malignant hypertension and epileptiform activity were treated with nicardipine and levetiracetam. Subsequent clinical/imaging worsening prompted a course of methylprednisolone. Symptoms and ARIA-E resolved over 6 months, while ARIA-H persisted. Quantitative analysis of interval amyloid PET showed reduced signal in pre-existing areas but increased signal posteriorly; while tau PET showed increased signal overall. DISCUSSION: In an APOE ε4/ε4 patient, ARIA symptoms were accompanied by malignant hypertension and epileptiform activity, and pulsed steroids reversed edema. Studies from larger cohorts may clarify the optimal treatment and pathophysiology of ARIA.

Sex-related differences in the relationship between ß-amyloid and cognitive trajectories in older adults.

Objective: We aimed to test the hypothesis that elevated neocortical ß-amyloid (Aß), a hallmark feature of Alzheimer's disease (AD), predicts sex-specific cognitive trajectories in clinically normal older adults, with women showing greater risk of decline than men. Method: Florbetapir Aß positron emission tomography (PET) was acquired in 149 clinically normal older adults (52% female, Mage = 74). Participants underwent cognitive testing at baseline and during annual follow-up visits over a timespan of up to 5.14 years. Mixed-effects regression models evaluated whether relations between baseline neocortical Standardized Uptake Value Ratio (SUVR) and composite scores of episodic memory, executive functioning, and processing speed were moderated by sex (male/female) and apolipoprotein E (APOE) status (ε4 carrier/noncarrier). Results: Higher baseline SUVR was associated with longitudinal decline in episodic memory in women (b = -1.32, p < .001) but not men (b = -0.30, p = .28). Female APOE ε4 carriers with elevated SUVR showed particularly precipitous declines in episodic memory (b = -4.33, p < .001) whereas other cognitive domains were spared. SUVR did not predict changes in executive functioning or processing speed, regardless of sex (ps >.63), though there was a main effect of SUVR on processing speed (b = 2.50, p = .003). Conclusions: Clinically normal women with elevated Aß are more vulnerable to episodic memory decline than men. Understanding sex-related differences in AD, particularly in preclinical stages, is crucial for guiding precision medicine approaches to early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).