Recruitment Barriers and Potential Strategies for Inclusion of Older Asian Americans in Alzheimer's Disease Research.

The makeup of the US population of older adults continues to become more diverse as numbers from ethnic subgroups increase. However, these subgroups are generally underrepresented in research focused on Alzheimer's disease and related dementias (ADRD). This paper examines barriers to recruitment for older Asian Americans, to underpin potential strategies for future research, with particular emphasis on recruitment of Vietnamese Americans. The paper discusses three recommended strategies: implementing appropriate recruitment outreach methods, establishing and maintaining community partnerships, and adopting flexible and convenient assessment methods. All three complementary approaches may be applied to improve Vietnamese American aging research participation. This has the potential to promote early intervention, foster longevity, ameliorate health disparities, and reduce healthcare burdens for this population.

Can't Have One Without the Other: Study Partner Retention in Alzheimer's Disease Research.

Alzheimer's disease (AD) clinical research depends on engaging and enrolling appropriate research participants to address specific scientific questions. Investigators, however, are beginning to recognize the importance of participant study partners who contribute to AD research in multiple ways, including their contributions to the diagnostic process through observations of participant cognition and daily functioning. These contributions justify increased efforts to understand factors that impede or facilitate their willingness to remain in this role in longitudinal studies and clinical trials. Study partners, including those from diverse, underrepresented communities, are stakeholders significantly invested in AD research that benefits all living with the disease.

Comparison of the telephone-Montreal Cognitive Assessment (T-MoCA) and Telephone Interview for Cognitive Status (TICS) as screening tests for early Alzheimer's disease.

INTRODUCTION: Remote screening for cognitive impairment associated with Alzheimer's disease (AD) has grown in importance with the expected rise in prevalence of AD in an aging population and with new potential treatment options. METHODS: The Telephone Interview for Cognitive Status (TICS) and new telephone adaptation of the Montreal Cognitive Assessment (T-MoCA) were administered to participants independently classified through in-person clinical evaluation as cognitively normal (CN; n = 167), mild cognitive impairment (MCI; n = 25), or dementia (n = 23). Cerebrospinal fluid AD biomarkers were measured (n = 79). RESULTS: TICS and T-MoCA were highly correlated (r = 0.787; P < 0.001): groups differed on both (CN

Association of Neurofibrillary Tangle Distribution With Age at Onset-Related Clinical Heterogeneity in Alzheimer Disease: An Autopsy Study.

BACKGROUND AND OBJECTIVE: Patients with earlier age at onset of sporadic Alzheimer disease (AD) are more likely than those with later onset to present with atypical clinical and cognitive features. We sought to determine whether this age-related clinical and cognitive heterogeneity is mediated by different topographic distributions of tau-aggregate neurofibrillary tangles (NFTs) or by variable amounts of concomitant non-AD neuropathology. METHODS: The relative distribution of NFT density in hippocampus and midfrontal neocortex was calculated, and α-synuclein, TAR DNA binding protein 43 (TDP-43), and microvascular copathologies were staged, in patients with severe AD and age at onset of 51-60 (n = 40), 61-70 (n = 41), and >70 (n = 40) years. Regression, mediation, and mixed effects models examined relationships of pathologic findings with clinical features and longitudinal cognitive decline. RESULTS: Patients with later age at onset of AD were less likely to present with nonmemory complaints (odds ratio [OR] 0.46 per decade, 95% confidence interval [CI] 0.22-0.88), psychiatric symptoms (ß = -0.66, 95% CI -1.15 to -0.17), and functional impairment (ß = -1.25, 95% CI -2.34 to -0.16). TDP-43 (OR 2.00, 95% CI 1.23-3.35) and microvascular copathology (OR 2.02, 95% CI 1.24-3.40) were more common in later onset AD, and α-synuclein copathology was not related to age at onset. NFT density in midfrontal cortex (ß = -0.51, 95% CI -0.72 to -0.31) and midfrontal/hippocampal NFT ratio (ß = -0.18, 95% CI -0.26 to -0.10) were lower in those with later age at onset. Executive function (ß = 0.48, 95% CI 0.09-0.90) and visuospatial cognitive deficits (ß = 0.97, 95% CI 0.46-1.46) were less impaired in patients with later age at onset. Mediation analyses showed that the effect of age at onset on severity of executive function deficits was mediated by midfrontal/hippocampal NFT ratio (ß = 0.21, 95% CI 0.08-0.38) and not by concomitant non-AD pathologies. Midfrontal/hippocampal NFT ratio also mediated an association between earlier age at onset and faster decline on tests of global cognition, executive function, and visuospatial abilities. DISCUSSION: Worse executive dysfunction and faster cognitive decline in people with sporadic AD with earlier rather than later age at onset is mediated by greater relative midfrontal neocortical to hippocampal NFT burden and not by concomitant non-AD neuropathology.

A survey of smartphone and interactive video technology use by participants in Alzheimer's disease research: Implications for remote cognitive assessment.

INTRODUCTION: Participants from a longitudinal cohort study were surveyed to evaluate the practical feasibility of remote cognitive assessment. METHODS: All active participants/informants at the University of California San Diego Alzheimer's Disease Research Center were invited to complete a nine-question survey assessing technology access/use and willingness to do cognitive testing remotely. RESULTS: Three hundred sixty-nine of 450 potential participants/informants (82%) completed the survey. Overall, internet access (88%), device ownership (77%), and willingness to do cognitive testing remotely (72%) were high. Device access was higher among those with normal cognition (85%) or cognitive impairment (85%) than those with dementia (52%), as was willingness to do remote cognitive testing (84%, 74%, 39%, respectively). Latinos were less likely than non-Latinos to have internet or device access but were comparable in willingness to do remote testing. DISCUSSION: Remote cognitive assessment using interactive video technology is a practicable option for nondemented participants in longitudinal studies; however, additional resources will be required to ensure representative participation of Latinos.

Community memory screening as a strategy for recruiting older adults into Alzheimer's disease research.

BACKGROUND: Growing awareness of Alzheimer's disease (AD) has prompted a demand for quick and effective ways to screen for memory loss and cognitive decline in large numbers of individuals in the community. Periodic Memory Screening Day events provide free, brief cognitive screening aimed at those 65 years and older, and can serve as an opportunity to gauge participants' attitudes towards AD research and recruit them into ongoing research projects. METHODS: Over 6 single-day events in 2 years, more than 574 individuals were individually screened using the MoCA and a story recall task (immediate and delayed), given feedback about their performance, and introduced to AD research and opportunities to participate. RESULTS: Screening classified 297 individuals (52.0%) as having "No Decline," 192 (33.6%) as "Possible decline," and 82 (14.4%) as "Likely decline." Those with "Likely decline" were older and less educated, had more memory concerns, were more likely to be men, and were less likely to have a positive family history of dementia than those with "No Decline." Subsequent validation of screening procedures against a full clinical evaluation showed 72% classification accuracy with a skew towards over-calling Possible and Likely decline and thereby guiding questionable individuals to a more thorough evaluation. Of those screened, 378 (66%) agreed to additional research and consented to being listed in a research registry, and a majority (70-85%) of those consenting reported they were amenable to various AD research procedures including lumbar puncture, MRI, and autopsy. Overall, 19.1% of those screened met inclusion criteria for ongoing studies and were successfully recruited into AD research. CONCLUSIONS: Conducting a few concentrated community memory screening events each year may help meet the public's demand for brief assessment of memory concerns and can be a relatively effective and efficient recruitment strategy for AD research.

Lay Caregivers' Experiences With Caring for Persons With Dementia: A Phenomenological Study.

Today, biomedical advancements allow older adults, including those with dementia, to live longer, with most living at home with a lay caregiver. Recent research details the stressful role of caregiving to persons with dementia (PWD). The current qualitative phenomenological study describes the lived experience of caregivers caring for PWD, including their experience with palliative care. A community sample of lay caregivers (N = 11) underwent recorded individual interviews. Interviews were analyzed following van Manen's approach to isolate thematic statements. Most caregivers were older (mean age = 71, SD = 9.6; range = 53 to 84 years) and female (n = 10). Study themes included: (a) Uncertainty: The Slippery Slope, (b) The Sense of Loneliness, (c) Complexities of Frustration, and (d) On the Other Side of the Spectrum. Findings show these caregivers are dealing with a dynamic range of feelings about their experiences. Opportunities exist for health care professionals to discuss such feelings and refer caregivers to supportive services, including palliative care. [Journal of Gerontological Nursing, 46(8), 17-27.].

Attitudes toward advance care planning among persons with dementia and their caregivers.

OBJECTIVES: To examine factors that influence decision-making, preferences, and plans related to advance care planning (ACP) and end-of-life care among persons with dementia and their caregivers, and examine how these may differ by race. DESIGN: Cross-sectional survey. SETTING: 13 geographically dispersed Alzheimer's Disease Centers across the United States. PARTICIPANTS: 431 racially diverse caregivers of persons with dementia. MEASUREMENTS: Survey on "Care Planning for Individuals with Dementia." RESULTS: The respondents were knowledgeable about dementia and hospice care, indicated the person with dementia would want comfort care at the end stage of illness, and reported high levels of both legal ACP (e.g., living will; 87%) and informal ACP discussions (79%) for the person with dementia. However, notable racial differences were present. Relative to white persons with dementia, African American persons with dementia were reported to have a lower preference for comfort care (81% vs. 58%) and lower rates of completion of legal ACP (89% vs. 73%). Racial differences in ACP and care preferences were also reflected in geographic differences. Additionally, African American study partners had a lower level of knowledge about dementia and reported a greater influence of religious/spiritual beliefs on the desired types of medical treatments. Notably, all respondents indicated that more information about the stages of dementia and end-of-life health care options would be helpful. CONCLUSIONS: Educational programs may be useful in reducing racial differences in attitudes towards ACP. These programs could focus on the clinical course of dementia and issues related to end-of-life care, including the importance of ACP.

Associations among Braak stage, Parkinsonian gait, cognition, and functional status in autopsy-confirmed dementia with Lewy bodies.

OBJECTIVE: Compromised functional abilities in older adults with dementia with Lewy bodies (DLB) represent a significant burden to families and frequently lead to institutionalization. Contributing factors to this compromise are poorly understood. METHODS: Using data collected at a first study visit, multiple regression modeling was used to examine the associations between Braak staged Alzheimer disease (AD) pathology, Apolipoprotein E (ApoE) status, Parkinsonian gait, cognition, and functional status from a cohort of 102 cases with an autopsy-confirmed diagnosis of dementia stemming from combined Lewy body and AD pathology. RESULTS: On average, 60% of functional activities were compromised per case. Worse functional status was associated with older age at first study visit, compromised cognitive status, and Parkinsonian gait after controlling for gender, mental status, and other covariates. Worse cognitive status predicted worse functional status in both the low and high Braak groups. CONCLUSIONS: Older persons with DLB presenting with moderately compromised cognition and Parkinsonian gait should be expected to have impaired functional abilities. Providing these patients with supportive environments may help them to remain independent for longer periods of time.

Clinical-Neuropathological Correlations of Alzheimer's Disease and Related Dementias in Latino Volunteers.

Clinical, neuropsychological, and neurological procedures used to diagnose Alzheimer's disease (AD) and related dementias were largely developed and validated in well-educated, non-Latino, English-speaking populations. Sociocultural and genetic differences in Latinos might influence the accuracy of clinical diagnosis of AD and other dementias. We aim to compare the accuracy of the clinical diagnosis of AD and related dementias in Latinos with the corresponding neuropathological diagnosis. From the UCSD Alzheimer's Disease Research Center longitudinal cohort, we selected all Latino participants who had autopsy neuropathological studies from 1991 to 2017. Participants underwent annual neurological clinical evaluations, standard neuropsychological tests, neuroimaging, and genotyping of Apolipoprotein E. We calculated the sensitivity and specificity of the clinical diagnosis of AD against the primary pathological diagnosis. Of the 34 participants with a primary neuropathological diagnosis of AD, 33 (97.1%) were correctly clinically diagnosed as having AD at the last clinical evaluation, and 1 was incorrectly diagnosed with dementia with Lewy bodies. Of the 19 participants without a primary neuropathological diagnosis of AD, 8 were incorrectly clinically diagnosed with probable AD at the last clinic evaluation. The clinical diagnosis of AD at the last clinical evaluation had 97.1% sensitivity and 57.9% specificity for autopsy-verified AD. In this Latino cohort, clinicians predicted AD pathological findings with high sensitivity but moderate specificity. Tangle-only dementia was the most common misdiagnosis. Our study suggests that current procedures and instruments to clinically determine AD in Latinos have high sensitivity compared with neuropathology, but specificity needs to be improved.

The MoCA-Memory Index Score: An Efficient Alternative to Paragraph Recall for the Detection of Amnestic Mild Cognitive Impairment.

OBJECTIVE: To compare ability of 2 measures of delayed memory (word list, story paragraph) to discriminate Normal Control (NC) subjects from those with amnestic mild cognitive impairment (aMCI). METHODS: Demographic, neuropsychological, and diagnostic data contributed by 34 Alzheimer's Disease Centers to the National Alzheimer's Coordinating Center characterized 2717 individuals with a diagnosis of either NC (n=2205) or aMCI (n=512). The Montreal Cognitive Assessment-Memory Index Score (MoCA-MIS) assessed delayed word recall, and the Craft Story 21, delayed story recall. Logistic regression and receiver operator characteristic curves controlling for age, sex, and education assessed the ability of each test to differentiate NCs from subjects with aMCI. RESULTS: The MoCA-MIS had significantly better sensitivity and specificity (area under the receiver operator characteristic curve 0.83 vs. 0.80, P=0.004). At sensitivity 80%, the specificity of the MoCA-MIS was 69.1%, compared with 62.8% for the Craft Story. CONCLUSIONS: These data suggest that the MoCA-MIS, a recall score from items within the MoCA, is better at discriminating NCs from subjects with aMCI than the Craft Story. Word recall may be an efficient alternative to paragraph recall for diagnostic screening within clinical practice and research settings.

Phenotypic differences based on staging of Alzheimer's neuropathology in autopsy-confirmed dementia with Lewy bodies.

INTRODUCTION: The goal was to compare subgroups of dementia with Lewy Bodies (DLB) using neuropathological measures to differentiate 'pure' Lewy body (LB) dementia from 'mixed' DLB [co-occurring LB and Alzheimer's disease (AD) pathology] to facilitate diagnostic decision-making and future development of interventions based on predicted type(s) of neuropathology. Studies comparing these groups are rare relative to those differentiating 'pure' AD and all-cause DLB, and are limited by insufficient sample size, brief cognitive batteries, and/or absence of autopsy confirmation. To address these limitations, we assessed cognition and other features in a large, autopsy-confirmed DLB sample using an extensive neuropsychological battery. METHODS: Subjects from an AD research center autopsy series satisfying DLB pathology criteria were divided by an AD neuropathology index into DLB-LB (Braak stage 0-3) (n = 38) and DLB-AD (Braak stage 4-6) (n = 41) and compared on baseline variables from chart reviews and standardized measures. RESULTS: DLB-LB subjects were more impaired on visuospatial constructions, visual conceptual reasoning, and speed of processing, but less impaired on verbal memory and confrontation naming. All-type hallucinations occurred more frequently in DLB-LB, while delusions were common in both groups. Groups were similar in education and age at onset, and in baseline age, dementia severity, and functional capacity. CONCLUSION: Salient findings included greater impairment on visual tasks and speed of processing and more frequent reports of all-type hallucinations in DLB-LB compared to DLB-AD. Relatively intact confrontation naming in DLB-LB and no differences in reported delusions were of note. Identifying differences in phenotypic features can improve prediction of underlying neuropathology.

Accounting for functional loss in Alzheimer's disease and dementia with Lewy bodies: beyond cognition.

BACKGROUND: The relative contributions of cognitive, motor, and behavioral deficits to the impairment of physical or instrumental activities of daily living (ADLs) may differ in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: Multiple linear regression analyses were used to identify the amount of variability in physical self-maintenance and instrumental ADL ratings predicted by cognitive, motor, and behavioral indices separately for patients with autopsy-diagnosed DLB (n = 39) or AD (n = 39). RESULTS: Motor dysfunction accounted for significant variance in physical ADLs in DLB (R(2) change = 0.17), whereas behavioral (R(2) change = 0.23) and motor dysfunction (R(2) change = 0.13) accounted for significant variance in AD. Motor (R(2) change = 0.32) and cognitive (R(2) change = 0.10) dysfunction accounted for significant variance in instrumental ADLs in DLB, whereas cognitive (R(2) change = 0.36) and behavioral (R(2) change = 0.12) dysfunction accounted for significant variance in AD. CONCLUSIONS: Cognitive, motor, and behavioral deficits contribute differently to ADL changes in DLB and AD. Thus, treatments designed to ameliorate a certain aspect of AD or DLB (e.g., cognitive dysfunction) may have a larger impact on everyday functioning in one disorder than the other.

Temporal sequence learning in healthy aging and amnestic mild cognitive impairment.

UNLABELLED: BACKGROUND/STUDY CONTEXT: Temporal sequence learning is a critical aspect of episodic memory that may be dependent on the temporal and frontal lobes. Because amnestic mild cognitive impairment (aMCI) and normal aging may result in changes within the temporal and frontal lobes, the present study investigated temporal sequence learning in patients with aMCI, cognitively normal older adults, and young adults. METHODS: On each trial of a temporal sequence task, circles appeared one at a time at the end of each arm of a computerized radial eight-arm maze. Participants were asked to reproduce the temporal sequence by placing numbered circles (1 to 8) on the arms of the eight-arm maze. Participants were presented with the same fixed sequence on each trial until the sequence was replicated without any errors, or until 15 trials were presented. RESULTS: Individuals with aMCI required significantly more trials to learn the temporal sequence compared with older adults (p < .05). Older adults required significantly more trials to learn the sequence than young adults (p < .05). Older adults and individuals with aMCI committed significantly more Trial 1 errors (p < .05) than young adults; however, there were no significant differences between the aMCI and older adult groups on Trial 1. CONCLUSION: The results suggest that temporal sequence learning deficits are detectable in aMCI. These deficits may disrupt a number of cognitive processes, such as episodic memory, that are important for the execution of daily activities. The results suggest that although temporal sequence learning declines with normal aging, this decline is greater in individuals who have a diagnosis of aMCI and are at higher risk for developing Alzheimer's disease.

Subjective memory complaints are associated with diurnal measures of salivary cortisol in cognitively intact older adults.

OBJECTIVE: To investigate the relationship between subjective memory complaints (SMC) and the stress hormone cortisol using diurnal measures in older, cognitively intact subjects. METHODS: This cross-sectional study conducted at a university research center included 64 volunteers (with or without SMC) with a mean age of 78.6 (±6.3) years and diagnosis of cognitively normal based on objective neuropsychological testing. Measures of diurnal salivary cortisol, depressive symptoms, episodic memory performance, level of anxiety, and apolipoprotein E (APOE) e4 allele status were obtained. RESULTS: In multivariate logistic regression analyses with SMC as outcome, averaged postpeak cortisol, the cortisol awakening response, and depressive symptoms were significant predictors, whereas gender, memory performance, anxiety, and APOE-e4 status were not. CONCLUSIONS: Significant associations between SMC and diurnal measures of cortisol in cognitively intact elderly suggest that hypothalamic-pituitary-adrenal axis dysfunction may contribute to early neuropathologic changes in older adults who complain of memory decline undetected on neuropsychological testing.

Neuropsychiatric features of frontal lobe dysfunction in autopsy-confirmed patients with lewy bodies and "pure" Alzheimer disease.

OBJECTIVE: To compare patients with autopsy-confirmed Alzheimer disease (AD) and dementia with Lewy bodies (DLB) on the frequency of behaviors related to frontal system dysfunction and the association of these behaviors with dementia severity. METHODS: We performed a cross-sectional survey of a longitudinal cohort at a university research center for AD on a volunteer sample of 19 DLB and 38 AD participants with autopsy-confirmed diagnoses, similar in age (DLB: 77.3, AD: 77.5), education (DLB: 15.2, AD: 14.7), and Mini-Mental State Examination (MMSE) score (DLB: 20.6, AD: 20.5), with impairment ranging from mild deficits to moderate dementia. The Frontal Systems Behavior Scale (FrSBe)-Family Rating Form assessing patient apathy, disinhibition, and executive dysfunction by a knowledgeable informant was used. RESULTS: A two-way analysis of variance with the FrSBe total as the dependent variable revealed a significant MMSE by diagnosis interaction (F(1,53) = 9.34, p = 0.004). Mean FrSBe total for AD patients showed significant impairment across the range of dementia severity, whereas it was relatively preserved for DLB patients in the early stage of disease. The interaction term showed the same pattern for the executive dysfunction (F(1,53) = 7.62, p = 0.008), disinhibition (F(1,53) = 4.90, p = 0.031), and apathy (F(1,53) = 9.77, p = 0.003) subscales. CONCLUSION: Although frontal behavioral symptoms in AD patients were present regardless of stage of dementia, DLB patients showed significant frontal dysfunction only in later stages. Results suggest that frontal subcortical circuits associated with behaviors assessed by the FrSBe are affected early in AD but not until later stages in DLB. Assessing specific behaviors related to frontal systems, coupled with stage of cognitive decline, may aid in clinical differentiation of AD and DLB.

Difficulty modifying a sustained motor response in prodromal Huntington's disease.

We investigated the nature of motor symptoms in the preclinical stage of Huntington's disease. Individuals with the CAG expanded repeat of Huntington's disease (prHD) and two control groups were tested on a task requiring a releasing movement (releasing a depressed button) followed by a ballistic movement (pressing a different button). Movement times were measured separately for releasing and ballistic movements. The mean reaction time of the prHD group was significantly longer when releasing a movement than that of the other groups. The groups, however, did not differ significantly on movement time for ballistic movements. Our results show that motor slowing is evident prior to the clinical diagnosis of Huntington's disease and may reflect difficulty in modifying a sustained motor program.