Neuropsychiatric Symptom Profile in Alzheimer's Disease and Their Relationship With Functional Decline.

OBJECTIVE: Understanding the course of individual neuropsychiatric symptoms (NPS) and their relationship with function is important for planning targeted interventions for preventing and delaying functional decline. This study aims to disentangle relative contributions of individual NPS on functional decline. METHODS: Longitudinal study of 9,358 well-characterized participants with baseline diagnoses of Mild Cognitive Impairment or AD in the National Alzheimer's Coordinating Center Uniform Data Set. Function was measured using the Functional Assessment Questionnaire (FAQ). Clinician judgment of seven common behavioral symptoms were examined simultaneously: apathy-withdrawal, depressed mood, visual or auditory hallucinations, delusions, disinhibition, irritability, and agitation. RESULTS: Apathy was the most common NPS at baseline (33.7%) and throughout follow-up, endorsed by clinicians in 63.7% of visits. Apathy was the most persistent with 36.7% of participants having clinician-endorsed apathy in ≥50% of their visits. Apathy strongly correlated with faster rate of functional decline. Compared to those who never had apathy, baseline FAQ was worse in those with intermittent or persistent/always apathy (intermittent: estimated coefficient ±SE=1.228±0.210, 95% CI=[0.817, 1.639]; persistent/always: 2.354±0.244 (95% CI=[1.876, 2.832], both p <0.001). Over time, rate of functional decline was faster in those with intermittent and persistent/always apathy (intermittent: 0.454±0.091, 95% CI=[0.276, 0.632]; persistent/always: 0.635±0.102, 95% CI=[0.436, 0.835], both p <0.001). Worse agitation, delusions, and hallucinations also correlated with functional decline, but magnitudes of the estimates were smaller. CONCLUSION: Individual NPS may be sensitive targets for tracking longitudinal change in function. The study raises awareness of the need for more comprehensive assessment of functional decline in AD patients with noncognitive symptoms.

Lessons From the Coronavirus Disease Experience: Research Participant and Staff Satisfaction With Remote Cognitive Evaluations.

OBJECTIVE: In New York City in 2020 the pandemic shut down in-person research. Icahn School of Medicine's Alzheimer's Disease Research Center transitioned longitudinal evaluations from in-person to telephone to enhance equity of access. We assessed diverse research participants' and clinical research coordinators' (CRC) satisfaction with remote evaluation and examined sociodemographic, cognitive, and behavioral factors that might impact satisfaction. METHODS: Data collected: 241 participants with Clinical Dementia Rating (CDR) = 0/0.5 (3/2020 to 6/2021). A Telehealth Satisfaction Questionnaire for CRCs and participants was administered at the end of remote evaluations. We compared Telehealth Satisfaction Questionnaire items by CDR and Geriatric Depression Scale. RESULTS: Participants' mean age was 78.4, 61.4% were females, 16.2% were Hispanic, 17.1% Asian, 15.8% were non-Hispanic black, and 72.6% CDR = 0. Participant satisfaction was high [14.1 ± 1.4 (out of 15)] but was lower among those with depression. CRC satisfaction was high [16.9 ± 1.8 (out of 18)] but was lower concerning the ability to explain the test battery and interact with participants with CDR = 0.5. CONCLUSION: Telephone research assessments provide flexibility in a hybrid model. They offer equitable access to research participation for those who do not use computer technology and may promote the retention of diverse elderly research participants.

INviting Veterans InTo Enrollment in Alzheimer's Disease Research Centers (INVITE-ADRC): An NIA and VA-sponsored initiative to increase veteran participation in aging and dementia research.

INTRODUCTION: Older military veterans often present with unique and complex risk factors for Alzheimer's disease (AD) and related dementias. Increasing veteran participation in research studies offers one avenue to advance the field and improve health outcomes. METHODS: To this end, the National Institute on Aging (NIA) and Department of Veterans Affairs (VA) partnered to build infrastructure, improve collaboration, and intensify targeted recruitment of veterans. This initiative, INviting Veterans InTo Enrollment in Alzheimer's Disease Research Centers (INVITE-ADRC), provided funding for five sites and cross-site organizing structure. Diverse and innovative recruitment strategies were used. RESULTS: Across five sites, 172 veterans entered registries, and 99 were enrolled into ADRC studies. Of the enrolled, 39 were veterans from historically underrepresented racial and ethnic groups. CONCLUSIONS: This initiative laid the groundwork to establish sustainable relationships between the VA and ADRCs. The partnership between both federal agencies demonstrates how mutual interests can accelerate progress. In turn, efforts can help our aging veterans.

The Neurovascular Unit as a Locus of Injury in Low-Level Blast-Induced Neurotrauma.

Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood-brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury.

Meaningful benefit of disease-modifying treatment: Evaluating changes in health-related resource use.

INTRODUCTION: Are reductions in the rate of decline from the new disease-modifying treatments (DMTs) in early Alzheimer's disease (AD) meaningful? We examined whether such reductions may be reflected in changes in health-related resource use. METHODS: Patients with Clinical Dementia Rating (CDR) = 0.5 or 1 with a clinical diagnosis of mild cognitive impairment or AD, reflecting clinical trial populations. Health-related resource use was reported using the Resource Use Inventory (RUI) including direct medical care, non-medical care, unpaid informal care, and time use. RESULTS: Faster decline in CDR-Sum of Boxes (CDR-SB) from baseline was independently associated with higher likelihood and hours of informal care received, and lower likelihood of employment/volunteer work, but not with direct medical care. DISCUSSION: Reductions in the rate of decline in CDR-SB seen from DMTs significantly affect patients' work capacity and need for informal care, indicators of economic impact meaningful to patients, families, and health systems. These measures are not readily captured in administrative data sets. Highlights: Following a cohort of participants with MCI or mild dementia due to AD that mimics participants targeted for AD trials, this study showed slower decline in CDR-SB have significant effects on patients' work capacity and need for informal care, but not on their direct medical care utilization such as hospitalizations, ED use, and doctors' visits.Capturing potential benefits in health-related resource use may require direct measures of informal care and work/volunteer effort which are meaningful outcomes to patients, families and health systems.Caution is needed in our effort to assess benefits of recently developed disease modifying treatment in AD using electronic health records and administrative data from which utilization of direct medical care are routinely collected as these data sources may not capture the most apparent changes in resource utilization during early disease stages.

Apathy in Lewy body disease and its effects on functional impairment over time.

Background and objectives: Apathy strongly affects function in Alzheimer's disease and frontotemporal dementia, however its effect on function in Lewy Body Disease (LBD) has not been well-described. This study aims to (1) examine the prevalence and persistence of apathy in a large, national cohort of well-characterized patients with LBD, and (2) estimate the effect of apathy on function over time. Methods: Study included 676 participants with mild cognitive impairment (MCI) or dementia in the National Alzheimer's Coordinating Center Uniform Data Set. Participants were followed for an average of 3.4 ± 1.7 years and consistently had a primary diagnosis of LBD. Apathy was defined by clinician judgment, categorized into four mutually exclusive profiles: (1) never apathetic across all visits, (2) at least one but <50% of visits with apathy (intermittent apathy), (3) ≥50% but not all visits with apathy (persistent apathy), and (4) always apathy across all visits. Dementia severity was measured by baseline Clinical Dementia Rating score. Parkinsonism was defined by the presence of bradykinesia, resting tremor, rigidity, gait, and postural instability. Functional impairment was assessed using the Functional Assessment Questionnaire (FAQ). Results: Baseline characteristics of the sample were: average age = 72.9 ± 6.9, years of education = 15.6 ± 3.4, Mini Mental State Exam (MMSE) = 24.4 ± 5.4, Geriatric Depression Scale (GDS) = 3.8 ± 3.2, FAQ = 12.0 ± 9.1. 78.8% were male and 89% were non-Hispanic white. Prevalence of apathy increased from 54.4% at baseline to 65.5% in year 4. 77% of participants had apathy at some point during follow-up. Independent of cognitive status and parkinsonian features, FAQ was significantly higher in participants with intermittent/persistent and always apathetic than never apathetic. Annual rate of decline in FAQ was faster in participants who were always apathetic than never apathy. Discussion: In this large national longitudinal cohort of LBD patients with cognitive impairment, apathy was strongly associated with greater functional impairment at baseline and faster rate of decline over time. The magnitude of these effects were clinically important and were observed beyond the effects on function from participants' cognitive status and parkinsonism, highlighting the importance of specifically assessing for apathy in LBD.