Examining Associations Between Smartphone Use and Clinical Severity in Frontotemporal Dementia: Proof-of-Concept Study.

Background: Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.

Demographics, Symptoms, Psychotropic Use, and Caregiver Distress in Patients With Early vs Late Onset Dementia.

Background: Understanding experiences and challenges faced by persons living with Early-Onset Dementia (EOD) compared to individuals diagnosed with Late-Onset Dementia (LOD) is important for the development of targeted interventions.

Objective: Describe differences in sociodemographic, neuropsychiatric behavioral symptoms, caregiver characteristics, and psychotropic use.

Design, Setting, Participants: Cross-sectional, retrospective study including 908 UCLA Alzheimer's Dementia Care Program participants (177 with EOD and 731 with LOD).

Jargonaphasia in logopenic variant primary progressive aphasia.

Background: Logopenic variant primary progressive aphasia (lvPPA), which is most commonly an early onset variant of Alzheimer's disease (AD), is a progressive impairment in word retrieval and language expression. Clinicians often misdiagnose these patients when they present with severely unintelligible speech consistent with jargonaphasia.

Methods: We reviewed all patients presenting to a behavioral neurology program over a 23-year period who met criteria for lvPPA after completion of an evaluation extending to positron emission tomography (PET) of the brain.

Can Speaking More Than One Language Help Prevent Alzheimer's Disease?

Alzheimer's disease (AD) is an age-related neurocognitive disorder that is epidemic in the elderly population. Currently, there are limited pharmacological interventions, and this has heightened the urgency to identify potential preventable or modifiable risk factors that promote resilience to the neuropathological effects of AD. The regular use of two or more languages is one such factor that may increases cognitive reserve through the long-standing executive control involved in managing multiple languages in the brain.

Sex and APOE ε4 carrier effects on atrophy, amyloid PET, and tau PET burden in early-onset Alzheimer's disease.

Introduction: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD).

Methods: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification.

White matter hyperintensities are higher among early-onset Alzheimer's disease participants than their cognitively normal and early-onset nonAD peers: Longitudinal Early-onset Alzheimer's Disease Study (LEADS).

Introduction: We compared white matter hyperintensities (WMHs) in early-onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early-onset amyloid-negative cognitively impaired (EOnonAD) groups in the Longitudinal Early-Onset Alzheimer's Disease Study.

Methods: We investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t-tests and analyses of covariance.

Culpability for offenses in frontotemporal dementia and other brain disorders.

The responsibility of persons with brain disorders who commit offenses may depend on how their disorders alter brain mechanisms for culpability. Criminal behavior can result from brain disorders that alter social cognition including a neuromoral system of intuitive moral emotions that are absolute (deontological) normative codes and that includes an emotion-mediated evaluation of intentionality. This neuromoral system has its hub in the ventromedial prefrontal cortex (VMPFC) with other frontal, anterior temporal-amygdalar, insular, and right temporoparietal connections.

Network Connectivity Alterations across the MAPT Mutation Clinical Spectrum.

Objective: Microtubule-associated protein tau (MAPT) mutations cause frontotemporal lobar degeneration, and novel biomarkers are urgently needed for early disease detection. We used task-free functional magnetic resonance imaging (fMRI) mapping, a promising biomarker, to analyze network connectivity in symptomatic and presymptomatic MAPT mutation carriers.

Methods: We compared cross-sectional fMRI data between 17 symptomatic and 39 presymptomatic carriers and 81 controls with (1) seed-based analyses to examine connectivity within networks associated with the 4 most common MAPT-associated clinical syndromes (ie, salience, corticobasal syndrome, progressive supranuclear palsy syndrome, and default mode networks) and (2) whole-brain connectivity analyses.

The Implications of Moral Neuroscience for Brain Disease: Review and Update.

The last 2 decades have seen an explosion of neuroscience research on morality, with significant implications for brain disease. Many studies have proposed a neuromorality based on intuitive sentiments or emotions aimed at maintaining collaborative social groups. These moral emotions are normative, deontological, and action based, with a rapid evaluation of intentionality.

Baseline neuropsychiatric symptoms and psychotropic medication use midway through data collection of the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort.

Introduction: We examined neuropsychiatric symptoms (NPS) and psychotropic medication use in a large sample of individuals with early-onset Alzheimer's disease (EOAD; onset 40-64 years) at the midway point of data collection for the Longitudinal Early-onset Alzheimer's Disease Study (LEADS).

Methods: Baseline NPS (Neuropsychiatric Inventory - Questionnaire; Geriatric Depression Scale) and psychotropic medication use from 282 participants enrolled in LEADS were compared across diagnostic groups - amyloid-positive EOAD (n = 212) and amyloid negative early-onset non-Alzheimer's disease (EOnonAD; n = 70).

Results: Affective behaviors were the most common NPS in EOAD at similar frequencies to EOnonAD.

Profiling baseline performance on the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort near the midpoint of data collection.

Objective: The Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point.

Methods: Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer's disease [EOnonAD; n = 70]).

Results: Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates.

Learning slopes in early-onset Alzheimer's disease.

Objective: Investigation of learning slopes in early-onset dementias has been limited. The current study aimed to highlight the sensitivity of learning slopes to discriminate disease severity in cognitively normal participants and those diagnosed with early-onset dementia with and without β-amyloid positivity METHOD: Data from 310 participants in the Longitudinal Early-Onset Alzheimer's Disease Study (aged 41 to 65) were used to calculate learning slope metrics. Learning slopes among diagnostic groups were compared, and the relationships of slopes with standard memory measures were determined RESULTS: Worse learning slopes were associated with more severe disease states, even after controlling for demographics, total learning, and cognitive severity.

Feasibility and acceptability of remote smartphone cognitive testing in frontotemporal dementia research.

Introduction: Remote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp).

Methods: A diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [ = 101]; prodromal: 0.

Distinguishing Semantic Variant Primary Progressive Aphasia from Alzheimer's Disease.

The differentiation of semantic variant primary progressive aphasia from dementia and Alzheimer's disease can be difficult, particularly when the semantic anomia is pronounced. This report describes a patient who presented with complaints of memory loss and proved to have prominent semantic loss of all types of nouns, common and proper, concrete and abstract, yet continued to live independently and maintain his activities of daily living. The evaluation was consistent for semantic variant primary progressive aphasia with degradation of semantic knowledge and focal anterior temporal atrophy and hypometabolism.

Plasma inflammation for predicting phenotypic conversion and clinical progression of autosomal dominant frontotemporal lobar degeneration.

Background: Measuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD).

Methods: We measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers () and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes).

A Transdisciplinary Program for Care of Veterans With Neurocognitive Disorders.

Background: Veterans face specific risk factors for neurocognitive disorders. Providing them with comprehensive care for dementia and related neurocognitive disorders is a challenge as the population ages. There is a need for family-centered interventions, specialized expertise, and collaboration among clinicians and caregivers.