Publications by authors named "Sandra Weintraub"

Disinhibition is one of the most distressing and difficult to treat neuropsychiatric symptoms of dementia. It involves socially inappropriate behaviours, such as hypersexual comments, inappropriate approaching of strangers and excessive jocularity. Disinhibition occurs in multiple dementia syndromes, including behavioural variant frontotemporal dementia, and dementia of the Alzheimer's type.

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Article Synopsis
  • Pick's disease (PiD) is a type of tauopathy linked to frontotemporal lobar degeneration, manifesting in dementia syndromes like primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD).
  • The study examined brain distributions of Pick bodies in cases of bvFTD and PPA using brain tissue samples, specifically targeting areas such as the middle frontal gyrus and anterior temporal lobe for pathology.
  • Findings showed that bvFTD had higher densities of Pick bodies in the frontal region, while PPA showed more in the temporal lobe, with both disorders exhibiting significant hippocampal pathology that did not align with neocortical findings.
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Objective: Symptom clustering research provides a unique opportunity for understanding complex medical conditions. The objective of this study was to apply a variable-centered analytic approach to understand how symptoms may cluster together, within and across domains of functioning in mild cognitive impairment (MCI) and dementia, to better understand these conditions and potential etiological, prevention, and intervention considerations.

Method: Cognitive, motor, sensory, emotional, and social measures from the NIH Toolbox were analyzed using exploratory factor analysis (EFA) from a dataset of 165 individuals with a research diagnosis of either amnestic MCI or dementia of the Alzheimer's type.

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Objective: The percentage of older adults living into their 80s and beyond is expanding rapidly. Characterization of typical cognitive performance in this population is complicated by a dearth of normative data for the oldest old. Additionally, little attention has been paid to other aspects of health, such as motor, sensory, and emotional functioning, that may interact with cognitive changes to predict quality of life and well-being.

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Studies on the neural bases of sentence production have yielded mixed results, partly due to differences in tasks and participant types. In this study, 101 individuals with primary progressive aphasia (PPA) were evaluated using a test that required spoken production following an auditory prime (Northwestern Assessment of Verbs and Sentences-Sentence Production Priming Test, NAVS-SPPT), and one that required building a sentence by ordering word cards (Northwestern Anagram Test, NAT). Voxel-Based Morphometry revealed that gray matter (GM) volume in left inferior/middle frontal gyri (L IFG/MFG) was associated with sentence production accuracy on both tasks, more so for complex sentences, whereas, GM volume in left posterior temporal regions was exclusively associated with NAVS-SPPT performance and predicted by performance on a Digit Span Forward (DSF) task.

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Importance: Nomenclature in the field of neurodegenerative diseases presents a challenging problem. Inconsistent use of terms such as Alzheimer disease and dementia has compromised progress in clinical care, research, and development of therapeutics. Dementia-associated stigma further contributes to inconsistent and imprecise language.

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Emotional functioning in older adults is influenced by normal aging and cognitive impairment, likely heterogeneous across positive versus negative aspects of emotional functioning. Little is known about positive emotional experiences at the early stages of cognitive impairment. We assessed different aspects of emotional functioning among 448 participants aged 65+ (Normal Control (NC) = 276, Mild Cognitive Impairment (MCI) = 103, and mild dementia of the Alzheimer type (mild DAT) = 69) and tested moderators.

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Background: Mild cognitive impairment is common in Parkinson disease (PD-MCI). However, instability in this clinical diagnosis and variability in rates of progression to dementia raises questions regarding its utility for longitudinal tracking and prediction of cognitive change in PD. We examined baseline neuropsychological test and cognitive diagnosis predictors of cognitive change in PD.

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Introduction: Olfactory decline is associated with cognitive decline in aging, amnestic mild cognitive impairment (aMCI), and amnestic dementia associated with Alzheimer's disease neuropathology (ADd). The National Institutes of Health Toolbox Odor Identification Test (NIHTB-OIT) may distinguish between these clinical categories.

Methods: We compared NIHTB-OIT scores across normal cognition (NC), aMCI, and ADd participants (N = 389, ≥65 years) and between participants positive versus negative for AD biomarkers and the APOE ε4 allele.

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Article Synopsis
  • - The study addresses the issue of limited ancestral diversity in genome-wide association studies (GWAS), which makes it hard to find genetic risk variants in non-European ancestry groups, focusing on Alzheimer's Disease (AD).
  • - Researchers analyzed a multi-ancestry GWAS dataset within the Alzheimer's Disease Genetics Consortium (ADGC) involving individuals from various ancestries, identifying 13 shared risk loci and 3 ancestry-specific loci, highlighting the benefits of diverse samples.
  • - The findings underscore the importance of including underrepresented populations in genetic research, suggesting that even smaller sample sizes can lead to the discovery of novel genetic variants related to AD and implicating specific biological pathways like amyloid regulation and neuronal development.
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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.

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Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy.

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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.

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The anatomical distribution of most neurodegenerative diseases shows considerable interindividual variations. In contrast, frontotemporal lobar degeneration with transactive response DNA-binding protein type C (TDP-C) shows a consistent predilection for the anterior temporal lobe (ATL). The relatively selective atrophy of ATL in TDP-C patients has highlighted the importance of this region for complex cognitive and behavioral functions.

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Article Synopsis
  • - The study highlights that European local ancestry (ELA) related to the APOE ε4 gene increases the risk of Alzheimer's disease (AD) more than African local ancestry (ALA), with ELA showing higher APOE ε4 expression in AD brains.
  • - Researchers conducted experiments on brain samples from six ALA and six ELA AD patients, finding that chromatin accessibility is greater at the APOE ε4 promoter in ELA astrocytes, which may explain the higher expression levels.
  • - The findings indicate that this increased chromatin accessibility in ELA astrocytes is linked to genes involved in synapsis, cholesterol processing, and astrocyte response, ultimately contributing to the heightened AD risk seen in ELA compared
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Background: The COVID-19 pandemic has had a widespread impact on sleep quality, yet little is known about the prevalence of sleep disturbance and its impact on self-management of chronic conditions during the ongoing pandemic.

Objective: To evaluate trajectories of sleep disturbance, and their associations with one's capacity to self-manage chronic conditions.

Design: A longitudinal cohort study linked to 3 active clinical trials and 2 cohort studies with 5 time points of sleep data collection (July 15, 2020 - May 23, 2022).

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  • Empathy, the ability to understand how others feel, is affected early on in a disease called bvFTD, which makes people behave differently.
  • The study followed 431 people with different types of FTD and found that their ability to empathize decreased as the disease got worse, especially between the first signs of symptoms and very mild symptoms.
  • By measuring empathy using a specific questionnaire, researchers can track how it changes over time, which could help in treating people with this disease.
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Introduction: The National Institutes of Health (NIH) Toolbox (NIHTB) provides computerized measures of cognition, emotion, sensation, and motor abilities across the lifespan. The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study validated the NIHTB in individuals across the cognitive aging spectrum. This article reports the characteristics of our sample of participants.

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