Publications by authors named "Joseph Masdeu"
Introduction: Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD.
Methods: We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study.
Introduction: Early-onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%-8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early-onset dementia.
Methods: Data from 307 cognitively normal (CN) volunteer participants and those with amyloid-positive EOAD or amyloid-negative cognitive impairment (EOnonAD) were compared.
Introduction: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller-scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD.
Methods: Z-score cognitive-domain composites for 311 amyloid-positive sporadic EOAD and 314 amyloid-positive LOAD participants were calculated from baseline data from age-appropriate control cohorts.
Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.
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- Behavioral variant frontotemporal dementia (bvFTD) is characterized by a range of neuropsychiatric symptoms (NPS) that occur frequently both early and late in the illness, impacting emotional and behavioral aspects.
- A study involving 354 participants identified four main clusters of NPS—affective, disinhibited, compulsive, and psychosis—showing that some symptoms fluctuate while others remain stable over time.
- The findings suggest that NPS could be linked to specific brain network disruptions, providing insight for potential treatments, although the variability in symptoms indicates they may not be reliable indicators of disease progression.
Article Synopsis
- The study investigates the role of the genetic variant rs1990622 as a potential modifier of disease risk in frontotemporal lobar degeneration (FTLD), particularly among those with pathogenic variants.
- Researchers enrolled participants from the ALLFTD study, analyzing the impact of rs1990622 on gray matter volume and cognitive function across various genetic groups related to FTD.
- Results indicate that carriers of the minor allele of rs1990622 show increased gray matter volume and better cognitive performance, especially in the thalamus and among presymptomatic individuals.
Article Synopsis
- - Cardiovascular health, evaluated through Life's Simple 7 (LS7), is linked to slower cognitive decline and better brain integrity in patients with autosomal dominant frontotemporal lobar degeneration (FTLD).
- - A study involving 247 FTLD genetic variant carriers and 189 non-carrier controls found that those with better cardiovascular health had slower memory and language declines, as well as less accumulation of frontal white matter hyperintensities (WMHs).
- - Maintaining good cardiovascular health could be a key modifiable strategy to improve cognitive outcomes and brain health in individuals at risk for genetic forms of dementia.
Brain inflammation, with an increased density of microglia and macrophages, is an important component of Alzheimer's disease and a potential therapeutic target. However, it is incompletely characterized, particularly in patients whose disease begins before the age of 65 years and, thus, have few co-pathologies. Inflammation has been usefully imaged with translocator protein (TSPO) PET, but most inflammation PET tracers cannot image subjects with a low-binder TSPO rs6971 genotype.
View Article and Find Full Text PDFBackground: 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.
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- The study investigates the effect of a specific genetic modifier on gray matter volume and cognitive function in patients with Frontotemporal Lobar Degeneration (FTLD), including both mutation carriers and sporadic cases.
- Participants were recruited from the ALLFTD study and were genotyped for the rs1990622 SNP to assess the relationship between this genetic variant and cognitive outcomes across different genetic groups.
- Findings indicate that the minor allele of rs1990622 is associated with increased gray matter volume and better cognitive scores in mutation carriers, especially affecting the thalamus, suggesting it may play a role in modifying the risk and impact of FTLD.
Based on the anatomic proximity, connectivity, and functional similarities between the anterior insula and amygdala, we tested the hypothesis that the anterior insula is an important focus in the progression of TDP-43 pathology in LATE-NC. Blinded to clinical and neuropathologic data, phospho-TDP (pTDP) inclusion pathology was assessed in paired anterior and posterior insula samples in 105 autopsied patients with Alzheimer disease, Lewy body disease, LATE-NC and hippocampal sclerosis (HS), amyotrophic lateral sclerosis (ALS), and other conditions. Insular pTDP pathology was present in 34.
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- Frontotemporal lobar degeneration (FTLD) is a rare condition characterized by behavioral and motor symptoms, making traditional neuropsychological assessments less effective for early detection; smartphone-based cognitive tests may provide a solution for remote evaluations.
- A study conducted over four years involved 360 participants with varying stages of FTLD using smartphone apps to assess cognitive function, splitting them into discovery and validation groups, with a majority being asymptomatic or at preclinical stages.
- Results indicate the smartphone-based tests showed moderate to excellent reliability in measuring cognitive function, suggesting they could serve as valid tools for remote assessments in FTLD patients.
Background: Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies.
Objective: We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk.
Methods: We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results.
Trial Registration: ClinicalTrials.gov Identifier: NCT05821153, Registered April 20 2023, Retrospectively registered, https://classic.
Clinicaltrials: gov/ct2/show/NCT05821153.
Article Synopsis
- Researchers developed an MRI-based signature to identify brain atrophy linked to sporadic early-onset Alzheimer's disease (EOAD) using two patient samples, one small (n=25) and another larger (n=211).
- The study found consistent atrophy patterns in specific brain regions, like the caudal lateral temporal cortex and inferior parietal lobule, while the medial temporal lobe was relatively spared.
- The EOAD-signature atrophy correlates with cognitive impairment severity, suggesting it's a reliable biomarker for Alzheimer’s-related neurodegeneration in clinical trials.
Article Synopsis
- The LEADS study focuses on understanding the genetic causes of early-onset Alzheimer's Disease (EOAD), specifically in individuals aged 40-64, by screening for known pathogenic variants.
- *Whole exome sequencing of 299 participants found pathogenic variants in 1.35% of EOAD cases and 6.58% of early-onset non-Alzheimer's disease cases, but no gene showed a significant enrichment for rare functional variants.
- *The findings suggest that LEADS may include new genetic variants related to early-onset cognitive impairment, making it an important resource for ongoing Alzheimer's research.*
Foraging behavior requires weighing costs of time to decide when to leave one reward patch to search for another. Computational and animal studies suggest that striatal dopamine is key to this process; however, the specific role of dopamine in foraging behavior in humans is not well characterized. We use positron emission tomography (PET) imaging to directly measure dopamine synthesis capacity and D and D receptor availability in 57 healthy adults who complete a computerized foraging task.
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- The study focuses on analyzing baseline amyloid-beta and tau-PET scans in participants with early-onset Alzheimer's disease (EOAD) to improve diagnostic understanding.* -
- Out of the 321 cognitively impaired participants, 75.7% were classified as having EOAD based on amyloid-PET, with 95.1% of them also showing elevated tau-PET signals, particularly in younger and female subjects.* -
- The findings highlight the significance of using these biomarkers for more accurate EOAD diagnoses and suggest potential implications for treatment strategies based on tau-PET levels.*
Article Synopsis
- The study examines the Rey Auditory Verbal Learning Test (RAVLT) as a tool for assessing memory impairment in early-onset Alzheimer's disease (EOAD), focusing on the effects of amyloid presence and diagnostic syndrome.
- RAVLT recordings from 303 participants were analyzed, revealing that amyloid-positive individuals showed significant differences in memory performance compared to amyloid-negative individuals, including effects on raw scores and timing measures.
- The findings suggest that RAVLT is sensitive to variations in memory impairment linked to amyloid and syndrome types in EOAD, highlighting the need for further research to understand the predictive capabilities of these memory scores.
Neuroimaging is a valuable adjunct to the history and examination in the evaluation of motor system disorders. Conventional imaging with computed tomography or magnetic resonance imaging depicts important anatomic information and helps to identify imaging patterns which may support diagnosis of a specific motor disorder. Advanced imaging techniques can provide further detail regarding volume, functional, or metabolic changes occurring in nervous system pathology.
View Article and Find Full Text PDFIntroduction: 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.
Article Synopsis
- The Longitudinal Early Onset Alzheimer's Disease Study (LEADS) aims to identify fluid biomarker characteristics specific to early-onset Alzheimer's disease (EOAD).
- The study measured various cerebrospinal fluid (CSF) biomarkers in 165 participants, finding significant differences in certain biomarker levels between EOAD, cognitively normal individuals, and those with early-onset non-AD dementia.
- The results highlight the correlation between biomarkers and cognitive performance, particularly within the EOAD group, providing valuable insights for future clinical trials targeting sporadic EOAD.
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.
On September 25 and 26, 2021, the Alzheimer's Association hosted the first meeting focused on people with early-onset Alzheimer's disease (EOAD)-sometimes referred to as younger onset Alzheimer's disease (AD). Though a diagnosis of AD can be devastating at any age, those with a younger onset-defined as symptoms developing prior to 65 years of age-face unique challenges. EOAD occurs when people are in the prime of their lives, often with multiple responsibilities including careers, community activities, and raising children and caring for older family members.
View Article and Find Full Text PDFIntroduction: 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.