Background: Many patients present to our clinic with primarily executive rather than amnestic impairments. Recently, Townley and colleagues proposed criteria for a progressive dysexecutive syndrome (PDS). To date, PDS has been reported to be more common in younger individuals (55-65 years old) and is associated with Alzheimer's biomarkers (AD). Less is known about the genetic and neuroinflammatory profile of patients with PDS.
Method: We report the clinical, biomarker, genetic, and autopsy data of a participant from the Center for Translational and Neuroscience (CNTN) meeting criteria for PDS.
Result: A 57-year-old left-handed male presented with primary executive difficulties (bill paying, financial difficulties). Apathy was the only behavioral symptom reported. His initial neuropsychological testing showed impairments across a broad range of executive measures which worsened significantly over three years. Biomarker testing was consistent with Alzheimer's disease (A+T+N+) with a significant elevation in plasma p-tau 181 and neuroimaging showing peak involvement of the parietal lobes. Several plasma markers of neuroinflammation were elevated (GFAP, NFL) while others were depressed (IL-6, IL-10, TNF-alpha). He was negative for autosomal dominant mutations (PS1, PS2, APP) but carried two apolipoprotein E4 genes (APOE 4/4) with an elevated polygenic risk score. Exome sequencing revealed polymorphisms within several known risk genes: CR1, PICALM, ABCA7. After experiencing a rapid cognitive decline, the participant died only five years after the onset of symptoms. Due to sparse neurofibillary tanges in the mesial temporal cortex he was characterized as having "hippocampal sparring" Alzheimer's disease.
Conclusion: Progressive dysexecutive syndrome is a newly described variant of AD that affects younger individuals, causes impairments in executive functioning, and primarily impacts the fronto-parietal networks. Findings from our case report suggest a possible neuroinflammatory susceptibility and multi-factorial genetic basis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/alz.092098 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clinical Manifestations.
Alzheimers Dement
December 2024
Università di Modena e Reggio Emilia, Modena, Italy.
Background: Diagnosis in patients with Mild Behavioural Impairment (MBI) and with Mild Cognitive Impairment (MCI) with predominant executive deficits (eMCI) is often challenging, as they may be representing the early phase of both Alzheimer's Dementia (AD) as well as behavioural variant Frontotemporal Dementia (bvFTD). If neuropathology biomarkers aren't available, diagnosis is even more difficult. We evaluated the performance of classification of different clinical diagnostic criteria for behavioural/dysexecutive AD (without biomarkers) in MBI and eMCI.
View Article and Find Full Text PDFClinical Manifestations.
Alzheimers Dement
December 2024
University of Nevada Las Vegas, Las Vegas, NV, USA.
Background: Many patients present to our clinic with primarily executive rather than amnestic impairments. Recently, Townley and colleagues proposed criteria for a progressive dysexecutive syndrome (PDS). To date, PDS has been reported to be more common in younger individuals (55-65 years old) and is associated with Alzheimer's biomarkers (AD).
View Article and Find Full Text PDFAssociation of Early fMRI Connectivity Alterations With Different Cognitive Phenotypes in Patients With Newly Diagnosed Parkinson Disease.
Neurology
January 2025
From the IRCCS Neuromed (M.I.D.B., G.L., S.P., A.C., A.B., G.F., P.P., D.B.), Pozzilli; Department of Human Neurosciences (A.O., G.L., C.P., S.P., M.C., F.D.A., S.B., R.M., G.B., A.C., A.B., G.F., P.P., D.B.), Sapienza University of Rome; Department of Microscopic and Ultrastructural Anatomy (G.V.), Campus Biomedico University of Rome; Department of Neuroscience (M.C.), Istituto Superiore di Sanità, Rome; and Cognitive and Motor Rehabilitation and Neuroimaging Unit (F.D.A.), IRCCS Fondazione Santa Lucia, Rome, Italy.
Background And Objectives: According to the dual syndrome hypothesis, patients with Parkinson disease (PD) with visuospatial deficits are more likely to progress to dementia, compared with patients with a prevalent dysexecutive syndrome. In this study, we aimed to investigate whether early connectivity changes in the dorsolateral prefrontal cortex (DLPFC) and the precuneus (PCun)-which are critical to fronto-executive and visuospatial functions, respectively-can identify distinct cognitive phenotypes in cognitively intact newly diagnosed patients with PD.
Methods: Newly diagnosed, drug-naïve patients with PD (≤2 years from clinical onset) with normal Montreal Cognitive Assessment (MoCA), were consecutively enrolled from our Movement Disorders Clinics in Italy.
Article Synopsis
- The article reviews four atypical variants of Alzheimer’s disease: dysexecutive AD, behavioral variant AD, posterior cortical atrophy, and logopenic primary progressive aphasia, highlighting their unique clinical features and management needs.
- Recent research shows these variants differ in clinical symptoms and neuroanatomy, with specific brain regions being affected, but traditional amyloid imaging does not always correlate with these differences.
- Atypical AD forms often show non-memory symptoms, requiring modern diagnostic tools like MRI and PET for accurate differentiation, and emphasizing the need for personalized treatment plans that integrate both medication and non-drug therapies.
Patterns of brain volume and metabolism predict clinical features in the progressive supranuclear palsy spectrum.
Brain Commun
July 2024
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Article Synopsis
- Progressive supranuclear palsy (PSP) is a complex neurodegenerative disease characterized by diverse clinical symptoms, and this study explores patterns of brain atrophy and metabolic changes associated with different PSP subtypes.
- A total of 111 PSP patients were analyzed using both MRI and FDG-PET scans to identify how these imaging techniques correlate with specific clinical features like postural instability and ocular motor issues.
- Results indicate that imaging techniques are more effective at identifying the presence of symptoms rather than their severity, with FDG-PET being particularly good at detecting cortical abnormalities and MRI better at identifying subcortical issues, highlighting distinct neuroanatomical predictors for various symptoms.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!