Neurodevelopmental Vulnerability in Alzheimer's Disease and Frontotemporal Dementia

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Neurodevelopmental disorders (NDDs) may impact Alzheimer's disease (AD) and frontotemporal dementia (FTD) progression.
• Previous research focused on specific NDD-AD/FTD pairings, neglecting a dimensional approach to NDDs and AD/FTD heterogeneity.
• Investigating neurodevelopmental vulnerability (DV) in relation to AD/FTD clinical presentation and onset age is crucial.

Purpose of the Study:

• To explore the association between neurodevelopmental vulnerability (DV) and the clinical presentation of Alzheimer's disease (AD) and frontotemporal dementia (FTD).
• To determine if DV influences the age of onset in individuals with AD/FTD.
• To utilize a data-driven clustering approach for unbiased classification of DV.

Main Methods:

• Prospective recruitment of 84 AD/FTD participants and 41 matched controls.
• Classification of AD/FTD participants into typical (amnestic AD, behavioral FTD) and atypical (PPA, variants of AD, variants of FTD) presentations.
• Neuropsychological assessment and a novel NDDs symptoms questionnaire, followed by k-means clustering to identify DV+ and DV- groups.

Main Results:

• DV frequencies were similar between AD/FTD (18%) and control (15%) groups, and between typical (21%) and atypical (11%) AD/FTD subgroups.
• DV+ patients exhibited significantly earlier symptom onset by 8.0 years compared to DV- patients (p=0.005).
• The median age of onset for DV+ patients was 58 years.

Conclusions:

• Neurodevelopmental vulnerability (DV) may predispose individuals to early-onset Alzheimer's disease (AD) and frontotemporal dementia (FTD).
• DV does not appear to influence susceptibility to typical versus atypical variants of AD/FTD.
• Further research into the neurophysiological underpinnings of DV is needed for precision medicine and individualized treatment strategies in AD/FTD.