Basic Science and Pathogenesis

Area of Science:

• Neuropathology
• Neuropsychiatry
• Neurodegenerative Diseases

Background:

• Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders and can precede cognitive decline.
• Understanding the link between neuropathological lesions and NPS in younger and middle-aged adults is crucial for identifying early disease markers.

Purpose of the Study:

• To investigate the association between specific neuropathological substrates and common NPS in adults aged 30-64 years.
• To explore the prevalence of NPS in relation to cognitive status in this age group.

Main Methods:

• Population-based post-mortem study of 413 individuals (aged 30-64).
• Assessed neuropathology (NFT, amyloid-β, Lewy bodies, TDP-43, infarcts, CAA, atherosclerosis) and NPS (Neuropsychiatric Inventory).
• Used adjusted models to evaluate relationships between neuropathology and seven NPS, and compared NPS frequency based on cognitive status (CDR).

Main Results:

• NPS were more common in individuals with cognitive impairment.
• Depression and anxiety correlated with neurofibrillary tangle (NFT) stages.
• Anxiety linked to cerebral amyloid angiopathy (CAA); agitation, irritability, and delusions associated with lacunar infarcts.

Conclusions:

• Vascular lesions show a significant relationship with specific neuropsychiatric symptoms.
• Findings underscore the potential of vascular pathology as a contributor to NPS in middle-aged adults.