Successful Scene Encoding in Presymptomatic Early-Onset Alzheimer's Disease

Area of Science:

• Neuroimaging
• Genetics
• Neurology

Background:

• Episodic memory brain regions are affected in preclinical Alzheimer's disease (AD).
• Identifying at-risk cognitively-normal individuals for AD remains challenging.

Purpose of the Study:

• To investigate if functional MRI can detect early functional changes in presymptomatic PSEN1 E280A mutation carriers during scene encoding.
• Assess brain activity differences in individuals with a genetic risk for early-onset AD.

Main Methods:

• Functional MRI (fMRI) was used to study scene encoding in 39 cognitively-normal individuals.
• Participants were from a Colombian kindred with the PSEN1 E280A mutation, a cause of autosomal dominant early-onset AD.
• A subsequent memory test was administered post-scan.

Main Results:

• PSEN1 mutation carriers showed hyperactivation in medial temporal lobe regions (hippocampus, parahippocampal formation) during successful scene encoding.
• This hyperactivation was observed when compared to age-matched non-carriers.

Conclusions:

• Medial temporal lobe hyperactivation during scene encoding is present in individuals genetically predisposed to AD, years before clinical onset.
• Findings suggest functional neuroimaging may aid in the early detection of preclinical AD.