Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration.

Area of Science:

• Neurology
• Neuroimaging
• Cognitive Science

Background:

• Subtle cognitive difficulties can precede overt Alzheimer's disease (AD) symptoms.
• Understanding the early pathological changes associated with these difficulties is crucial for timely intervention.

Purpose of the Study:

• To determine the temporal sequence of objectively defined subtle cognitive difficulties (Obj-SCD) in relation to amyloidosis and neurodegeneration.
• To examine the trajectories of amyloid PET and medial temporal neurodegeneration in participants with Obj-SCD compared to cognitively normal (CN) and mild cognitive impairment (MCI) groups.

Main Methods:

• Utilized data from 747 Alzheimer's Disease Neuroimaging Initiative participants (305 CN, 153 Obj-SCD, 289 MCI).
• Employed neuropsychological testing, serial amyloid PET (¹⁸F-florbetapir), and structural MRI (entorhinal cortex thickness, hippocampal volume).
• Analyzed 4-year rates of change using linear mixed effects models.

Main Results:

• Amyloid accumulation was faster in the Obj-SCD group than the CN group.
• Both Obj-SCD and MCI groups showed faster entorhinal cortical thinning compared to CN.
• MCI group exhibited faster hippocampal atrophy than CN participants.

Conclusions:

• Obj-SCD is associated with faster amyloid accumulation and selective entorhinal cortical thinning, preceding MCI.
• Obj-SCD may be identified during the preclinical stage of amyloid deposition.
• Obj-SCD may serve as a sensitive, noninvasive predictor of early amyloidosis and neurodegeneration.