Increased Functional Connectivity of the Precuneus in Individuals with a Family History of Alzheimer’s Disease

Abstract

Background: First-degree relatives of individuals with late-onset Alzheimer’s disease (AD) have increased risk for AD, with children of affected parents at an especially high risk. Objective: We aimed to investigate default mode network connectivity, medial temporal cortex volume, and cognition in cognitively healthy (CH) individuals with (FH+) and without (FH-) a family history of AD, alongside amnestic mild cognitive impairment (aMCI) and AD individuals, to determine the context and directionality of dysfunction in at-risk individuals. Our primary hypothesis was that there would be a linear decline (CH FH- > CH FH+ > aMCI > AD) within the risk groups on all measures of AD risk. Methods: We used MRI and fMRI to study cognitively healthy individuals (n = 28) with and without AD family history (FH+ and FH-, respectively), those with aMCI (n = 31) and early-stage AD (n = 25). We tested connectivity within the default mode network, as well as measures of volume and thickness within the medial temporal cortex and selected seed regions. Results: As expected, we identified decreased medial temporal cortex volumes in the aMCI and AD groups compared to cognitively healthy groups. We also observed patterns of connectivity across risk groups that suggest a nonlinear relationship of change, such that the FH+ group showed increased connectivity compared to the FH- and AD groups (CH FH+ > CH FH- > aMCI > AD). This pattern emerged primarily in connectivity between the precuneus and frontal regions. Conclusion: These results add to a growing literature that suggests compensatory brain function in otherwise cognitively healthy individuals with a family history of AD.

Antisaccadic eye movements in middle-aged individuals with a family history of Alzheimer's disease

“…Hitherto, compelling evidence has suggested that the disease course of AD is more likely to be an inverted U-shaped pattern than a continuous decline, meaning that people may experience a better functional stage before the decline of cognitive ability (Corriveau-Lecavalier et al, 2020 ). Findings from functional MRI-based studies revealed that individuals with an early stage of dementia or who were cognitively normal but at a higher risk of developing dementia (carrying the APOE4 allele or having a family history of dementia) presented with greater brain activation, supporting this inverse quadratic hyperactivation hypothesis (Bookheimer et al, 2000 ; Burggren et al, 2002 ; Bondi et al, 2005 ; Wierenga et al, 2013 ; Green et al, 2023 ). These altered hyperactivations in MRI may present corresponding functional changes and better performance during antisaccade trials.…”

Preclinical Brain Network Abnormalities in Patients with Subjective Cognitive Decline

“…Our imaging findings went in either direction, an increase or a decrease of functional connectivity within networks. A classical neurobiological interpretation of decreases and increases of connectivity are network disruption in the former case and compensatory mechanisms of brain plasticity in the latter case [62][63][64]. Main contribution to this interpretation comes from longitudinal studies, which documented an increase of functional connectivity passing from mild cognitive impairment status to dementia [65][66][67].…”