ACCUMULATION OF DEMENTIA RISK FACTORS ALTERS BRAIN REGIONS OF EPISODIC MEMORY: AN FMRI ANALYSIS

Abstract

Longitudinal research suggests that genetic, lifestyle, and environmental factors enhance one's risk for developing Alzheimer's disease and related dementias (ADRD). However, it is not known how an accumulation of multiple risk factors alters brain function. One barrier to this research is that increased risk for ADRD affects the cerebrovascular system, thus decoupling neural activity from the fMRI blood oxygen level dependent (BOLD) signal. Previous studies that have found an association between risks for ADRD and brain activity suffer challenges in interpretation because the BOLD signal was not calibrated, likely leading to an overestimation of such associations. We hypothesized that as the number of ADRD risk factors increase, brain regions within the medial temporal lobes and the default mode network (DMN) would exhibit altered brain activity during an episodic memory retrieval task. To reduce the influence of non-neural influences on the BOLD signal, several steps were taken to calibrate fMRI BOLD activity. Participants ranged in age from 50 to 70 years. Participants were recruited with varying levels of risk for dementia and from this initial screening a dementia risk score was calculated. They also underwent a neuropsychological battery to screen out possible dementia. Using fMRI, brain activity was assessed while participants completed a memory task by viewing a pair of pictures, followed by an alternative-forced-choice test, where participants viewed a picture cue and had to determine which of four pictures was paired with the cue. After correcting the fMRI BOLD signal, whole-brain analyses revealed that increased dementia risk was negatively associated with brain activity in the hippocampus—a task positive region—and was positively associated with the lateral parietal cortex—a task negative region. We found evidence that adults with an accumulation of risk factors for dementia exhibit decreased modulation of brain activity in critical regions underlying episodic memory. These findings call into question previous studies that did not calibrate the BOLD signal and found compensatory hyperactivity in these regions. Instead, cumulative risk likely represents early dysfunction of the default mode and brain regions underlying episodic memory.