Dementia Risk Elevates Brain Activity During Memory Retrieval: A Functional MRI Analysis of Middle Aged and Older Adults

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 such factors impact brain functioning. One barrier to this research is that increased risk for ADRD affects the cerebrovascular system and, therefore, alters the link between neural activity and the fMRI BOLD signal. To better interpret fMRI findings, several steps were taken to adjust fMRI activity thereby reducing such cerebrovascular effects. We hypothesized that as the number of ADRD risk factors increase, brain regions within the medial temporal lobes and the default mode network would exhibit altered brain activity during an episodic memory retrieval task. Middle-aged and older adults (aged 50-74) free of dementia were recruited with varying levels of risk and underwent a neuropsychological battery and fMRI. In the memory task, participants viewed a pair of pictures. In an alternative-forced-choice test, participants viewed a picture cue and had to determine which of four pictures was paired with the cue. Increased dementia risk was positively associated with brain activity in regions of interest within the default mode network, the hippocampus, and the entorhinal cortex during memory retrieval. Whole-brain analyses revealed additional positive associations in prefrontal and occipito-temporal cortices. Risk factors most contributing to these elevated levels of brain activity included hypertension, diabetes, obesity, and cholesterol. We also ruled out confounds due to in-scanner performance and premorbid ability. Cumulative risk might represent early signs of burnout in brain regions underlying episodic memory.

Editorial: Insights in neurocognitive aging and behavior: 2021

“…Other approaches highlight the growing need to incorporate adults in middle-age rather than assuming the underlying mechanisms related to cognitive decline and brain alterations start in older age. Doing so pushes the boundary of early detection and moves toward life course approaches to our understanding of neurocognitive aging (McDonough et al, 2019 ).…”

Young Adults with a Parent with Dementia Show Early Abnormalities in Brain Activity and Brain Volume in the Hippocampus: A Matched Case-Control Study

“…In contrast, more recent studies have proposed that such hyperactivity may signal the beginning stages of hippocampal failure [29,67,71]. While many potential mechanisms at the neural level have been proposed to explain the deleterious view of hippocampal hyperactivity, one popular hypothesis points to the role of metabolic demands in specific brain regions such as the hippocampus.…”

Pet ownership is associated with greater cognitive and brain health in a cross-sectional sample across the adult lifespan

“…Data were used from the Alabama Brain Study on Risk for Dementia ( McDonough et al, 2019 ). One of the goals of the study was to uncover evidence for new potential protective factors for cognitive and brain health in middle-aged and older adults at varying risk for dementia along with a comparative sample of young adults.…”