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

Abstract

Having a parent with Alzheimer’s disease (AD) and related dementias confers a risk for developing these types of neurocognitive disorders in old age, but the mechanisms underlying this risk are understudied. Although the hippocampus is often one of the earliest brain regions to undergo change in the AD process, we do not know how early in the lifespan such changes might occur or whether they differ early in the lifespan as a function of family history of AD. Using a rare sample, young adults with a parent with late-onset dementia, we investigated whether brain abnormalities could already be detected compared with a matched sample. Moreover, we employed simple yet novel techniques to characterize resting brain activity (mean and standard deviation) and brain volume in the hippocampus. Young adults with a parent with dementia showed greater resting mean activity and smaller volumes in the left hippocampus compared to young adults without a parent with dementia. Having a parent with AD or a related dementia was associated with early aberrations in brain function and structure. This early hippocampal dysfunction may be due to aberrant neural firing, which may increase the risk for a diagnosis of dementia in old age.

Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knock in mouse model of Alzheimer’s disease

“…Despite the evident comorbidity between neuronal hyperactivity and AD during the prodromic stage in patients, the origin of neuronal hyperexcitability and hippocampal vulnerability remain debated 20,21 . It is noteworthy that some reports have described hippocampal hyperactivity in asymptomatic offspring of autopsy-confirmed AD patients 22,23 . Granted that such evidence is limited, it raises the hypothesis that hippocampal hyperexcitability may precede the prodromal stage also in humans.…”

Novel Approaches to Memory and Aging: The Editorial

“…They found brain-to-intracranial-volume ratio to be the most significant aspect in predicting age, followed by hippocampal volume, and discovered cortical thickness in temporal and parietal lobes to be more predictive than frontal and occipital lobes. In addition, McDonough et al [ 16 ] used structural and functional resting-state MRI to discover that younger adults with a parent with dementia show greater resting mean activity and smaller volume in the left hippocampus compared with those without, suggesting that having a parent with AD or a related dementia is associated with early aberrations in brain function and structure, possibly increasing the risk for a diagnosis of dementia in old age.…”