Objectives: Grey matter atrophy in the right hemisphere has been shown to be more severe in dementia patients
with delusions, suggesting a neuroanatomical localization that may be pertinent to impending neurodegeneration. Delusional
symptoms may arise when atrophy in these areas reduces the regulatory functions of the right hemisphere, in tandem
with asymmetric neuropathology in the left hemisphere. We hypothesized that delusional patients with either amnestic
mild cognitive impairment (MCI) or early Alzheimer Disease (AD) would experience more pronounced grey matter atrophy
in the right frontal lobe compared with matched patients without delusions. Methods: We used neuroimaging and
clinical data obtained from the Alzheimer’s Disease Neuroimaging Initiative. A comparison group of twenty-nine nondelusional
MCI/early AD participants were compared with twenty-nine delusional participants using voxel-based morphometry,
matched at baseline by age, sex, education, and Mini-Mental State Exam score. All included participants were
diagnosed with amnestic MCI at study baseline. Results: Fifteen voxel clusters of decreased grey matter in participants
with delusions were detected. Prominent grey matter decrease was observed in the right precentral gyrus, right inferior
frontal gyrus, right insula, and left middle occipital gyrus, areas that may be involved in control of thought and emotions.
Conclusion: Greater right fronto-temporal grey matter atrophy was observed in MCI or early AD participants with delusions
compared to matched patients without delusions. Consistent with our predictions, asymmetric grey matter atrophy in
the right hemisphere may contribute to development of delusions through loss of executive inhibition.