Do Depression and Agitation Signal Increased Risk of Alzheimer Disease in Patients with Mild Cognitive Impairment?

In patients with mild cognitive impairment (MCI), neuropsychiatric symptoms (NPS) may be associated with regional brain atrophy and a faster rate of cognitive decline, increasing the risk for progression to Alzheimer disease (AD).

Neuropsychiatric symptoms [such as agitation and depression are common in AD, but the association between NPS and brain atrophy in MCI—a precursor to AD—remains poorly understood. Identifying these connections can help detect early markers of AD and understand which patients are at higher risk for faster cognitive decline.

In this study, the researchers measured gray matter volume, cognitive status, and NPS in 81 patients with MCI. Participants were divided into groups based on the presence or absence of NPS and the specific symptoms exhibited. Gray matter volume was quantified, while cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI).

Key findings include a lower volume of the left temporal pole in patients with depression (P = .012) compared with those without NPS, and a reduced volume in the right middle occipital gyrus in patients with agitation (P = 0.003) compared with those without NPS. There was also a significant correlation between the volume of the left temporal pole and MMSE scores (r(78) = 0.232, P = .019). Patients with NPS exhibited lower cognitive performance than those without NPS (t(79) = 1.79, P = .038), as well as a faster cognitive decline (t(48) = -1.74, P = .044).

The main limitations of this study include its small sample size and the cross-sectional nature of the analysis, which may not capture the full scope of cognitive decline over time.

“... our longitudinal evidence highlights the relevance of an adequate identification of NPS in MCI patients to identify those at risk of faster cognitive decline,” the study authors concluded.

 Reference

Marin-Marin L, Renau-Lagranja J,  Ávila C, et al. Depression and agitation factors are related to regional brain atrophy and faster longitudinal cognitive decline in cognitive impairment. J Alzheimers Dis. 2024;97(3):1341-1351. doi: 10.3233/JAD-230929.