Differences in brain metabolism associated with agitation and depression in Alzheimer's disease

Agitation and depression are among the commonest behavioural and psychological symptoms exhibited by Alzheimer's disease patients. However, their pathophysiology remains unclear. We therefore investigated the relationship between the brain metabolism in the posterior cingulate gyrus and the dorsolateral prefrontal cortex, and agitation and depression in patients diagnosed with Alzheimer's disease.

We recruited 26 patients (14 women and 12 men) with a mean age of 75 years and probable Alzheimer's disease. All patients completed the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale-Short Form (GDS) assessment, and the Cohen-Mansfield Agitation Inventory (CMAI) in order to evaluate cognition, depression, and agitation, respectively. All subjects underwent magnetic resonance imaging and (1)H-magnetic resonance spectroscopy of the brain. The ratios of N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI) to creatine (Cr) in the posterior cingulate gyrus and the dorsolateral prefrontal cortex were measured and compared with neuropsychological test results.

The MMSE scores correlated positively with the NAA/Cr ratio in the left posterior cingulate gyrus (r = 0.56; p = 0.001). The CMAI scores correlated negatively with the NAA/Cr ratio in the left posterior cingulate gyrus (r = -0.46; p = 0.02). The GDS scores correlated positively with the Cho/Cr ratio in the left dorsolateral prefrontal cortex (r = 0.59; p = 0.01), and mI/Cr in both left (r = 0.47; p = 0.03) and right (r = 0.47; p = 0.03) cingulate gyri.

Agitation and depression levels correlated with different neurochemical metabolites in specific brain areas. We conclude that various neuropsychiatric symptoms might have separate pathophysiologies.