Frontal lobe hypoperfusion and depressive symptoms in Alzheimer disease

Depressive symptoms of varying severity are prevalent in up to 63% of Alzheimer disease (AD) patients and often result in greater cognitive decline and increased caregiver burden. The current study aimed to determine the neural correlates of depressive symptoms in a sample of AD patients.

Using the Cornell Scale for Depression in Dementia, we assessed 56 patients who met criteria for probable AD. Data obtained from Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (SPECT) were analyzed with the use of a magnetic resonance imaging-derived region of interest (ROI) anatomic template before and after atrophy correction and statistical parametric mapping (SPM). The following 4 frontal ROIs were investigated bilaterally: middle frontal gyrus (Brodmann's area [BA] 46), orbitofrontal cortex (BA 11), superior prefrontal (BA 8/9) and anterior cingulate (BA 24/25/32/33).

Depressive symptoms were present in 27 of the AD patients (48%). Patients with depressive symptoms showed less perfusion in the right superior and bilateral middle frontal gyri (p < 0.005), left superior frontal (p < 0.05) and anterior cingulate gyri (p < 0.005) before atrophy correction. SPM analyses revealed significantly lower perfusion in bilateral dorsolateral and superior prefrontal cortex of patients with depressive symptoms (right, p < 0.005; left, p < 0.05). SPECT ROI analyses with atrophy correction revealed trends similar to data without atrophy correction but did not reach statistical significance.

In this study, depressive symptoms in AD patients were associated with relative hypoperfusion in the prefrontal cortex when they were compared with AD patients without depressive symptoms. These findings are consistent with previous reports in studies of primary depression suggesting that these regions are involved in affect and emotional regulation.