Resting SPECT-neuropsychology correlation in very mild Alzheimer's disease

OBJECTIVE To investigate the relationships between brain function and some of the most frequently impaired cognitive domains in the first stages of Alzheimer's disease (AD), we searched for correlation between the scores on 3 neuropsychological tests and brain perfusion, assessed by single photon emission computed tomography (SPECT) in patients with very mild AD. METHODS Twenty-nine consecutive outpatients (mean age 78.2+/-5.5) affected by probable AD in the very mild phase (i.e. with a score > or =20 on the mini-mental state examination, MMSE) underwent brain SPECT with (99m)Tc-ethylcisteinate dimer. For correlative purposes, word list learning (by the selective reminding test, SRT), constructional praxis test (CPT) and visual search test (VST) were chosen a priori out of an extended battery employed to diagnose AD at first patient evaluation. Voxel-based correlation analysis was achieved by statistical parametric mapping (SPM99) with a height threshold of P=0.005. Age, years of education and the MMSE score were inserted in the correlative analysis as confounding variables. RESULTS The SRT score showed correlation with brain perfusion in 3 clusters of the left hemisphere, including the post-central gyrus, the parietal precuneus, the inferior parietal lobule and the middle temporal gyrus, and in one cluster in the right hemisphere including the middle temporal gyrus and the middle occipital gyrus. The CPT score was significantly correlated with brain perfusion in the parietal precuneus and the posterior cingulate gyrus in the left hemisphere, whereas the VST score gave a significant correlation with brain perfusion in a left cluster including the parietal precuneus and the superior temporal gyrus. CONCLUSIONS Cognitive impairment in very mild AD is reflected by brain dysfunction in posterior associative areas, with peculiar topographical differences proper of each domain. The parietal precuneus was a common site of correlation of all 3 neuropsychological tests. This region, together with the posterior cingulate and the superficial posterior temporal-parietal cortex, is thought to be affected by disconnection from the mesial temporal lobe, besides being directly affected by increased oxidative stress and by atrophy as well. The impairment of these areas is thought to contribute to cognitive decline in verbal memory, constructional praxis and visual sustained attention which are indeed among the earliest signs of cognitive impairment in AD. SIGNIFICANCE Assessing the relationships between neuropsychology and brain functional imaging is a key approach to clarify the pathophysiology of cognitive failure in AD; the specificity of these findings in AD remains to be proven through comparison with correlation achieved in matched controls.