Cholinergic effect on Linking between Cerebral Perfusion and Cognition in Alzheimer Disease

Dementia has a growing incidence in western countries, mainly due to increasing life expectancy. The recently introduced acetylcholinesterase inhibitors, such as Donepezil, have been shown to slow down the course of the Alzheimer disease (AD), when administered at early stages. Nineteen patients (4 males, mean age 75.3 years +- 6.4,) affected with probable AD (NINCDS-ADRDA criteria) were examined twice, before and after a period (mean 10.6 +-2.9 months) of Donepezil oral administration (5 mg/day), by routine clinical and neuropsychological examination. At each time point, brain perfusional SPECT scan was performed. According to the variation of Mini-Mental State Examinations (MMSE) score, the group was divided into two subgroups: “responders” (MMSE variation ranging between +2 and -1, mean 0.18: 11 subjects) and “non responders” (MMSE variation between -2 and -7, mean -4.38). There was no difference between the two subgroups either for age or sex distribution. In each subgroup, the correlation between the MMSE score and perfusional value variations were assessed in Frontal and Parietal-temporal areas in each hemisphere. In responders there was a correlation between cerebral perfusion and cognitive changes, more significant in right ( frontal, p<0.01, and parietal-temporal areas, p<0.02 ) than in left ( p<0.05 in both areas) hemisphere, whereas in non responders no correlation was found. These preliminary data confirm that the cognitive effect of the anticholinesterase therapy, obtained only in a part (approximately a half) of AD patient, is supported by neural activity, that is tightly coupled to the perfusional levels.