BACKGROUND AND PURPOSE. Donepezil, an acetylcolinesterase inibitor, is one of the main current therapeutic approach to Alzheimer’s disease (AD). Modest but significant clinical and neuropsychological effects have been documented in a part of patients by longitudinal studies versus placebo. Despite these relevant effects on a previously intractable disease, the effect of chronic donepezil therapy on brain functional parameters is still scantly known. In the only study evaluating brain SPECT before and during donepezil therapy, a mild diffuse rCBF increase was found. METHODS. Nineteen patients (15 women, 4 men, mean age: 75.3 years +- 6.4) affected with mild probable AD (NINCDS-ADRDA criteria) underwent brain SPECT with Tc-99m-HMPAO and a brain-dedicated, high-resolution camera (CERASPECT, Digital Sci., Waltham, MA). The Mini-Mental Status Examination (MMSE) was chosen as a synoptic index of cognitive deterioration (range: 14-26, mean 19.6 +-3.5). All patients regularly received oral Donepezil (5 mg/day). After a mean time of 10.6 months +-2.9, they were re-evaluated by routine clinical and neuropsychological examinations, and by SPECT. SPM99 was used to co-registrate pre- and during donepezil therapy SPECTs. In each SPECT examination, mean counts per pixel of each ROI was normalized on mean counts per pixel of the whole cerebellum. Moreover, a new value for every pixel was calculated as follows: Z=(x-xm)/SD, where x=count value, xm= ROI average, SD= standard deviation obtaining a Standardised Normal Distribution (SND). To the purpose of the present study, SPECT values were then expressed as their SND values. According to MMSE score changes, patients were arbitrary divided into two subgroups, i.e.: responders (MMSE change ranging between +2 and -1, mean 0.18 +-1.3: 11 patients, mean age: 73.3 +-5.5; mean MMSE at basal SPECT: 19.6 +-3.9) and non-responders (MMSE change between -2 and -7, mean -4.38 +-1.6: 8 patients, mean age: 78 +-7; mean MMSE at basal SPECT: 19.6 +-3.8). The difference of Standard Deviation between SND SPECT values during donepezil therapy and values before therapy was computed. It was analysed finding a value SDT (standard deviation threshold) ranging from 0.34 and 0.43, which corresponds to the 11% of the full SD range. RESULTS. The reliability of concordance between y(SD)= SD95%, while the reliability of concordance between cerebellum normalization and MMSE is only 79%. The concordance between MMSE and y(SD) in identifying responders and non-responders was 63% (p=0.05 by chi-square test). CONCLUSION. The 63% concordance between y(SD) and MMSE in identifying patients who respond or do not to Donepezil therapy justifies the application of this statistical approach on a wider sample of patients to improve responder recognition and thus to avoid unnecessary drug administration.
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|Titolo:||Standardised Normal Distribution Analysis on SPECT Datasets before and donepezil in Alzheimer’s Disease|
|Data di pubblicazione:||2001|
|Appare nelle tipologie:||04.02 - Abstract in atti di convegno|