Biomedical subjects

Guido Rodriguez

Publications and source records attributed to Guido Rodriguez.

21 records · Page 2Linked to original sources

PubMed2002

Effects of long-term Donepezil therapy on rCBF of Alzheimer's patients.

BACKGROUND: The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer's Disease (AD) has led to the need to assess the brain's response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period. METHODS: Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2+/-7.2; mean Mini-Mental State Examination score, MMSE: 19.8+/-3.5) underwent (t0) brain SPECT with 99mTc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t1) after 11+/-2.6 months of chronic Donepezil administration (5mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4+/-5.7, MMSE score: 20.6+/-3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13+/-1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings. RESULTS: The MMSE score declined significantly (P<0.01) from t0 to t1 both in untreated (from 20.6+/-3.5 to 17.8+/-4.4) and in treated (from 19.8+/-3.5 to 17.8+/-4.1) group. At t(0), the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t0 and t1, significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t1. By covariate SPM analysis between t0 and t1 in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region. CONCLUSIONS: Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients.

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PubMed2002

Quantitative EEG changes in Alzheimer patients during long-term donepezil therapy.

Twenty patients affected with probable mild-to-moderate Alzheimer's disease (AD; NINCDS-ADRDA criteria; 14 women and 6 men, mean age 75.2 +/- 7.1 years) who regularly received an oral acetylcholinesterase inhibitor (AChEI; donepezil 5 mg/day; Dz group) were compared with a control group of 11 AD patients (6 women and 5 men, mean age 73.5 +/- 6.0 years) diagnosed and followed up in the pre-AChEIs era (C group). At basal evaluation (t(0)), the 2 groups were comparable for age, education, and severity of disease (Global Deterioration Scale). All patients underwent quantitative EEG (qEEG, average reference, 10-20 International System), and were reexamined about 1 year later (t(1); i.e., after 12.3 +/- 3.6 months the Dz group, and after 13.7 +/- 3.9 months the C group). Log-transformed values of two qEEG bands, i.e. 2-6 and 6.5-12 Hz, were averaged between adjacent channels (frontal F3 and F7, F4 and F8; parietotemporal P3 and T7, P4 and T8) to obtain a qEEG ratio (6.5-12/2-6 Hz.) from one frontal and one temporoparietal region in each hemisphere. Neuropsychological impairment was summarized by the Mini-Mental Status Examination (MMSE). At t(0), both the MMSE score and the qEEG ratio values were somewhat higher in the C than in the Dz group, although nonsignificantly. Between t(0) and t(1), the MMSE score decreased significantly (p < 0.01) more in the C group (-4.36 +/- 2.25) than in the Dz group (-1.45 +/- 2.16), as did the qEEG ratio in the right frontal region (p < 0.01), whereas in the left frontal region the significance level was not reached (p = 0.02). Between t(0) and t(1), the qEEG ratio difference in both frontal regions and in the right temporoparietal region significantly correlated with the MMSE difference (p < 0.01), but neither with time between examinations nor with the difference on the Visual Search Test score. Long-term treatment with Dz led to a lesser deterioration of qEEG, paralleling a milder neuropsychological decline. The effect was significant in frontal regions, possibly because they are relatively spared during the mild-to-moderate phases of the disease.

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PubMed2002

Brain perfusion follow-up in Alzheimer's patients during treatment with acetylcholinesterase inhibitors.

UNLABELLED: Transient cognitive and behavioral stabilization of patients with Alzheimer's disease (AD) is the main goal of long-term acetylcholinesterase inhibitor (AChEI) therapy, but response to treatment is variable and, indeed, only some of the patients are stabilized. This is usually assessed by means of clinical and neuropsychologic scales, whereas functional neuroimaging could allow objective evaluation of the topographic correlates of the effect of therapy on brain functioning. The aim of this study was to evaluate brain perfusion changes by SPECT in AD patients during chronic AChEI therapy in relation to their cognitive evolution. METHODS: Forty-seven consecutive outpatients with mild-to-moderate probable AD (as defined by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association and the Diagnostic and Statistical Manual of Mental Disorders [4th edition criteria] and a score of > or =15 on the Mini-Mental State Examination [MMSE]) were enrolled in 2 centers over a 1-y period and underwent SPECT with 99mTc-hexamethylpropyleneamine oxime at the time of enrollment (t(0)). All of them started AChEI therapy. Nine patients were lost at follow-up, and drugs were withdrawn from 3 patients. Of the remaining 35 patients, who received regular AChEI therapy (donepezil, 5 or 10 mg/d; rivastigmine, 6 or 9 mg/d) throughout the observation period, only the 31 patients receiving donepezil were considered to avoid the possible confounding effect of different drugs. The 31 patients completed the study and a second SPECT examination was performed 15.0 +/- 3.0 mo later (t(1)). They were divided into stabilized (17 patients) and nonstabilized (14 patients) subgroups on the basis of the minimum expected annual rate of decline of the MMSE score, derived from a meta-analysis of the literature. SPECT data were analyzed by means of statistical parametric mapping. RESULTS: At baseline, the stabilized and nonstabilized patients were comparable for age, sex distribution, education, MMSE scores, memory impairment (selective reminding test [SRT]), apolipoprotein E genotype, AChEI dose regimen, and SPECT findings. The SRT scores decreased significantly (P < 0.01) in the nonstabilized subgroup but not in the stabilized subgroup. No significant difference was found between the baseline and repeated SPECT data in the stabilized subgroup. In contrast, in the nonstabilized subgroup a significant perfusion reduction was found in the frontal, temporal, and parietal superficial cortex and in the occipital precuneus in the right hemisphere and in the frontal and mesial temporal cortex in the left hemisphere. On repeated SPECT, regional cerebral blood flow was significantly lower in a left frontal region in the nonstabilized group than in the stabilized group. CONCLUSION: The regional cerebral blood flow decreases in several cortical regions in AD patients with cognitive deterioration despite long-term AChEI therapy, similar to that observed in untreated patients, whereas it remains stable in AD patients with stabilized cognitive performance during therapy.

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