RESUMO
In contrast to depression, motor symptoms in PD have been extensively researched. The result is a detailed understanding of the pathophysiology of abnormal movements (162). Commitment to, and funding for, a well thought-out depression research plan, such as that presented by the working group at the National Institutes of Health (6), will bring similar theoretical understanding and patient relief for the most disabling of all PD symptoms (3-5)--depression.
Assuntos
Depressão/etiologia , Doença de Parkinson/complicações , Animais , Monoaminas Biogênicas/metabolismo , Química Encefálica , Demografia , Depressão/metabolismo , Diagnóstico por Imagem , Humanos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fatores de RiscoRESUMO
Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson's disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity.
Assuntos
Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/uso terapêutico , Indanos/uso terapêutico , Movimento/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Piperidinas/uso terapêutico , Análise de Variância , Fenômenos Biomecânicos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Donepezila , Método Duplo-Cego , Feminino , Humanos , Masculino , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Tomografia por Emissão de Pósitrons/métodosRESUMO
Early-stage nondemented Parkinson's disease (PD(es)) patients can learn short but not long sequences as well as controls. We have previously shown that to achieve normal performance, PD(es) patients activated the same right-sided cortical regions as controls plus the homologous left sided cortex and bilateral cerebellum. In this study, we evaluated two related hypotheses to explain the behavioral abnormalities and the increased bilateral brain activation observed in the PD(es) group. Hypothesis 1 proposed that PD(es) patients recruit regions from a normal bilateral network specialized for sequence learning that healthy controls would activate if performing difficult tasks. Thus, PD(es) patients can learn short sequences as well as controls. Hypothesis 2 proposed that information processing within the network in the PD(es) group is impaired. Thus, PD(es) patients cannot learn as difficult a sequence as controls. To test hypothesis 1, we increased task difficulty and statistical power in the control group and showed that the control and the PD(es) groups activated the same regions. To test hypothesis 2, we analyzed the equal performance data using two partial least squares (PLS) multivariate analyses. The task-PLS analysis showed that to perform equally with controls, the PD(es) group expressed the normal bilateral network more than the control group. The behavior-PLS analysis showed that the correlation between learning performance and regional activation was significantly different between the groups. We conclude that PD(es) patients have near normal learning if task difficulty is moderate because they can recruit additional regions from a normal bilateral network specialized for sequence learning. However, when a difficult task would normally require bilateral activation, PD(es) patients fail to learn because information processing within the network is impaired. Hum. Brain Mapp. 20:246-258, 2003.