RESUMO
OBJECTIVE: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. METHODS: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. RESULTS: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36-60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = -2.35 to -1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = -2.14 to -1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = -1.80 to -1.18). INTERPRETATION: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424-435.
Assuntos
Cognição/fisiologia , Estimulação Encefálica Profunda/métodos , Glucosilceramidase/genética , Heterozigoto , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos , Doença de Parkinson/genética , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologiaRESUMO
Glossolalia can be regarded as an instance of speech production in which practitioners produce syllables in seemingly random sequences. However, a closer inspection of glossalalia's statistical properties reveals that sequences show a Zipfian pattern similar to natural languages, with some syllables being more probable than others. It is well established that statistical properties of sequences are implicitly learned, and that these statistical properties correlate with changes in kinematic and speech behavior. For speech, this means that more predictable items are phonetically shorter. Accordingly, we hypothesized for glossolalia that if practitioners have learned a serial pattern in glossolalia in the same manner as in natural languages, its statistical properties should correlate with its phonetic characteristics. Our hypothesis was supported. We find significantly shorter syllables associated with higher syllable probabilities in glossolalia. We discuss this finding in relation to theories about the sources of probability-related changes in the speech signal.