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BACKGROUND: Patients with Parkinson's disease (PD) experience changes in behavior, personality, and cognition that can manifest even in the initial stages of the disease. Previous studies have suggested that mild behavioral impairment (MBI) should be considered an early marker of cognitive decline. However, the precise neurostructural underpinnings of MBI in early- to mid-stage PD remain poorly understood. OBJECTIVE: The aim was to explore the changes in white matter microstructure linked to MBI and mild cognitive impairment (MCI) in early- to mid-stage PD using diffusion magnetic resonance imaging (dMRI). METHODS: A total of 91 PD patients and 36 healthy participants were recruited and underwent anatomical MRI and dMRI, a comprehensive neuropsychological battery, and the completion of the Mild Behavioral Impairment-Checklist. Metrics of white matter integrity included tissue fractional anisotropy (FAt) and radial diffusivity (RDt), free water (FW), and fixel-based apparent fiber density (AFD). RESULTS: The connection between the left amygdala and the putamen was disrupted when comparing PD patients with MBI (PD-MBI) to PD-non-MBI, as evidenced by increased RDt (η2 = 0.09, P = 0.004) and both decreased AFD (η2 = 0.05, P = 0.048) and FAt (η2 = 0.12, P = 0.014). Compared to controls, PD patients with both MBI and MCI demonstrated increased FW for the connection between the left orbitofrontal gyrus (OrG) and the hippocampus (η2 = 0.22, P = 0.008), augmented RDt between the right OrG and the amygdala (η2 = 0.14, P = 0.008), and increased RDt (η2 = 0.25, P = 0.028) with decreased AFD (η2 = 0.10, P = 0.046) between the right OrG and the caudate nucleus. CONCLUSION: MBI is associated with abnormal microstructure of connections involving the orbitofrontal cortex, putamen, and amygdala. To our knowledge, this is the first assessment of the white matter microstructure in PD-MBI using dMRI. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Disfunción Cognitiva , Enfermedad de Parkinson , Sustancia Blanca , Humanos , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/complicaciones , Masculino , Femenino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Persona de Mediana Edad , Anciano , Disfunción Cognitiva/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Pruebas Neuropsicológicas , Imagen de Difusión por Resonancia Magnética/métodos , Amígdala del Cerebelo/patología , Amígdala del Cerebelo/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Putamen/diagnóstico por imagen , Putamen/patologíaRESUMEN
Parkinson's disease (PD) is characterized by overlapping motor, neuropsychiatric, and cognitive symptoms. Worse performance in one domain is associated with worse performance in the other domains. Commonality analysis (CA) is a method of variance partitioning in multiple regression, used to separate the specific and common influence of collinear predictors. We apply, for the first time, CA to the functional connectome to investigate the unique and common neural connectivity underlying the interface of the symptom domains in 74 non-demented PD subjects. Edges were modeled as a function of global motor, cognitive, and neuropsychiatric scores. CA was performed, yielding measures of the unique and common contribution of the symptom domains. Bootstrap confidence intervals were used to determine the precision of the estimates and to directly compare each commonality coefficient. The overall model identified a network with the caudate nucleus as a hub. Neuropsychiatric impairment accounted for connectivity in the caudate-dorsal anterior cingulate and caudate-right dorsolateral prefrontal-right inferior parietal circuits, while caudate-medial prefrontal connectivity reflected a unique effect of both neuropsychiatric and cognitive impairment. Caudate-precuneus connectivity was explained by both unique and shared influence of neuropsychiatric and cognitive symptoms. Lastly, posterior cortical connectivity reflected an interplay of the unique and common effects of each symptom domain. We show that CA can determine the amount of variance in the connectome that is unique and shared amongst motor, neuropsychiatric, and cognitive symptoms in PD, thereby improving our ability to interpret the data while gaining novel insight into networks at the interface of these symptom domains.
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Núcleo Caudado/fisiopatología , Corteza Cerebral/fisiopatología , Conectoma/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Red Nerviosa/fisiopatología , Enfermedad de Parkinson/fisiopatología , Anciano , Anciano de 80 o más Años , Síntomas Conductuales/diagnóstico por imagen , Síntomas Conductuales/etiología , Síntomas Conductuales/fisiopatología , Núcleo Caudado/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatologíaRESUMEN
The objective was to determine whether a history of traumatic brain injury (TBI) was associated with Parkinson's Disease (PD) and specific cognitive, motor, and neuropsychiatric symptoms. A cross-sectional cohort study of 120 participants aged 60-85 years old (48 females) were recruited (69 PD and 51 healthy controls). Assessments included demographic information, neuropsychological tests, a motor evaluation, neuropsychiatric questionnaires, and the Brain Injury Screening Questionnaire. A history of TBI or number of TBIs was not significantly related to an increased risk of developing PD or poorer motor scores on the United Parkinson Disease Rating Scale part 3. There was a significant negative correlation between number of TBI's and mean z-scores of global cognition (rs(69) = -0.338, p = 0.004), executive function (rs(69) = -0.251, p = 0.038), memory (rs(69) = -0.262, p = 0.029), and language (rs(69) = -0.245, p = 0.042), and a significant positive correlation on the Beck Depression Inventory II (rs(69) = 0.285, p = 0.018) and the Patient Health Questionnaire-9 (PHQ-9) (rs(69) = 0.326, p = 0.006) in the PD group only. In conclusion, a history of TBI was negatively associated with cognition and positively associated with depressive symptoms in patients with PD, but not with motor symptoms.
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Lesiones Traumáticas del Encéfalo/epidemiología , Disfunción Cognitiva/epidemiología , Depresión/epidemiología , Enfermedad de Parkinson/epidemiología , Anciano , Anciano de 80 o más Años , Alberta/epidemiología , Disfunción Cognitiva/etiología , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , RiesgoRESUMEN
BACKGROUND: The dual syndrome hypothesis of cognitive impairment in PD suggests that two cognitive profiles exist with distinct pathological mechanisms and a differential risk for further cognitive decline. How these profiles relate to network dysfunction has never been explicitly characterized. OBJECTIVE: First, to assess intranetwork functional connectivity while considering global connectivity, and second, to relate network connectivity with measures of the dysexecutive and posterior cortical profiles. METHODS: Eighty-two subjects with idiopathic PD and 37 age-matched controls underwent resting-state functional MRI and comprehensive neuropsychological assessment. Intranetwork and global connectivity was compared between groups. Measures of the dysexecutive and posterior cortical profiles were related to network connectivity while considering demographic and disease-related covariates. RESULTS: PD subjects show decreased connectivity within several cortical networks. However, only the sensorimotor network displayed a loss of connectivity independent of the observed decreased global connectivity. The dysexecutive factor was independently related to increased motor severity, less education, and decreased connectivity in the sensorimotor network. The posterior cortical factor was related to increased age, less education, decreased connectivity in the central executive network, as well as increased connectivity in the temporal network. CONCLUSIONS: Our results provide evidence supporting a network-specific process of degeneration in the sensorimotor network which contributes to the dysexecutive cognitive profile. In contrast, connectivity of the temporal and central executive network is related to the posterior cortical profile, representing a distinct network signature of this syndrome. © 2019 International Parkinson and Movement Disorder Society.
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Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Anciano , Mapeo Encefálico , Cognición/fisiología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Función Ejecutiva/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicologíaRESUMEN
BACKGROUND: Non-invasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation hold promise for inducing brain plasticity. However, their limited precision may hamper certain applications. In contrast, Transcranial Ultrasound Stimulation (TUS), known for its precision and deep brain targeting capabilities, requires further investigation to establish its efficacy in producing enduring effects for treating neurological and psychiatric disorders. OBJECTIVE: To investigate the enduring effects of different pulse repetition frequencies (PRF) of TUS on motor corticospinal excitability. METHODS: T1-, T2-weighted, and zero echo time magnetic resonance imaging scans were acquired from 21 neurologically healthy participants for neuronavigation, skull reconstruction, and the performance of transcranial ultrasound and thermal modelling. The effects of three different TUS PRFs (10, 100, and 1000 Hz) with a constant duty cycle of 10 % on corticospinal excitability in the primary motor cortex were assessed using TMS-induced motor evoked potentials (MEPs). Each PRF and sham condition was evaluated on separate days, with measurements taken 5-, 30-, and 60-min post-TUS. RESULTS: A significant decrease in MEP amplitude was observed with a PRF of 10 Hz (p = 0.007), which persisted for at least 30 min, and with a PRF of 100 Hz (p = 0.001), lasting over 60 min. However, no significant changes were found for the PRF of 1000 Hz and the sham conditions. CONCLUSION: This study highlights the significance of PRF selection in TUS and underscores its potential as a non-invasive approach to reduce corticospinal excitability, offering valuable insights for future clinical applications.
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Potenciales Evocados Motores , Corteza Motora , Humanos , Corteza Motora/fisiología , Corteza Motora/diagnóstico por imagen , Masculino , Potenciales Evocados Motores/fisiología , Método Doble Ciego , Femenino , Adulto , Estimulación Magnética Transcraneal/métodos , Adulto Joven , Imagen por Resonancia Magnética , Tractos Piramidales/fisiología , Tractos Piramidales/diagnóstico por imagen , Inhibición Neural/fisiologíaRESUMEN
INTRODUCTION: Brain atrophy in Parkinson's disease occurs to varying degrees in different brain regions, even at the early stage of the disease. While cortical morphological features are often considered independently in structural brain imaging studies, research on the co-progression of different cortical morphological measurements could provide new insights regarding the progression of PD. This study's aim was to examine the interplay between cortical curvature and thickness as a function of PD diagnosis, motor symptoms, and cognitive performance. METHODS: A total of 359 de novo PD patients and 159 healthy controls (HC) from the Parkinson's Progression Markers Initiative (PPMI) database were included in this study. Additionally, an independent cohort from four databases (182 PD, 132 HC) with longer disease durations was included to assess the effects of PD diagnosis in more advanced cases. Pearson correlation was used to determine subject-specific associations between cortical curvature and thickness estimated from T1-weighted MRI images. General linear modeling (GLM) was then used to assess the effect of PD diagnosis, motor symptoms, and cognitive performance on the curvature-thickness association. Next, longitudinal changes in the curvature-thickness correlation as well as the predictive effect of the cortical curvature-thickness association on changes in motor symptoms and cognitive performance across four years were investigated. Finally, Akaike information criterion (AIC) was used to build a GLM to model PD motor symptom severity cross-sectionally. RESULTS: A significant interaction effect between PD motor symptoms and age on the curvature-thickness correlation was found (ßstandardized = 0.11; t(350) = 2.12; p = 0.03). This interaction effect showed that motor symptoms in older patients were related to an attenuated curvature-thickness association. No significant effect of PD diagnosis was observed for the PPMI database (ß = 0.03; t(510) = 0.35; p = 0.72). However, in patients with a longer disease duration, a significant effect of diagnosis on the curvature-thickness association was found (ßstandardized = 0.31; t(306.7) = 3.49; p = 0.0006). Moreover, rigidity, but not tremor, in PD was significantly related to the curvature-thickness correlation (ßstandardized = 0.11, t(350) = 2.24, p = 0.03; ßstandardized = -0.03, t(350) = -0.58, p = 0.56, respectively). The curvature-thickness association was attenuated over time in both PD and HC, but the two groups did not show a significantly different effect (ßstandardized = 0.03, t(184.7) = 0.78, p = 0.44). No predictive effects of the CC-CT correlation on longitudinal changes in cognitive performance or motor symptoms were observed (all p-values > 0.05). The best cross-sectional model for PD motor symptoms included the curvature-thickness correlation, cognitive performance, and putamen dopamine transporter (DAT) binding, which together explained 14 % of variance. CONCLUSION: The association between cortical curvature and thickness is related to PD motor symptoms and age. This research shows the potential of modeling the curvature-thickness interplay in PD.
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Enfermedad de Parkinson , Humanos , Anciano , Enfermedad de Parkinson/metabolismo , Estudios Transversales , Encéfalo , Putamen/metabolismo , TemblorRESUMEN
Patients with Parkinson's Disease (PD) often suffer from cognitive decline. Accurate prediction of cognitive decline is essential for early treatment of at-risk patients. The aim of this study was to develop and evaluate a multimodal machine learning model for the prediction of continuous cognitive decline in patients with early PD. We included 213 PD patients from the Parkinson's Progression Markers Initiative (PPMI) database. Machine learning was used to predict change in Montreal Cognitive Assessment (MoCA) score using the difference between baseline and 4-years follow-up data as outcome. Input features were categorized into four sets: clinical test scores, cerebrospinal fluid (CSF) biomarkers, brain volumes, and genetic variants. All combinations of input feature sets were added to a basic model, which consisted of demographics and baseline cognition. An iterative scheme using RReliefF-based feature ranking and support vector regression in combination with tenfold cross validation was used to determine the optimal number of predictive features and to evaluate model performance for each combination of input feature sets. Our best performing model consisted of a combination of the basic model, clinical test scores and CSF-based biomarkers. This model had 12 features, which included baseline cognition, CSF phosphorylated tau, CSF total tau, CSF amyloid-beta1-42, geriatric depression scale (GDS) scores, and anxiety scores. Interestingly, many of the predictive features in our model have previously been associated with Alzheimer's disease, showing the importance of assessing Alzheimer's disease pathology in patients with Parkinson's disease.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Parkinson , Humanos , Anciano , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/líquido cefalorraquídeo , Enfermedad de Alzheimer/complicaciones , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/líquido cefalorraquídeo , Cognición , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Progresión de la EnfermedadRESUMEN
Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by later life emergence of sustained neuropsychiatric symptoms, as an at-risk state for incident cognitive decline and dementia. Prior studies have reported that neuropsychiatric symptoms are associated with cognitive abilities in Parkinson's disease (PD) patients, and we have recently found a strong correlation between MBI and cognitive performance. However, the underlying neural activity patterns of cognitive performance linked to MBI in PD are unknown. Fifty-nine non-demented PD patients and 26 healthy controls were scanned using fMRI during performance of a modified version of the Wisconsin card sorting task. MBI was evaluated using the MBI-checklist, and PD patients were divided into two groups, PD-MBI and PD-noMBI. Compared to the PD-noMBI group and healthy controls, the PD-MBI group revealed less activation in the prefrontal and posterior parietal cortices, and reduced deactivation in the medial temporal region. These results suggest that in PD, MBI reflects deficits in the frontoparietal control network and the hippocampal memory system.
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Disfunción Cognitiva , Enfermedad de Parkinson , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Humanos , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Enfermedad de Parkinson/diagnóstico por imagen , Lóbulo TemporalRESUMEN
Patients with Parkinson's disease (PD) have difficulties processing action words, which could be related to early cognitive decline. The action fluency test can be used to quickly and easily assess the processing of action words in PD. The goal of this study was to characterize how the action fluency test relates to personal characteristics, disease factors, cognition, and neural activity in PD. Forty-eight participants with PD (34 male, 14 female) and 35 control participants (16 male, 19 female) completed functional neuroimaging using a set-shifting task and a neuropsychological assessment including the action fluency test. PD participants with a score one standard deviation below the norm or lower on the action fluency test were identified. All PD participants with poor performance (PD-P, n = 15) were male. They were compared to male PD participants with scores within the normal range (PD-N, n = 19) and male healthy controls (HC, n = 16). PD-P were older, had lower global cognition scores, lower executive functions scores, and decreased activity in fronto-temporal regions compared with PD-N. There was no difference between the two PD groups in terms of the duration of the disease, dose of dopaminergic medication, and severity of motor symptoms. PD-N were younger than HC, but there was no other significant difference between these groups. The action fluency test identified a subgroup of PD patients with distinct sex, age, global cognition, executive functions, and brain activity characteristics. Implications for the evaluation of cognition are discussed.
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Función Ejecutiva , Enfermedad de Parkinson , Encéfalo/diagnóstico por imagen , Cognición , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicacionesRESUMEN
Cognitive impairments are prevalent in Parkinson's disease (PD), but the underlying mechanisms of their development are unknown. In this study, we aimed to predict global cognition (GC) in PD with machine learning (ML) using structural neuroimaging, genetics and clinical and demographic characteristics. As a post-hoc analysis, we aimed to explore the connection between novel selected features and GC more precisely and to investigate whether this relationship is specific to GC or is driven by specific cognitive domains. 101 idiopathic PD patients had a cognitive assessment, structural MRI and blood draw. ML was performed on 102 input features including demographics, cortical thickness and subcortical measures, and several genetic variants (APOE, MAPT, SNCA, etc.). Using the combination of RRELIEFF and Support Vector Regression, 11 features were found to be predictive of GC including sex, rs894280, Edinburgh Handedness Inventory, UPDRS-III, education, five cortical thickness measures (R-parahippocampal, L-entorhinal, R-rostral anterior cingulate, L-middle temporal, and R-transverse temporal), and R-caudate volume. The rs894280 of SNCA gene was selected as the most novel finding of ML. Post-hoc analysis revealed a robust association between rs894280 and GC, attention, and visuospatial abilities. This variant indicates a potential role for the SNCA gene in cognitive impairments of idiopathic PD.
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Trastornos del Conocimiento/genética , Disfunción Cognitiva/genética , Aprendizaje Automático , Enfermedad de Parkinson/genética , alfa-Sinucleína/genética , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , NeuroimagenRESUMEN
BACKGROUND: Mild behavioral impairment (MBI) is a syndrome characterized by later life onset, sustained neuropsychiatric symptoms as a marker of dementia risk. In Parkinson's disease (PD), MBI has been associated with worse cognitive abilities and increased cortical atrophy. However, the circuit level correlates of MBI have not been investigated in this population. Our objective was to investigate the relationship between MBI and corticostriatal connectivity in PD patients. This emphasis on corticostriatal connectivity was due to the significant role of these circuits in neuropsychiatric and cognitive symptoms across disease conditions. METHODS: Seventy-four non-demented patients with PD were administered the MBI-checklist, and classified as having high MBI (PD-MBI; n = 21) or low MBI scores (PD-noMBI; n = 53). Corticostriatal connectivity was assessed with both an atlas and seed-based analysis. The atlas analysis consisted of calculating the average connectivity between the striatal network and the default mode (DMN), central executive (CEN), and saliency networks (SAN). Structural measurements of cortical thickness and volume were also assessed. PD-MBI and PD-noMBI patients were compared, along with a group of age matched healthy control subjects (HC; n = 28). Subsequently, a seed analysis assessed the relationship of MBI scores with the connectivity of twelve seeds within the striatum while controlling for cognitive ability. A complementary analysis assessed the relationship between striatal connectivity and cognition, while controlling for MBI-C. RESULTS: PD-MBI demonstrated decreased connectivity between the striatum and both the DMN and SAN compared to PD-noMBI and HC. The decreased connectivity between the striatum and the SAN was explained partly by increased atrophy within the SAN in PD-MBI. The seed analysis revealed a relationship between higher MBI scores and lower connectivity of the left caudate head to the dorsal anterior cingulate cortex and left middle frontal gyrus. Higher MBI-C scores were also related to decreased connectivity of the right caudate head with the anterior cingulate cortex, precuneus, and left supramarginal gyrus, as well as increased connectivity to the left hippocampus and right cerebellar hemisphere. Caudate-precuneus connectivity was independently associated with both global behavioural and cognitive scores. CONCLUSION: These results suggest PD-MBI is associated with altered corticostriatal connectivity, particularly between the head of the caudate and cortical regions associated with the DMN and SAN. In particular, caudate-precuneus connectivity is associated with both global behavioral and cognitive symptoms in PD.
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Encéfalo/fisiopatología , Trastornos Mentales/fisiopatología , Vías Nerviosas/fisiopatología , Enfermedad de Parkinson/fisiopatología , Anciano , Mapeo Encefálico/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Trastornos Mentales/etiología , Enfermedad de Parkinson/complicacionesRESUMEN
Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD) and have demonstrated an association with the p. Val66Met, a polymorphism in the BDNF gene. Mild behavioral impairment (MBI) is a validated syndrome describing emergent and persistent NPS in older adults as a marker of potential cognitive decline and dementia. This study investigated if PD patients with the Met allele were more likely to have MBI and whether they had impairments in specific domains of MBI using the Mild Behavioral Impairment Checklist (MBI-C) as the MBI ascertainment tool. One hundred forty-six PD patients were screened for neuropsychiatric and cognitive impairments with the MBI-C and the Montreal Cognitive Assessment (MoCA). All participants were genotyped for the BDNF p.Val66Met single-nucleotide polymorphism (SNP) using TaqMan Genotyping Assay. Statistical analysis was performed using multiple linear and logistic regression models. Met carriers had a 2 times higher likelihood of being MBI positive (MBI-C total score ≥8) than Val carriers. Met carriers had significantly higher MBI-C total scores and significantly greater impairments in the mood/anxiety and the psychotic domains of MBI-C compared to Val carriers. These findings indicate that the BDNF Met allele is associated with a higher neuropsychiatric burden in PD.
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Background: Mild cognitive impairment is a common non-motor symptom of Parkinson's disease (PD-MCI) and has minimal treatment options. Objective: In this double-blind, randomized, sham-controlled trial, we assessed the effect of repeated sessions of intermittent theta-burst stimulation over the left dorsolateral prefrontal cortex on cognition and brain connectivity in subjects with PD-MCI. Methods: Forty-one subjects were randomized to receive real (n = 21) or sham stimulation (n = 20). All subjects underwent neuropsychological assessments before, 1 day, and 1 month after stimulation. Subjects also underwent resting-state functional magnetic resonance imaging before and 48 h after stimulation. The primary outcome was the change in the cognitive domain (executive function, attention, memory, language, and visuospatial abilities) z-scores across time. Results: There was an insignificant effect on cognitive domain z-scores across time when comparing real with sham stimulation and correcting for multiple comparisons across cognitive domains (p > 0.05 Bonferroni correction). However, the real stimulation group demonstrated a trend toward improved executive functioning scores at the 1-month follow-up compared with sham (p < 0.05 uncorrected). After real stimulation, the connectivity of the stimulation site showed decreased connectivity to the left caudate head. There was no change in connectivity within or between the stimulation network (a network of cortical regions connected to the stimulation site) and the striatal network. However, higher baseline connectivity between the stimulation network and the striatal network was associated with improved executive function scores at 1 month. Conclusions: These results suggest that intermittent theta-burst stimulation over the dorsolateral prefrontal cortex in subjects with PD-MCI has minimal effect on cognition compared with sham, although there were trends toward improved executive function. This intervention may be more effective in subjects with higher baseline connectivity between the stimulation network and the striatal network. This trial supports further investigation focusing on executive function and incorporating connectivity-based targeting. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03243214.
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OBJECTIVE: To evaluate the associations of mild behavioral impairment (MBI) with cognitive deficits and patterns of gray matter changes in Parkinson disease (PD). METHODS: Sixty patients with PD without dementia and 29 healthy controls underwent a cognitive neuropsychological evaluation and structural MRI scan. MBI was evaluated with the MBI Checklist (MBI-C), a rating scale designed to elicit emergent neuropsychiatric symptoms in accordance with MBI criteria. We divided the patients with PD into 2 groups: 1 group with high MBI-C scores (PD-MBI) and the other with low MBI-C scores (PD-noMBI). RESULTS: Among 60 patients with PD, 20 were categorized as having PD-MBI (33.33%). In healthy controls, no participants met the MBI cut-point threshold. The PD-MBI group had significantly lower Montreal Cognitive Assessment and z scores in all 5 domains and the global score compared to healthy controls and those with PD-noMBI. In addition, all cognitive domains except language and global cognition negatively correlated with the MBI-C total score in all patients with PD. For cortical structures, the PD-MBI group revealed middle temporal cortex thinning and decreased volume compared with the PD-noMBI group, and decreased volume in this area negatively correlated with the MBI-C total score. CONCLUSIONS: The impaired cognitive function over all domains and atrophy in the temporal area in the PD-MBI group are in line with posterior cortical circuit deficits in PD, which have been associated with a faster rate of progression to dementia. These initial results suggest that MBI might be an early and important marker for incident cognitive decline and dementia in patients with PD.
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Disfunción Cognitiva/patología , Sustancia Gris/patología , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/psicología , Problema de Conducta/psicología , Lóbulo Temporal/patología , Anciano , Anciano de 80 o más Años , Atrofia/patología , Estudios de Casos y Controles , Disfunción Cognitiva/complicaciones , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicacionesRESUMEN
INTRODUCTION: Cognitive impairment can occur in the early phase of Parkinson's disease and increases the risk of developing dementia. Cognitive deficits were shown to be associated with functional alterations in the dorsolateral prefrontal cortex (DLPFC) and caudate nucleus. Two previous transcranial magnetic stimulation studies over the left DLPFC showed short-term improvement in cognitive performance and focused on specific task. METHODS: 28 patients with idiopathic Parkinson's disease and mild cognitive impairment received intermittent "theta burst" stimulation (iTBS) (active, Nâ¯=â¯14; or sham, Nâ¯=â¯14) over the left DLPFC, twice a day for three days with 1-2 days in between. Detailed neuropsychological assessment of five cognitive domains was performed before iTBS and on days 1, 10, and 30 after the last iTBS session. Composite Z-scores were calculated for each domain and for overall cognition. RESULTS: Our results showed an increase in overall cognition up to one month in both groups but this effect was only significant in the active group. Improvements were seen in the attention domain for both groups and in the visuospatial domain in the active group only. No significant differences were found between the groups. CONCLUSION: These preliminary findings suggest that active iTBS might improve overall cognitive performance in patients with Parkinson's disease with mild cognitive impairment and that this effect can last up to one month. This cognitive improvement, is likely mediated by improvement on visuospatial abilities. Further studies are needed to explore the potential of iTBS as a therapeutical tool to slow cognitive decline in patients with Parkinson's disease.
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Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Estimulación Magnética Transcraneal/métodos , Anciano , Cognición/fisiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Are self-report measures of prospective memory (ProM) reliable and valid? To examine this question, 240 undergraduate student volunteers completed several widely used self-report measures of ProM including the Prospective Memory Questionnaire (PMQ), the Prospective and Retrospective Memory Questionnaire (PRMQ), the Comprehensive Assessment of Prospective Memory (CAPM) questionnaire, self-reports of retrospective memory (RetM), objective measures of ProM and RetM, and measures of involvement in activities and events, memory strategies and aids use, personality and verbal intelligence. The results showed that both convergent and divergent validity of ProM self-reports are poor, even though we assessed ProM using a newly developed, reliable continuous measure. Further analyses showed that a substantial proportion of variability in ProM self-report scores was due to verbal intelligence, personality (conscientiousness, neuroticism), activities and event involvement (busyness), and use of memory strategies and aids. ProM self-reports have adequate reliability, but poor validity and should not be interpreted as reflecting ProM ability.