Purpose: Cognitive impairment is one of the most debilitating nonmotor symptoms in Parkinson disease (PD), and its presentation is heterogeneous. One proposed model to explain cognitive variability in PD is the dual-syndrome hypothesis. This hypothesis delineates two cognitive profiles, a "fronto-striatal" profile and a "posterior cortical" profile according to symptom presentation, associated motor phenotype, and risk for dementia. The current study examined the dual-syndrome hypothesis in individuals with idiopathic PD to evaluate the existence of these profiles, determine the association with the motor phenotype (tremor dominant vs. postural instability/gait disorder), and assess the relative risk for dementia.
Method: A retrospective examination was conducted using data from the Parkinson's Progression Markers Initiative database at baseline (within 2 years of diagnosis) and 5 years after baseline. Descriptive categorizations, cluster analyses, generalized linear mixed models, and logistic regressions were used to address the research questions.
Results: There was emerging evidence of cognitive profiles; however, these were not fully supported by cluster analyses. Baseline cognitive profile was associated with later motor phenotype, and as predicted, dementia risk was greatest in persons with baseline posterior cortical impairments.
Conclusion: The current results provide mixed support for the dual-syndrome hypothesis, with some evidence that the posterior cortical cognitive profile is associated with postural instability and gait disorder as well as greater dementia risk.
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Neural substrates underlying distinct dual cognitive syndromes in Parkinson's disease.
Eur J Neurol
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Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Background: A dual-syndrome hypothesis, which states the cognitive impairments in Parkinson's disease (PD) are attributable to frontostriatal dopaminergic dysregulation and cortical disturbance-each associated with attention/executive and memory/visuospatial dysfunction, respectively-has been widely accepted. This multisystem contribution also underlies highly heterogeneous progression rate to dementia.
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Association of Early fMRI Connectivity Alterations With Different Cognitive Phenotypes in Patients With Newly Diagnosed Parkinson Disease.
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January 2025
From the IRCCS Neuromed (M.I.D.B., G.L., S.P., A.C., A.B., G.F., P.P., D.B.), Pozzilli; Department of Human Neurosciences (A.O., G.L., C.P., S.P., M.C., F.D.A., S.B., R.M., G.B., A.C., A.B., G.F., P.P., D.B.), Sapienza University of Rome; Department of Microscopic and Ultrastructural Anatomy (G.V.), Campus Biomedico University of Rome; Department of Neuroscience (M.C.), Istituto Superiore di Sanità, Rome; and Cognitive and Motor Rehabilitation and Neuroimaging Unit (F.D.A.), IRCCS Fondazione Santa Lucia, Rome, Italy.
Background And Objectives: According to the dual syndrome hypothesis, patients with Parkinson disease (PD) with visuospatial deficits are more likely to progress to dementia, compared with patients with a prevalent dysexecutive syndrome. In this study, we aimed to investigate whether early connectivity changes in the dorsolateral prefrontal cortex (DLPFC) and the precuneus (PCun)-which are critical to fronto-executive and visuospatial functions, respectively-can identify distinct cognitive phenotypes in cognitively intact newly diagnosed patients with PD.
Methods: Newly diagnosed, drug-naïve patients with PD (≤2 years from clinical onset) with normal Montreal Cognitive Assessment (MoCA), were consecutively enrolled from our Movement Disorders Clinics in Italy.
An Examination of Cognitive Heterogeneity in Parkinson Disease: The Dual-Syndrome Hypothesis.
J Speech Lang Hear Res
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Department of Communicative Disorders and Sciences, University at Buffalo, NY.
Purpose: Cognitive impairment is one of the most debilitating nonmotor symptoms in Parkinson disease (PD), and its presentation is heterogeneous. One proposed model to explain cognitive variability in PD is the dual-syndrome hypothesis. This hypothesis delineates two cognitive profiles, a "fronto-striatal" profile and a "posterior cortical" profile according to symptom presentation, associated motor phenotype, and risk for dementia.
View Article and Find Full Text PDFLongitudinal follow up of data-driven cognitive subtypes in Parkinson's disease.
Brain Behav
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Faculty of Medicine, The University of Queensland Centre for Clinical Research, Herston, QLD, Australia.
Aim: The dual syndrome hypothesis proposes that there are two cognitive subtypes in Parkinson's disease (PD): a frontal subtype with executive/attention impairment and gradual cognitive decline, and a posterior-cortical subtype with memory/visuospatial deficits and rapid cognitive decline. We aimed to compare the rate of global cognitive decline between subtypes derived using data-driven methods and explore their longitudinal performance within specific cognitive domains to better understand the prognosis of each subtype.
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A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease.
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Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China.
The dichotomized brain system is a concept that was generalized from the 'dual syndrome hypothesis' to explain the heterogeneity of cognitive impairment, in which anterior and posterior brain systems are independent but partially overlap. The dopaminergic system acts on the anterior brain and is responsible for executive function, working memory, and planning. In contrast, the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.
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