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Influence of Striatal Dopamine, Cerebral Small Vessel Disease, and Other Risk Factors on Age-Related Parkinsonian Motor Signs.

ABSTRACT: OBJECTIVE:Parkinsonian motor signs are common and disabling in older adults without Parkinson's disease (PD), but its risk factors are not completely understood. We assessed the influence of striatal dopamine levels, cerebral small vessel disease, and other factors on age-related parkinsonian motor signs in non-PD adults. METHODS:Striatal dopamine transporter (DAT) binding was quantified via [11C]-CFT positron emission tomography in 87 neurologically intact adults (20-85 years, 57.47% female) with concurrent data on: Unified Parkinson's Disease Rating Scale motor (UPDRSm), white matter hyperintensities (WMH), and other risk factors (grip strength, vibratory sensitivity, cardio- and cerebro-vascular comorbidities). Sex-adjusted nonparametric models first estimated the associations of age, DAT, WMH, and other factors with UPDRSm; next, interactions of age by DAT, WMH, or other factors were tested. To quantify the influence of DAT, WMH, and other risk factors on the main association of age with UPDRSm, multivariable mediation models with bootstrapped confidence intervals (CI) were used. RESULTS:Older age, lower DAT, higher WMH, and worse risk factors significantly predicted worse UPDRSm (sex-adjusted p < .04 for all). DAT, but not WMH or other factors, positively and significantly interacted with age (p = .02). DAT significantly reduced the age-UPDRSm association by 30% (results of fully adjusted mediation model: indirect effect: 0.027; bootstrapped 95% CI: 0.0007, 0.074). CONCLUSIONS:Striatal dopamine appears to influence to some extent the relationship between age and parkinsonian signs. However, much of the variance of parkinsonian signs appears unexplained. Longitudinal studies to elucidate the multifactorial causes of this common condition of older age are warranted.

SUBMITTER: Rosano C

PROVIDER: S-EPMC7328193 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Influence of Striatal Dopamine, Cerebral Small Vessel Disease, and Other Risk Factors on Age-Related Parkinsonian Motor Signs.

Rosano Caterina C Metti Andrea L AL Rosso Andrea L AL Studenski Stephanie S Bohnen Nicolaas I NI

The journals of gerontology. Series A, Biological sciences and medical sciences 20200301 4

<h4>Objective</h4>Parkinsonian motor signs are common and disabling in older adults without Parkinson's disease (PD), but its risk factors are not completely understood. We assessed the influence of striatal dopamine levels, cerebral small vessel disease, and other factors on age-related parkinsonian motor signs in non-PD adults.<h4>Methods</h4>Striatal dopamine transporter (DAT) binding was quantified via [11C]-CFT positron emission tomography in 87 neurologically intact adults (20-85 years, 57 ...[more]

PMID: 31425570

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Project description:Objectivesto explore the association between cerebral small-vessel diseases (CSVDs) and motor symptoms in Parkinson's disease (PD).Methods137 PD patients were recruited into the study. Detailed motor symptoms, including tremor, rigidity, bradykinesia, and axial impairment, were evaluated using Unified Parkinson's disease Rating Scale (UPDRS). Non-motor symptoms, including cognition, anxiety, and depression, were evaluated using Montreal Cognitive Assessment (MoCA), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD). Brain MRI was used to assess the subtypes of CSVDs, including lacunes, enlarged perivascular spaces (EPVS), and white matter hyperintensities (WMH). WMH were furtherly divided into deep WMH (DWMH) and periventricular hyperintensities (PVH). The association between CSVDs and motor symptoms was analyzed. Patients were divided into the postural instability and gait disability (PIGD) group and non-PIGD group. Demographic, clinical and CSVDs variables were compared between the two groups.ResultsCSVDs subtypes were all detected in the participants with different prevalence rates and severity degrees. We found a close association between EPVS in basal ganglia and the tremor score (p = 0.032), and between DWMH in the frontal and occipital lobes and the axial motor score (p < 0.05) through the spearman and multivariate liner regression analysis. Compared with the non-PIGD group, the PIGD group demonstrated more serious cognitive impairment and DWMH in the frontal and occipital lobes (p < 0.05). The demographic characteristics and vascular risk factors of the PIGD group were not different from those of the non-PIGD group. Cognitive impairment and DWMH in the frontal lobe were identified to be independent risk factors of PIGD motor phenotype.ConclusionsWe identified a close association between the CSVDs and motor symptoms in PD and DWMH in the frontal lobe was a risk factor of PIGD motor phenotype, which supports the contribution of vascular pathology in PD.

Dataset Information

Influence of Striatal Dopamine, Cerebral Small Vessel Disease, and Other Risk Factors on Age-Related Parkinsonian Motor Signs.

Publications

Influence of Striatal Dopamine, Cerebral Small Vessel Disease, and Other Risk Factors on Age-Related Parkinsonian Motor Signs.

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