Dataset Information

Apathy rating scores and β-amyloidopathy in patients with Parkinson disease at risk for cognitive decline.

ABSTRACT:

Objective

To determine whether β-amyloidopathy correlates with apathy rating scores independently of mood changes and other neurodegenerative processes in Parkinson disease (PD).

Methods

In this cross-sectional study, patients with PD (n = 64, 48 male and 16 female, mean age 69.2 ± 6.7 years, Hoehn & Yahr stage 2.7 ± 0.5, Montreal Cognitive Assessment score 25.3 ± 3.0) underwent [¹¹C]Pittsburgh compound B β-amyloid, [¹¹C]dihydrotetrabenazine vesicular monoamine transporter type 2 (VMAT2), and [¹¹C]methyl 4 piperidinyl propionate acetylcholinesterase brain PET imaging and clinical assessments, including the Marin Apathy Evaluation Scale, Clinician Version. Patients were recruited on the basis of having at least 1 risk factor for PD dementia, but they were excluded if they had dementia.

Results

Mean apathy rating score was 25.4 ± 6.4, reflecting predominantly subclinical apathy. Apathy rating scale scores correlated with amyloid binding, cognitive, depressive, and anxiety scores but not significantly with age, duration of disease, striatal VMAT2, or cholinergic binding. Multiple regression analysis model (p < 0.0001) showed significant regressor effects for global β-amyloid burden (p = 0.0038) with significant covariate effects for global cognitive z scores (p = 0.028) and for anxiety (p = 0.038) but not with depressive scores. Voxel-based analysis showed robust correlation between apathy rating scale scores and β-amyloid binding in bilateral nuclei accumbens, inferior frontal, and cingulate cortices (family-wise error rate-corrected p < 0.005).

Conclusion

Apathy is independently associated with β-amyloidopathy in patients with PD at risk of dementia. Regional brain findings are most robust for β-amyloidopathy in the nuclei accumbens, inferior frontal, and cingulate regions. Findings may provide an explanation for the often treatment-refractory nature of apathy in advancing PD despite optimized dopaminergic and antidepressant pharmacotherapy.

Clinicaltrialsgov identifier

NCT01565473.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC7079689 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceGenetic factors have a well-known influence on Parkinson disease (PD) susceptibility. The largest genome-wide association study (GWAS) identified 26 independent single-nucleotide polymorphisms (SNPs) associated with PD risk. Among patients, the course and severity of symptom progression is variable, and little is known about the potential association of genetic factors with phenotypic variance.ObjectiveTo assess whether GWAS-identified PD risk SNPs also have a cumulative association with the progression of cognitive and motor symptoms in patients with PD.Design, setting, and participantsThis longitudinal population-based cohort study of 285 patients of European ancestry with incident PD genotyped 23 GWAS SNPs. One hundred ninety-nine patients were followed up for a mean (SD) of 5.3 (2.1) years for progression (baseline: June 1, 2001, through November 31, 2007; follow-up: June 1, 2007, through August 31, 2013, with mortality surveillance through December 31, 2016); 57 patients had died or were too ill for follow-up, and 29 withdrew or could not be contacted. Movement disorder specialists repeatedly assessed PD symptom progression.Main outcomes measuresThe combined association of PD risk loci, after creating a weighted polygenic risk score (PRS), with cognitive decline, motor progression, and survival, relying on Cox proportional hazards regression models and inverse probability weights to account for censoring.ResultsOf the 285 patients undergoing genotyping, 160 were men (56.1%) and 125 were women (43.9%); the mean (SD) age at diagnosis was 69.1 (10.4) years. The weighted PRS was associated with significantly faster cognitive decline, measured by change in the Mini-Mental State Examination (hazard ratio [HR] per 1 SD, 1.44; 95% CI, 1.00-2.07). The PRS was also associated with faster motor decline, measured by time to Hoehn & Yahr Scale stage 3 (HR, 1.34; 95% CI, 1.00-1.79) and change in Unified Parkinson's Disease Rating Scale part III score (HR, 1.42; 95% CI, 1.00-2.01).Conclusions and relevanceSusceptibility SNPs for PD combined with a cumulative PRS were associated with faster motor and cognitive decline in patients. Thus, these genetic markers may be associated with not only PD susceptibility but also disease progression in multiple domains.

Project description:IntroductionRisk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia risk in older adults who do not have a history of CVD, and potential gender differences in this association, remains unclear. The aim of this study was to determine whether CVD risk scores are prospectively associated with cognitive decline and dementia in initially healthy older men and women.MethodsA total of19,114 participants from a prospective cohort of individuals aged 65+ years without known CVD or dementia were recruited. The atherosclerotic cardiovascular disease risk score (ASCVDRS), Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP), and the Framingham risk score (FRS) were calculated at baseline. Risk of dementia (according to DSM-IV criteria) and cognitive decline (defined as a >1.5 standard deviation decline in global cognition, episodic memory, psychomotor speed, or verbal fluency from the previous year) were assessed using hazard ratio.ResultsOver a median follow-up of 6.4 years, 850 individuals developed dementia and 4,352 cognitive decline. Men and women in the highest ASCVDRS tertile had a 41% (95% CI 1.08, 1.85) and 45% (1.11, 1.89) increased risk of dementia compared to the lowest tertile, respectively. Likewise, men and women in the highest SCORE2-OP tertile had a 64% (1.24, 2.16) and 60% (1.22, 2.11) increased risk of dementia compared to the lowest tertile, respectively. Findings were similar, but the risk was slightly lesser when examining risk of cognitive decline for both ASCVDRS and SCORE2-OP. However, FRS was only associated with the risk of cognitive decline among women (highest vs. lowest tertiles: 1.13 [1.01-1.26]).ConclusionThese findings suggest the utility of the ASCVDRS and SCORE2-OP in clinical practice, to not only assess future risk of CVD, but also as potential early indicators of cognitive impairment, even in relatively healthy older men and women.