Informant-Reported Cognitive Decline is Associated with Objective Cognitive Performance in Parkinson’s Disease

Author(s):  
Marina Z. Nakhla ◽  
Kelsey A. Holiday ◽  
J. Vincent Filoteo ◽  
Zvinka Z. Zlatar ◽  
Vanessa L. Malcarne ◽  
...  

Abstract Objective: The utility of informant-based measures of cognitive decline to accurately describe objective cognitive performance in Parkinson’s disease (PD) without dementia is uncertain. Due to the clinical relevance of this information, the purpose of this study was to examine the relationship between informant-based reports of patient cognitive decline via the Informant Questionnaire of Cognitive Decline in the Elderly (IQCODE) and objective cognition in non-demented PD controlling for cognitive status (i.e., mild cognitive impairment; PD-MCI and normal cognition; PD-NC). Method: One-hundred and thirty-nine non-demented PD participants (PD-MCI n = 38; PD-NC n = 101) were administered measures of language, executive function, attention, learning, delayed recall, visuospatial function, mood, and motor function. Each participant identified an informant to complete the IQCODE and a mood questionnaire. Results: Greater levels of informant-based responses of patient cognitive decline on the IQCODE were significantly associated with worse objective performance on measures of global cognition, attention, learning, delayed recall, and executive function in the overall sample, above and beyond covariates and cognitive status. However, the IQCODE was not significantly associated with language or visuospatial function. Conclusions: Results indicate that informant responses, as measured by the IQCODE, may provide adequate information on a wide range of cognitive abilities in non-demented PD, including those with MCI and normal cognition. Findings have important clinical implications for the utility of the IQCODE in the identification of PD patients in need of further evaluation, monitoring, and treatment.

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jacob D. Jones ◽  
Charles Jacobson ◽  
Martina Murphy ◽  
Catherine Price ◽  
Michael S. Okun ◽  
...  

Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinson’s disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity.Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables.Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinson’s Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function.Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated.


2021 ◽  
Vol 13 ◽  
Author(s):  
Megan C. Bakeberg ◽  
Anastazja M. Gorecki ◽  
Jade E. Kenna ◽  
Alexa Jefferson ◽  
Michelle Byrnes ◽  
...  

IntroductionCholesterol levels have been associated with age-related cognitive decline, however, such an association has not been comprehensively explored in people with Parkinson’s disease (PD). To address this uncertainty, the current cross-sectional study examined the cholesterol profile and cognitive performance in a cohort of PD patients.MethodsCognitive function was evaluated using two validated assessments (ACE-R and SCOPA-COG) in 182 people with PD from the Australian Parkinson’s Disease Registry. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and Triglyceride (TRG) levels were examined within this cohort. The influence of individual lipid subfractions on domain-specific cognitive performance was investigated using covariate-adjusted generalised linear models.ResultsFemales with PD exhibited significantly higher lipid subfraction levels (TC, HDL, and LDL) when compared to male counterparts. While accounting for covariates, HDL levels were strongly associated with poorer performance across multiple cognitive domains in females but not males. Conversely, TC and LDL levels were not associated with cognitive status in people with PD.ConclusionHigher serum HDL associates with poorer cognitive function in females with PD and presents a sex-specific biomarker for cognitive impairment in PD.


2021 ◽  
pp. 1-17
Author(s):  
Diego Santos García ◽  
Lucía García Roca ◽  
Teresa de Deus Fonticoba ◽  
Carlos Cores Bartolomé ◽  
Lucía Naya Ríos ◽  
...  

Background: Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective: Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods: PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes. Results: At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p < 0.0001; Coehn’s effect = –0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p = 0.250) (p = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= –0.1; 95% CI, –4.36 – –0.27; p = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 – 3.17; p = 0.045). Conclusion: Constipation is associated with cognitive decline in PD patients but not in controls.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Natália Pessoa Rocha ◽  
Paula Luciana Scalzo ◽  
Izabela Guimarães Barbosa ◽  
Mariana Soares Souza ◽  
Isabela Boechat Morato ◽  
...  

Cognitive impairment and depressive symptoms are of great interest in Parkinson’s disease (PD), since they are very common and lead to increased disability with poor quality of life. Inflammatory mechanisms have been implicated in PD and its nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels of chemokines in PD patients and to analyze the putative association of chemokines with depressive symptoms and cognitive performance. We hypothesized that higher chemokines levels are associated with worse cognitive performance and increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age- and gender-matched controls were subjected to a clinical evaluation including cognitive and mood tests. Peripheral blood was drawn and plasma levels of CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by enzyme-linked immunosorbent assay. PD patients and control individuals presented comparable plasma concentrations of all the evaluated chemokines. In PD patients, CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on cognitive tests. Although there was no significant difference between PD patients and control individuals regarding chemokines levels, our preliminary results showed that CXCL10/IP-10 may be associated with cognitive status in PD.


2013 ◽  
Vol 71 (12) ◽  
pp. 948-954
Author(s):  
Dannyel Barbirato ◽  
Alessandro Carvalho ◽  
Narahyana Bom de Araujo ◽  
Jose Vicente Martins ◽  
Andrea Deslandes

Objective To evaluate the relationship between the quantitative results of functional and cognitive performance of patients with Parkinson's disease (PD) and disease severity; and to study the relationship between patients' functional and cognitive capacity and motor impairment (Unified Parkinson's Disease Rating Scale - UPDRS III). Method Twenty-nine subjects clinically diagnosed with PD were classified into three groups according to disease severity using the modified Hoehn and Yahr Scale (H&Y). They were submitted to functional (Senior Fitness Test) and neuropsychological tests. Stepwise regression analysis showed a significant association between H&Y and upper limb strength (r 2 =0.30; p=0.005) and executive function (r 2 =0.37; p=0.004). In relation to UPDRS III, there was a significant association between lower limb strength (r 2 =0.27; p=0.010) and global cognitive status (r 2 =0.24; p=0.024). Conclusion The implementation of simple tests of functional capacity associated with neuropsychological testing can help to assess disease severity and motor impairment, and can be used to monitor the response to treatment in PD.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Megan C. Bakeberg ◽  
Anastazja M. Gorecki ◽  
Abigail L. Pfaff ◽  
Madison E. Hoes ◽  
Sulev Kõks ◽  
...  

AbstractThe translocase of outer mitochondrial membrane 40 (TOMM40) ‘523’ polymorphism has previously been associated with age of Alzheimer’s disease onset and cognitive functioning in non-pathological ageing, but has not been explored as a candidate risk marker for cognitive decline in Parkinson’s disease (PD). Therefore, this longitudinal study investigated the role of the ‘523’ variant in cognitive decline in a patient cohort from the Parkinson’s Progression Markers Initiative. As such, a group of 368 people with PD were assessed annually for cognitive performance using multiple neuropsychological protocols, and were genotyped for the TOMM40 ‘523’ variant using whole-genome sequencing data. Covariate-adjusted generalised linear mixed models were utilised to examine the relationship between TOMM40 ‘523’ allele lengths and cognitive scores, while taking into account the APOE ε genotype. Cognitive scores declined over the 5-year study period and were lower in males than in females. When accounting for APOE ε4, the TOMM40 ‘523’ variant was not robustly associated with overall cognitive performance. However, in APOE ε3/ε3 carriers, who accounted for ~60% of the whole cohort, carriage of shorter ‘523’ alleles was associated with more severe cognitive decline in both sexes, while carriage of the longer alleles in females were associated with better preservation of global cognition and a number of cognitive sub-domains, and with a delay in progression to dementia. The findings indicate that when taken in conjunction with the APOE genotype, TOMM40 ‘523’ allele length is a significant independent determinant and marker for the trajectory of cognitive decline and risk of dementia in PD.


2021 ◽  
Vol 64 (4) ◽  
pp. 66-68
Author(s):  
Olga Gavriliuc ◽  
◽  
Alexandru Andrusca ◽  
Lilian Popil ◽  
Mihail Gavriliuc ◽  
...  

Background: Before L-Dopa’s discovery, anticholinergic drugs were among the first treatments for Parkinson’s disease. Only now trihexyphenidyl (THP) is approved to treat unresponsive L-dopa tremors in young, cognitively unaffected Parkinson’s disease patients. However, there are no specific recommendations for disease duration, medication dose, or cognitive status. In low-income countries, THP is still frequently used in Parkinson’s disease patients with tremor. The objective of the current study was to evaluate cognitive performance in Parkinson’s disease patients receiving a low dose of THP. Material and methods: The study was performed on nineteen PD patients, nine of whom were on THP. All patients completed MoCA cognitive assessment. The patients were matched depending on their age, disease severity based on UPDRS III and duration of the disease. Results: The THP patients were taking an average dose of 3.3 mg of THP daily for an average of 1.8 years. There were no statistical differences between THP patients and non-THP patients in age (64.8± 4.8 vs 67.2±6.9, p=0.4), UPDRS III (32.1±8.9 vs 41.5±20.6, p=0.2) and disease duration (6.2±4.9 vs 7.0 ± 4.0, p=0.7). The THP patients had lower cognitive performance, with a total MoCA of 19.22 ± 3.3 vs. non-THP patients 24.2±3.0, p=0.003. Conclusions: In Parkinson’s disease patients, even a low dose of THP causes significant cognitive loss.


Author(s):  
Megan C. Bakeberg ◽  
Anastazja M. Gorecki ◽  
Jade E. Kenna ◽  
Alexa Jefferson ◽  
Michelle Byrnes ◽  
...  

Abstract Background Cognitive impairment is an important and diverse symptom of Parkinson’s disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been comprehensively investigated. Objectives This cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large PD cohort. Methods Cognitive function was evaluated using the Addenbrooke’s Cognitive Examination in 392 people with PD (PwP) from the Australian Parkinson’s Disease Registry. The influence of sex on domain-specific cognitive performance was investigated using covariate-corrected generalised linear models. In a repeated measures longitudinal subset of 127 PwP, linear mixed models were used to assess the impact of sex on cognition over time, while accounting for covariates. Results Cross-sectional-corrected modelling revealed that sex was significantly predictive of cognitive performance, with males performing worse than females on global cognition, and memory and fluency domains. Longitudinally, sex was significantly predictive of cognitive decline, with males exhibiting a greater reduction in global cognition and language, whereas females showed a greater decline in attention/orientation, memory and visuospatial domains, despite starting with higher baseline scores. At follow-up, a significantly higher proportion of males than females fulfilled criteria for mild cognitive impairment or PD dementia. Conclusions Sex was revealed as a significant determinant of overall cognitive performance as well as specific cognitive domains, with a differential pattern of decline in male and female participants. Such sex-specific findings appear to explain some of the heterogeneity observed in PD, warranting further investigation of mechanisms underlying this sexual dimorphism.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojuan Dan ◽  
Yang Hu ◽  
Junyan Sun ◽  
Linlin Gao ◽  
Yongtao Zhou ◽  
...  

Background: Cognitive impairment is one of the most prominent non-motor symptoms in Parkinson's disease (PD), due in part to known cerebellar dysfunctions. Furthermore, previous studies have reported altered cerebellar functional connectivity (FC) in PD patients. Yet whether these changes are also due to the cognitive deficits in PD remain unclear.Methods: A total of 122 non-dementia participants, including 64 patients with early PD and 58 age- and gender-matched elderly controls were stratified into four groups based on their cognitive status (normal cognition vs. cognitive impairment). Cerebellar volumetry and FC were investigated by analyzing, respectively, structural and resting-state functional MRI data among groups using quality control and quantitative measures. Correlation analysis between MRI metrics and clinical features (motor and cognitive scores) were performed.Results: Compared to healthy control subjects with no cognitive deficits, altered cerebellar FC were observed in early PD participants with both motor and cognitive deficits, but not in PD patients with normal cognition, nor elderly subjects showing signs of a cognitive impairment. Moreover, connectivity between the “motor” cerebellum and SMA was positively correlated with motor scores, while intracerebellar connectivity was positively correlated with cognitive scores in PD patients with cognitive impairment. No cerebellar volumetric difference was observed between groups.Conclusions: These findings show that altered cerebellar FC during resting state in early PD patients may be driven not solely by the motor deficits, but by cognitive deficits as well, hence highlighting the interplay between motor and cognitive functioning, and possibly reflecting compensatory mechanisms, in the early PD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sara Andersson ◽  
Maria Josefsson ◽  
Lars J. Stiernman ◽  
Anna Rieckmann

Cognitive impairment is an important symptom of Parkinson’s disease (PD) and predicting future cognitive decline is crucial for clinical practice. Here, we aim to identify latent sub-groups of longitudinal trajectories of cognitive change in PD patients, and explore predictors of differences in cognitive change. Longitudinal cognitive performance data from 349 newly diagnosed PD patients and 145 healthy controls from the Parkinson Progression Marker Initiative were modeled using a multivariate latent class linear mixed model. Resultant latent classes were compared on a number of baseline demographics and clinical variables, as well as cerebrospinal fluid (CSF) biomarkers and striatal dopamine transporter (DAT) density markers of neuropathology. Trajectories of cognitive change in PD were best described by two latent classes. A large subgroup (90%), which showed a subtle impairment in cognitive performance compared to controls but remained stable over the course of the study, and a small subgroup (10%) which rapidly declined in all cognitive performance measures. Rapid decliners did not differ significantly from the larger group in terms of disease duration, severity, or motor symptoms at baseline. However, rapid decliners had lower CSF amyloidß42 levels, a higher prevalence of sleep disorder and pronounced loss of caudate DAT density at baseline. These data suggest the existence of a distinct minority sub-type of PD in which rapid cognitive change in PD can occur uncoupled from motor symptoms or disease severity, likely reflecting early pathological change that extends from motor areas of the striatum into associative compartments and cortex.


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