Cerebral white matter hyperintensity in Parkinson's disease: A major risk factor for mild cognitive impairment

BackgroundMild cognitive impairment (MCI) and dementia contribute to a poor quality of life among patients with PD. The influence of cerebral ischemia as a risk factor for MCI in PD has not been adequately investigated. To address this issue, we examined the influence of the volume and distribution of white matter hyperintensity (WMH) as a risk factor for MCI in early PD.MethodsProspective study of patients with early idiopathic PD. All patients had baseline MRI-FLAIR, clinical assessment and detailed neuropsychological evaluation. Data on demographics, vascular risk factors, cognitive performance and WMH volumes were analyzed.Results91 patients; mean age 64.9 years, mean education of 10.5 years. 24 patients fulfilled the Movement Disorder Society criteria for MCI and were classified as PD-MCI while the rest were classified as PD with no cognitive impairment (PD-NCI). Patients with PD-MCI and PD-NCI did not differ in Hoehn & Yahr staging. PD-MCI patients had a higher prevalence of diabetes mellitus, hypertension and hyperlipidemia. PD-MCI patients had significantly greater volume of periventricular (6.04 ml vs. 2.66 ml, p = 0.001) and deep subcortical WMH (2.16 vs.1.44, p = 0.002). Regional WMH was significantly greater among PD-MCI in the frontal, parietal and occipital regions. Logistic regression analyses demonstrated WMH to be associated with PD-MCI independent of age, education, and vascular risk factors. Increasing WMH volume was associated with lower performance on executive function, memory and language.ConclusionsWMH is an important risk factor for PD-MCI independent of vascular risk factors. PD patients with WMH should be regularly screened for MCI.     

NREM sleep arousal-related disorders reflect cognitive impairment in Parkinson's disease

BackgroundSleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders.Objectives: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD.MethodsClinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54).ResultsArousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387–95% CI 1.395–8.220, p = 0.007).ConclusionArousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach.     

Montreal Cognitive Assessment for the screening and prediction of cognitive decline in early Parkinson's disease

BackgroundEarly diagnosis of cognitive impairment in PD would allow appropriate monitoring and timely intervention to reduce the progression to dementia (PDD).ObjectiveTo study the usefulness of the Montreal Cognitive Assessment (MoCA) in the screening for mild cognitive impairment (PD-MCI) and its predictive utility in determining longitudinal cognitive decline in PD.MethodsProspective longitudinal study of patients with mild PD. PD-MCI and PDD was diagnosed based on the Movement Disorder taskforce (MDS) criteria. Receiver Operating Characteristic analyses and Cox regression analyses were performed.Results95 patients; mean age 66.37 (SD 7.86); mean H&Y score of 1.99 (SD 0.45) were studied. At baseline, 34 patients fulfilled the MDS criteria for PD-MCI. MoCA, compared to the MMSE had a high discriminatory power in detecting PD-MCI [Area Under Curve (AUC) of 0.912, p < 0.001]. A MoCA score of ≤26 provided a sensitivity of 93.1% for the diagnosis of PD-MCI. In the longitudinal cohort over 2 years, baseline MOCA was useful in predicting cognitive decline (AUC of 0.707, p = 0.05). With Cox regression analyses, a 1-point lower score on baseline MoCA was associated with a 34% increased risk of cognitive decline [Hazard ratio (HR) 1.34; 95% CI: 1.03–1.74: p = 0.029]. A baseline MoCA ≤26 was highly predictive of progressive cognitive decline (HR 3.47, 95% CI: 2.38–5.07; p < 0.01).ConclusionsMoCA is a reliable tool in predicting cognitive decline in early PD. A MoCA score of ≤26 significantly increases the risk for progressive cognitive decline.     

Dissociations among daytime sleepiness,nighttime sleep,and cognitive status in Parkinson's disease

BackgroundDaytime and nighttime sleep disturbances and cognitive impairment occur frequently in Parkinson's disease (PD), but little is known about the interdependence of these non-motor complications. Thus, we examined the relationships among excessive daytime sleepiness, nighttime sleep quality and cognitive impairment in PD, including severity and specific cognitive deficits.MethodsNinety-three PD patients underwent clinical and neuropsychological evaluations including the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD) using recently proposed Movement Disorder Society PD-MCI and PDD criteria. Relationships between the sleep and cognitive measures and PD cognitive groups were examined.ResultsThe PD cohort included PD-NC (n = 28), PD-MCI (n = 40), and PDD (n = 25) patients. ESS scores, as a measure of daytime sleepiness, were significantly worse (p = 0.005) in cognitively impaired PD patients, particularly PDD patients. ESS scores correlated significantly with Mini-Mental State Examination scores and also with cognitive domain scores for attention/working memory, executive function, memory, and visuospatial function. In contrast, PSQI scores, as a measure of nighttime sleep quality, neither differed among cognitive groups nor correlated with any cognitive measures.ConclusionsDaytime sleepiness in PD, but not nighttime sleep problems, is associated with cognitive impairment in PD, especially in the setting of dementia, and attention/working memory, executive function, memory, and visuospatial deficits. The presence of nighttime sleep problems is pervasive across the PD cognitive spectrum, from normal cognition to dementia, and is not independently associated with cognitive impairment or deficits in cognitive domains.     

Cognitive impairment in Parkinson's disease is associated with Default Mode Network subsystem connectivity and cerebrospinal fluid Aβ

IntroductionTo identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis.MethodsIn this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments.ResultsLHC-RHC (F_3,67 = 3.41,p=0.023) and CSF Aβ-42:40 (χ²(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment.ConclusionWe used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.     

The Penn Parkinson's Daily Activities Questionnaire-15: Psychometric properties of a brief assessment of cognitive instrumental activities of daily living in Parkinson's disease

IntroductionTo describe the psychometric properties of the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15), a 15-item measure of cognitive instrumental activities of daily living for Parkinson's disease (PD) patients derived from the original 50-item PDAQ.MethodsPDAQ-15 items were chosen by expert consensus. Knowledgeable informants of PD participants (n = 161) completed the PDAQ-15. Knowledgeable informants were defined as an individual having regular contact with the PD participant. PD participants were assigned a diagnosis of normal cognition, mild cognitive impairment, or dementia based on expert consensus.ResultsPDAQ-15 scores correlated strongly with global cognition (Dementia Rating Scale-2, r = 0.71, p < 0.001) and a performance-based functional measure (Direct Assessment of Functional Status, r = 0.83; p < 0.001). PDAQ-15 scores accurately discriminated between non-demented PD participants (normal cognition/mild cognitive impairment) and PD with dementia (ROC curve area = 0.91), participants with and without any cognitive impairment (normal cognition versus mild cognitive impairment/dementia, ROC curve area = 0.85) and between participants with mild cognitive impairment and dementia (ROC curve area = 0.84).ConclusionsThe PDAQ-15 shows good discriminant validity across cognitive stages, correlates highly with global cognitive performance, and appears suitable to assess daily cognitive functioning in PD.     

Impaired financial abilities in Parkinson's disease patients with mild cognitive impairment and dementia

PurposeFinancial capacity (FC) is an instrumental activity of daily living (IADL) critical to independent functioning and sensitive to cognitive impairment in dementia. Little is known about FC in cognitively impaired patients with Parkinson's disease (PD). The present study investigated FC in PD patients with prodromal and clinical dementia.MethodsParticipants were 20 older controls and 35 PD patients who met consensus criteria for either mild cognitive impairment (PD-MCI, n = 18) or PD dementia (PDD, n = 17). FC was assessed using a standardized performance based measure consisting of 9 domain and two global scores (Financial Capacity Instrument; FCI) (1). FCI domain and global performance scores were compared across groups. Capacity impairment ratings (no impairment, mild/moderate impairment, severe impairment) were calculated for each PD patient's domain and global scores.ResultsRelative to controls, PD-MCI patients were impaired on both FCI global scores and domains of basic monetary skills, financial concepts, and investment decision-making. Relative to both controls and PD-MCI patients, PDD patients were impaired on virtually all FCI variables. With respect to impairment ratings, greater than 50% of PD-MCI patients and greater than 90% of PDD patients were classified as either mild/moderate or severely impaired on the two FCI global scores.ConclusionsImpairment of financial capacity is already present in PD-MCI and is advanced in PDD. Complex cognitively-mediated IADLs such as financial capacity appear to be impaired early in the course of PD dementia.     

Subcortical grey matter changes in untreated,early stage Parkinson's disease without dementia

BackgroundPrevious MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage.MethodsWe recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively.ResultsVoxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity.ConclusionsOur results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients.     

Association between homocysteine and third ventricle dilatation,mesencephalic area atrophy in Parkinson’s disease with cognitive impairment

ObjectivesThis study aimed to explore the association of homocysteine (Hcy) with third ventricle (V3) dilatation and mesencephalic area (MA) atrophy as determined by transcranial sonography (TCS) in Parkinson’s disease (PD) with cognitive impairment.MethodsThe final statistical analysis included 101 PD patients and 20 age- and sex-matched controls. Using the Movement Disorder Society (MDS) level II criteria for PD with cognitive impairment, we categorized the PD patients into PD with normal cognition group (PD) and PD with cognitive impairment group (PDC). All subjects underwent TCS and laboratory analysis.ResultsThe V3 width (r = 0.349, P = 0.005) and the MA (r = −0.484, P < 0.001) were significantly correlated with the Hcy concentration in the PDC patients. Binary logistic regression analysis revealed that age (OR [95% CI] = 1.114 [0.991–1.251], P = 0.002), and Hcy level (OR [95% CI] = 0.931 [0.752–1.153], P = 0.411) were independent risk factors for V3 dilatation. Hcy level (OR [95% CI] = 0.557 [0.323–0.967], P = 0.035) were independent risk factors for MA atrophy. After adjustment for confounding factors, the odds ratio of V3 dilatation was 3.50 (95% CI 1.054–11.399, P = 0.031) and the odds ratio of MA atrophy was 4.67 (95% CI 1.395–15.602, P = 0.012) in the patients with higher Hcy level compared with the lower level.ConclusionsThe results revealed a close association between the V3 width, MA and Hcy concentration in PD patients with cognitive impairment. We hypothesized that increased Hcy concentration played a significant role in the development of brain atrophy in PD with cognitive impairment.     

Patterns of diffusion kurtosis changes in Parkinson's disease subtypes

BackgroundDiffusion kurtosis imaging has been applied to evaluate white matter and basal ganglia microstructure in mixed Parkinson's disease (PD) groups with inconclusive results.ObjectivesTo evaluate specific patterns of kurtosis changes in PD and to assess the utility of diffusion imaging in differentiating between healthy subjects and cognitively normal PD, and between PD with and without mild cognitive impairment.MethodsDiffusion scans were obtained in 92 participants using 3T MRI. Differences in white matter were tested by tract-based spatial statistics. Gray matter was evaluated in basal ganglia, thalamus, hippocampus, and motor and premotor cortices. Brain atrophy was also assessed. Multivariate logistic regression was used to identify a combination of diffusion parameters with the highest discrimination power between groups.ResultsDiffusion kurtosis metrics showed a significant increase in substantia nigra (p = 0.037, Hedges' g = 0.89), premotor (p = 0.009, Hedges' g = 0.85) and motor (p = 0.033, Hedges' g = 0.87) cortices in PD with normal cognition compared to healthy participants. Combined diffusion markers in gray matter reached 81% accuracy in differentiating between both groups. Significant white matter microstructural changes, and kurtosis decreases in the cortex were present in cognitively impaired versus cognitively normal PD. Diffusion parameters from white and gray matter differentiated between both PD phenotypes with 78% accuracy.ConclusionsIncreased kurtosis in gray matter structures in cognitively normal PD reflects increased hindrance to water diffusion caused probably by alpha-synuclein-related microstructural changes. In cognitively impaired PD, the changes are mostly driven by decreased white matter integrity. Our results support the utility of diffusion kurtosis imaging for PD diagnostics.     

Severity of mild cognitive impairment in early Parkinson's disease contributes to poorer quality of life

BackgroundPoor quality of life (QoL) is a feature of people with Parkinson's disease (PD) who develop dementia. The relationship between mild cognitive impairment in PD (PD-MCI) and QoL is less clear. To address this, we studied the impact of varying severities of cognitive impairment on QoL in a cohort of non-demented patients with early PD.MethodPatients with newly diagnosed PD (n = 219) and age and sex matched healthy controls (n = 99) completed a schedule of neuropsychological tests, in addition to scales assessing QoL (PDQ-39), depression, sleep, neuropsychiatric symptoms and a clinical examination. The Movement Disorder Society criteria were used to define and classify PD-MCI.ResultsParticipants with PD-MCI were significantly older than those with normal cognition, had more severe motor symptoms, scored higher for depression and had poorer quality of life. Logistic regression showed that mild cognitive impairment, independent of other factors, was an indicator of poorer QoL. Using cognitive performance 2.0 standard deviations (SD) below normative data as a cut-off to define PD-MCI, there was a significant difference in QoL scores between patients with PD-MCI and those classified as having normal cognition. Subjects with less severe mild cognitive impairment did not exhibit significant differences in QoL.ConclusionsPD-MCI is a significant, independent factor contributing to poorer QoL in patients with newly diagnosed PD. Those classified with greatest impairment (2.0 SD below normal values) have lower QoL. This has implications for clinical practice and future interventions targeting cognitive impairments.     

Cognitive impairment is associated with Hoehn and Yahr stages in early,de novo Parkinson disease patients

IntroductionThe relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages.MethodsForty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II.ResultsPatients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p = 0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p < 0.0001), 10 points Clock Drawing Test (p = 0.002), and Rey-Osterrieth Complex Figure Test -copy (p < 0.0001). ORs of having cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II.ConclusionIn de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI.     

A predictive model of neurodegeneration in idiopathic REM-sleep behavior disorder

ObjectiveTo investigate whether Parkinson's disease (PD) and dementia are competing risks in subjects with idiopathic rapid-eye-movement sleep behavior disorder (RBD).MethodsThe number of incidental PD cases observed in 11 longitudinal RBD studies was compared with the corresponding expected number as estimated by a simple mathematical model based on population parameters for PD age-of-onset.ResultsThe expected number of incidental PD cases exceeded observed PD cases (p-value < 0.001) but was in agreement with the sum of observed PD cases and observed mild cognitive impairment/dementia cases (p-value = 0.34). Sensitivity analyses confirmed the results.ConclusionIn the RBD population, PD and dementia cases are competing risks, suggesting that alpha-synuclein pathology occurs simultaneously in substantia nigra and neocortex. This observation has implications for the design and analysis of trials of neuroprotection.     

Pre-existing brain damage and association between severity and prior cognitive impairment in ischemic stroke patients

BackgroundWe evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS).MethodsIS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity.ResultsAmong the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages.ConclusionImpaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage.     

The interlocking finger test in patients with Parkinson’s disease and healthy subjects

The interlocking finger test (ILFT) is a bedside screening test in which the subject must imitate four bimanual finger gestures without symbolic meaning. We assessed the utility of the test in the cognitive evaluation of patients with Parkinson’s disease (PD). We evaluated 88 healthy subjects and 101 patients with PD using a simplified motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr and Schwab and England scales, Geriatric Depression Scale, Pfeffer Functional Activities Questionnaire, Clinical Dementia Rating, Mini-Mental State Examination, clock drawing test, digit span, word list battery of the Consortium to Establish a Registry for Alzheimer’s Disease assessment, Frontal Assessment Battery, semantic verbal fluency test, and the ILFT. Diagnoses of mild cognitive impairment and dementia were made using the Movement Disorder Society diagnostic criteria. ILFT scores in healthy subjects correlated significantly with age (p = 0.001) and only one healthy subject scored 2 in the test. ILFT scores were significantly lower in patients with PD and dementia (p = 0.001) and significantly correlated with cognitive and functional tests, but not with depressive symptoms (p = 0.607), Hoehn and Yahr scores (p = 0.907), or Schwab and England scores (p = 0.701). Twenty-five patients with dementia, three patients with mild cognitive impairment, and six patients with apparently normal cognition scored less than 3 in the ILFT. The area under the receiver operating characteristic curve for the ILFT to discriminate patients with dementia from those without it was 0.76 (cut-off score of 3/2: sensitivity of 61%, specificity of 0.85). In conclusion, the ILFT seems to be a useful bedside test to assess cognitive impairment in patients with PD.     

Abnormal MoCA and normal range MMSE scores in Parkinson disease without dementia: Cognitive and neurochemical correlates

BackgroundThe Montreal Cognitive Assessment (MoCA) is increasingly being used as a cognitive screening test in Parkinson disease (PD). The MoCA's popularity likely reflects its ability to detect executive dysfunction, a relative deficiency of the Mini-Mental State Examination (MMSE).ObjectiveTo compare neurochemical and neuropsychological functions in non-demented PD patients with mild cognitive impairment (PD-MCI) and without, as defined by MoCA (PD-MCI = MoCA<26).MethodsNon-demented PD subjects underwent combined MoCA and MMSE, detailed cognitive testing and [¹¹C]methyl-4-piperidinyl propionate acetylcholinesterase and [¹¹C]dihydrotetrabenazine monoaminergic PET imaging.ResultsEighteen subjects met MoCA PD-MCI criteria but had MMSE scores in the normal range, compared to 29 subjects with normal MoCA and MMSE scores. The MoCA-defined PD-MCI group had reduced performance in global cognition (t = 2.91, P = 0.0056), most significantly in executive function (t = 3.18, P = 0.002), as well as significant reduction in dorsal caudate nucleus dopaminergic innervation (t = 2.72, P = 0.009) compared to the PD without MCI group. Both MoCA and MMSE had poor diagnostic accuracy for PD-MCI (65.3%) when using the Level 2 Movement Disorder Society Task Force definition.ConclusionPD subjects with normal range MMSE but abnormal MoCA scores had evidence of caudate nucleus dopaminergic denervation and mild cognitive changes, predominantly in executive function. The MoCA may be able to preferentially detect executive dysfunction compared to the MMSE, but the MoCA has limited diagnostic accuracy for PD-MCI, and should not be used alone to make this diagnosis.     

Cognitive decline and quality of life in incident Parkinson's disease: The role of attention

IntroductionParkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort.MethodsRecently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition.ResultsBaseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = −2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = −0.4, p < 0.01).ConclusionsPD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL.     

Parkinson's disease may worsen outcomes from coronavirus disease 2019 (COVID-19) pneumonia in hospitalized patients: A systematic review,meta-analysis,and meta-regression

BackgroundParkinson's Disease (PD) is among one of the common comorbidities in older patients. People with PD may be more vulnerable to severe pneumonia, due to the impairment of pulmonary function. Currently, the association between PD and COVID-19 is not yet established. This study aims to analyze the relationship between PD and in-hospital outcomes of COVID-19.Materials and methodsWe systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 25th, 2020. All articles published on COVID-19 and Parkinson's Disease were retrieved. The quality of the study was assessed using the Newcastle Ottawa Scale (NOS) tool for observational studies and Joanna Briggs Institute (JBI) Critical Appraisal Tools for cross-sectional studies. Statistical analysis was done using Review Manager 5.4 software.ResultsA total of 12 studies with 103,874 COVID-19 patients were included in this meta-analysis. This meta-analysis showed that Parkinson's Disease was associated with poor in-hospital outcomes [[OR 2.64 (95% CI 1.75–3.99), p < 0.00001, I² = 81%] and its subgroup which comprised of severe COVID-19 [OR 2.61 (95% CI 1.98–3.43), p < 0.00001, I² = 0%] and mortality from COVID-19 [RR 2.63 (95% CI 1.50–4.60), p = 0.0007, I² = 91%]. Meta-regression showed that the association was influenced by age (p = 0.05), but not by gender (p = 0.46) and dementia (p = 0.23).ConclusionsExtra care and close monitoring should be provided to Parkinson's Disease patients to minimize the risk of infections, preventing the development of severe and mortality outcomes.     

Homocysteine and cognitive function in Parkinson's disease

IntroductionIncreased plasma homocysteine (HC) is a risk factor for dementia in the general population. Levodopa therapy causes increased plasma HC, but it remains unclear whether elevated plasma HC is associated with cognitive impairment in Parkinson's disease (PD).MethodsThe study population includes all participants in the Pacific Northwest Udall Center (PANUC) Clinical cohort at the time of the study, consisting of 294 individuals with PD who had a standardized neuropsychological assessment and plasma collection for HC measurement. We tested the hypothesis that elevated plasma HC is inversely related to cognitive function in patients with PD.ResultsAs expected, plasma HC was positively associated with age, disease duration, disease severity, and levodopa usage, while cognitive function was associated with age, education, gender, and APOE genotype, so subsequent analyses controlled for these covariates. When plasma HC was dichotomized as normal (<14 μmol/L) or elevated (≥14 μmol/L), subjects with hyper-homocysteinemia had lower scores on Digit Symbol (p = 0.031), Hopkins Verbal Learning Task (HVLT) Delayed Recall (p = 0.004), and semantic verbal fluency (p = 0.049). When examined as a continuous variable, plasma HC was inversely associated with HVLT Delayed Recall (p = 0.009)) and semantic verbal fluency (p = 0.004), but was not significantly related to Digit symbol, Trail-making test, Judgment of Line Orientation, phonemic verbal fluency, MMSE, or MOCA. When analysis was restricted to non-demented subjects (n = 231), the findings were unchanged.ConclusionsWe conclude that plasma HC is significantly associated with some aspects of cognitive function in PD, and may represent a treatable risk factor for cognitive decline in PD.     

Cognitive impairment and sedentary behavior predict health-related attrition in a prospective longitudinal Parkinson's disease study

IntroductionIn Parkinson's disease (PD), the high burden of motor and non-motor symptoms, such as cognitive impairment or falls, is associated with rapid disease progression and mortality. This is often reflected by an increased drop-out rate of PD patients in longitudinal studies. Active physical behavior can impact the disease course beneficially and has an overall positive effect on health. Contrarily, sedentary behavior is associated with cognitive impairment in PD. The aim of this study was to investigate whether sedentary physical behavior assessed in the home environment and cognitive impairment can predict health-related study attrition due to sickness and death in PD.MethodsData of 45 PD patients, longitudinally assessed, were analyzed. Of those, 20 patients completed six yearly visits, 16 dropped out due to sickness or death, and nine for other reasons. All patients wore a mobile device to assess physical behavior and completed cognitive testing.ResultsLogistic regression revealed global cognition was the primary predictor for health-related drop-out in varying models (p ≤ .04). In the survival analysis, cognitive impairment (p = .005) and longer sedentary mean bout length (p = .02) were associated with drop-out due to sickness and death. The occurrence of health-related study drop-out or death was highest in patients with both impaired cognition and longer sedentary bouts.ConclusionsCognition was the primary predictor for study drop-out due to sickness and death. However, it seems that sedentary behavior might have a potential negative influence on PD patients’ health, especially those with cognitive impairment.