Relation between freezing of gait and frontal function in Parkinson's disease

IntroductionFreezing of gait (FOG) is a common symptom of Parkinson's disease (PD). Although the pathophysiological mechanism of FOG is unknown, previous studies have suggested that frontal dysfunction is associated with FOG. The Behavioral Assessment of the Dysexecutive Syndrome (BADS) battery, which is wide-ranging neurological battery composed of six subtests, evaluates frontal function and is more sensitive to executive dysfunction (ED) than other tools in PD patients. This is the first study to assess the relation between FOG in the ‘on’ state and frontal dysfunction evaluated using BADS.MethodsSubjects were 65 patients with PD. Multiple logistic regression analysis was used to compare the age-controlled standardized BADS score, age, disease duration, Hoehn and Yahr (HY) stage, levodopa-equivalent daily dose, and Mini-Mental State Examination (MMSE) score across patients with FOG (n = 43) and patients without FOG (n = 22). Score on each of the six BADS subtests were compared across patients with and without FOG using the Mann–Whitney U test.ResultsMultiple logistic regression analysis revealed that FOG was related to lower age-controlled standardized BADS score (P = 0.022) and higher HY stage (P = 0.009) but not to disease duration, levodopa equivalent daily dose, or MMSE score. Among the six BADS subtests, score on the Zoo Map Test, which evaluates problem solving and planning, was lower in patients with FOG than in patients without FOG.ConclusionThese results support a relation between on-state FOG and frontal dysfunction in PD patients.     

Thalamic volume and related visual recognition are associated with freezing of gait in non-demented patients with Parkinson's disease

BackgroundThe pathophysiology of freezing of gait (FOG) in non-demented Parkinson's disease (PD) patients remains poorly understood. Recent studies have suggested that neurochemical alterations in the cholinergic systems play a role in the development of FOG. Here, we evaluated the association between subcortical cholinergic structures and FOG in patients with non-demented PD.MethodsWe recruited 46 non-demented patients with PD, categorized into PD with (n = 16) and without FOG (n = 30) groups. We performed neuropsychological test, region-of-interest-based volumetric analysis of the substantia innominata (SI) and automatic analysis of subcortical brain structures using a computerized segmentation procedure.ResultsThe comprehensive neuropsychological assessment showed that PD patients with FOG had lower cognitive performance in the frontal executive and visual-related functions compared with those without freezing of gait. The normalized SI volume did not differ significantly between the two groups (1.65 ± 0.18 vs. 1.68 ± 0.31). The automatic analysis of subcortical structures revealed that the thalamic volumes were significantly reduced in PD patients with FOG compared with those without FOG after adjusting for age, sex, disease duration, the Unified PD Rating Scale scores and total intracranial volume (left: 6.71 vs. 7.16 cm³, p = 0.029, right: 6.47 vs. 6.91 cm³, p = 0.026). Multiple linear regression analysis revealed that thalamic volume showed significant positive correlations with visual recognition memory (left: β = 0.441, p = 0.037, right: β = 0.498, p = 0.04).ConclusionsThese data suggest that thalamic volume and related visual recognition, rather than the cortical cholinergic system arising from the SI, may be a major contributor to the development of freezing of gait in non-demented patients with PD.     

Dorsal rather than ventral visual pathways discriminate freezing status in Parkinson's disease

BackgroundAlthough visuospatial deficits have been linked with freezing of gait (FOG) in Parkinson's disease (PD), the specific effects of dorsal and ventral visual pathway dysfunction on FOG is not well understood.MethodWe assessed visuospatial function in FOG using an angle discrimination test (dorsal visual pathway bias) and overlapping figure test (ventral visual pathway bias), and recorded overall response time, mean fixation duration and dwell time. Covariate analysis was conducted controlling for disease duration, motor severity, contrast sensitivity and attention with Bonferroni adjustments for multiple comparisons.ResultsTwenty seven people with FOG, 27 people without FOG and 24 controls were assessed. Average fixation duration during angle discrimination distinguished freezing status: [F (1, 43) = 4.77 p < 0.05] (1-way ANCOVA).ConclusionResults indicate a preferential dysfunction of dorsal occipito-parietal pathways in FOG, independent of disease severity, attentional deficit, and contrast sensitivity.     

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.     

Thalamic volume mediates associations between cardiorespiratory fitness (VO2max) and cognition in Parkinson's disease

IntroductionCognitive deficits occur in Parkinson's disease (PD). Cardiorespiratory fitness (CRF) is associated with better cognitive performance in aging especially in executive function (EF) and memory. The association between CRF and cognitive performance is understudied in people with PD. Brain structures underlying associations also remains unknown. This cross-sectional study examined the associations between CRF and cognitive performance in PD. We also examined associations between CRF and brain structures impacted in PD. Mediation analysis were conducted to examine whether brain structures impacted in PD mediate putative associations between CRF and cognitive performance.MethodsIndividuals with PD (N = 33) underwent magnetic resonance imaging (MRI), CRF evaluation (estimated VO₂max), and neuropsychological assessment. Composite cognitive scores of episodic memory, EF, attention, language, and visuospatial functioning were generated. Structural equation models were constructed to examine whether MRI volume estimates (thalamus and pallidum) mediated associations between CRF and cognitive performance (adjusting for age, education, PD disease duration, sex, MDS-UPDRS motor score, and total intracranial volume).ResultsHigher CRF was associated with better episodic memory (Standardized β = 0.391; p = 0.008), EF (Standardized β = 0.324; p = 0.025), and visuospatial performance (Standardized β = 0.570; p = 0.005). Higher CRF was associated with larger thalamic (Standardized β = 0.722; p = 0.004) and pallidum (Standardized β = 0.635; p = 0.004) volumes. Thalamic volume mediated the association between higher CRF and better EF (Indirect effect = 0.309) and episodic memory (Indirect effect = 0.209) performance (p < 0.05). The pallidum did not significantly mediate associations between CRF and cognitive outcomes.ConclusionThe thalamus plays an important role in the association between CRF and both EF and episodic memory in PD.     

Visual complaints and visual hallucinations in Parkinson's disease

BackgroundVisual symptoms are common in Parkinson's disease (PD) and are frequently under-diagnosed. The detection of visual symptoms is important for differential diagnosis and patient management.AimTo establish the prevalence of recurrent visual complaints (RVC) and recurrent visual hallucinations (RVH) and to investigate their interaction in PD patients and controls.MethodsThis cross-sectional study included 88 PD patients and 90 controls. RVC and RVH were assessed with a visual symptom questionnaire and the North-East-Visual-Hallucinations-Interview (NEVHI).ResultsDouble vision (PD vs. Controls: 18.2% vs. 1.3%; p < 0.001), misjudging objects when walking (PD vs. Controls: 12.5% vs. 1.3%; p < 0.01), words moving whilst reading (PD vs. Controls: 17.0% vs. 1.3%; p < 0.001) and freezing in narrow spaces (PD vs. Controls: 30.7% vs. 0%; p < 0.001) were almost exclusively found in PD patients. The same was true for recurrent complex visual hallucinations and illusions (PD vs. Controls: both 17.0% vs. 0%; p < 0.001). Multiple RVC (43.2% vs. 15.8%) and multiple RVH (29.5% vs. 5.6%) were also more common in PD patients (both p < 0.001). RVC did not predict recurrent complex visual hallucinations; but double vision (p = 0.018, R² = 0.302) and misjudging objects (p = 0.002, R² = 0.302) predicted passage hallucinations. Misjudging objects also predicted the feeling of presence (p = 0.010, R² = 0.321).ConclusionsMultiple and recurrent visual symptoms are common in PD. RVC emerged as risk factors predictive of the minor forms of hallucinations, but not recurrent complex visual hallucinations.     

Sex differences in cerebral energy metabolism in Parkinson's disease: A phosphorus magnetic resonance spectroscopic imaging study

ObjectiveTo test the hypothesis that there are sex differences in cerebral energy metabolism in Parkinson's disease (PD).MethodsPhosphorus magnetic resonance spectroscopy (³¹P MRS) was used to determine high-energy phosphate (phosphocreatine and ATP) and low-energy phosphate (free phosphate) levels in the striatum and temporoparietal cortical gray matter (GM) in 10 men and 10 women with PD, matched for age at onset, disease duration, and UPDRS scores.ResultsIn the hemisphere more affected by PD, both ATP and high energy phosphate (HEP: phosphocreatine + ATP) content in striatum was 15% lower in men versus women with PD (p = .050 and p = .048, respectively). Similar decreases by 16% in ATP (p = .023) and 12% in HEP (p = .046) were observed in GM in men versus women with PD. In contrast, there were no detectable sex differences in ATP or HEP in healthy age-matched controls.ConclusionsMen with PD have lower levels of ATP and high energy phosphate than women in brain regions affected by PD. These findings suggest that there may be a greater burden of mitochondrial dysfunction in PD in men versus women with PD.     

Motor,behavioural, and cognitive correlates of fatigue in early,de novo Parkinson disease patients

IntroductionFatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.MethodsEighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.ResultsTwelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), “episodic anxiety” subscale of PAS (p = 0.005), and “cognitive apathy” subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745).ConclusionIn a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.     

Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease

BackgroundHallucinations are a frequent and severe complication in Parkinson's disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD.In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM).MethodsWe prospectively collected a sample of 46 non-demented PD patients, with (N = 17) and without (n = 29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function. Presence and type of minor psychotic phenomena was assessed by the new MDS-UPDRS. Three dimensional T1-weighted MRI images were acquired with a 1.5 T magnet, and analyzed using optimized VBM.ResultsCompared to controls, PD with minor hallucinations (PD-mH) showed reduced gray matter volume bilaterally in different areas of the dorsal visual stream, and in functionally related midbrain and cerebellar structures. Additionally, bilateral gray matter volume increases were observed in the PD-mH group in limbic and paralimbic regions.ConclusionsOur data support a major role of the dorsal visual stream in the genesis of minor hallucinations in PD, reinforcing the importance of posterior cortical regions for the development of cognitive and psychiatric complications in PD.     

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.     

Impaired contrast sensitivity is associated with more severe cognitive impairment in Parkinson disease

ObjectivesDopaminergic degeneration affects both nigrostriatal projection neurons and retinal amacrine cells in Parkinson disease (PD). Parkinsonian retinopathy is associated with impaired color discrimination and contrast sensitivity. Some prior studies described associations between color discrimination deficits and cognitive deficits in PD, suggesting that contrast discrimination deficits are due, at least in part, to cognitive deficits in PD. We investigated the relationship between cognitive deficits and impaired contrast sensitivity in PD.MethodsPD subjects, n = 43; 15F/28M; mean age 66.5 ± 8.2, Hoehn and Yahr stage 2.6 ± 0.6, and duration of disease of 6.2 ± 5.0 years underwent neuropsychological and Rabin contrast sensitivity testing.ResultsMean Rabin contrast sensitivity score was 1.34 ± 0.40. Bivariate analyses showed significant correlation between Rabin contrast sensitivity scores and global cognitive z-scores (R = 0.54, P = 0.0002). Cognitive domain Z-score post hoc analysis demonstrated most robust correlation between Rabin scores and executive functions (R = 0.49, P = 0.0009), followed by verbal learning (R = 0.44, P = 0.0028), visuospatial (R = 0.39, P = 0.001) and attention z-scores (R = 0.32, P = 0.036).ConclusionsImpaired contrast sensitivity in PD is robustly associated with cognitive deficits, particularly executive function deficits. These results suggest that contrast sensitivity may be a useful biomarker for cognitive changes in PD and may have implications for driving safety evaluations in PD.     

Hyposmia and cardiovascular dysautonomia correlatively appear in early-stage Parkinson's disease

ObjectiveOlfactory dysfunction is considered to precede motor symptoms and early markers of Parkinson's disease (PD), while the relative time at which cardiovascular dysautonomia appears in PD is not well understood. To assess the appearance of cardiovascular dysautonomia in PD, we evaluated its relation to olfactory dysfunction in early-stage PD patients.MethodsTwenty-three non-demented PD patients within 2 years from the onset of motor symptoms were enrolled. We evaluated olfactory dysfunction by the Odor Stick Identification Test for Japanese (OSIT-J) and analyzed its relationship to the results of other cardiovascular autonomic tests and cardiac ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy.ResultsThere was a correlation between olfactory scores and increased blood pressure in both the norepinephrine (r = 0.75, p < 0.0001, n = 21) and dobutamine (r = 0.57, p = 0.0087, n = 20) infusion tests and cardiac MIBG uptake (r = 0.42, p = 0.049, n = 23). The fall in orthostatic blood pressure during the head-up tilt test was not correlated with the olfactory scores, but the Valsalva maneuver revealed that OSIT-J scores correlated with the pressure recovery time from phase III to the return of blood pressure to baseline (r = 0.54, p = 0.037, n = 15) and with the magnitude of blood pressure overshoot during phase IV (r = 0.67, p = 0.0016, n = 20).ConclusionOur results demonstrate that extensive components of the cardiovascular sympathetic system as well as the olfactory system are correlatively impaired in the early stage of PD, suggesting that degeneration of broad aspects of the cardiovascular sympathetic system occurs concurrently with olfactory system degeneration during the premotor phase of PD.     

Apolipoprotein E ε4 genotype and risk of freezing of gait in Parkinson's disease

ObjectiveTo investigate the association between Apolipoprotein E (APOE) genotype and freezing of gait (FOG) in Parkinson's disease (PD).MethodsThis cohort study included 339 early PD patients who were divided into APOE ε4-positive (n = 88) and ε4-negative (n = 251) groups. They were followed-up for up to 6 years to identify the development of FOG. To investigate the influence of CSF β-amyloid 1–42 (Aβ₄₂) on the association between APOE ε4 and FOG, the patients were additionally dichotomized into “high-level” and “low-level” groups using three different cutoff values for the CSF Aβ₄₂ levels.ResultsAt baseline, the APOE ε4-positive group had lower CSF Aβ₄₂ levels than the APOE ε4-negative group. During a median follow-up of 5.0 years, the APOE ε4-positive group had a higher incidence of FOG than the APOE ε4-negative group. In the multivariable Cox model excluding CSF Aβ₄₂, APOE ε4 was a significant predictor of FOG. However, after adding CSF Aβ₄₂ in the model, APOE ε4 did not survive, whereas lower CSF Aβ₄₂ levels were associated with FOG. In the subgroup analyses, the effect of the APOE ε4 allele was not found in the “low-level” group. However, in the “high-level” group, the APOE ε4 allele independently increased the risk of FOG, and this association was stronger than the association with CSF Aβ₄₂.ConclusionThe APOE ε4 allele may be a novel genetic risk factor for FOG in PD. This association seemed to be mainly mediated by Aβ-dependent pathways, but its Aβ-independent effects might also contribute to the development of FOG.     

Depression may negatively affect the change in freezing of gait following subthalamic nucleus stimulation in Parkinson's disease

ObjectiveTo assess the influence of preoperative depression on the change in freezing of gait (FOG) following subthalamic nucleus stimulation (STN-DBS) in patients with Parkinson's disease (PD).MethodsOne hundred and twelve PD patients were included who received bilateral STN-DBS. Of these, 33 had no preoperative depression (PD-ND) and the other 79 had preoperative depression (PD-D). Each PD-ND patient was matched with one PD-D patient by the propensity score for which sex, age at PD onset, disease duration, UPDRS-III score during off-medication state, levodopa-equivalent daily dose, and mini mental state examination were the independent variables. We compared both a FOG-questionnaire (FOG-Q) and the axial score from UPDRS-III between the two groups over 12-month follow-up.ResultsDuring the off-medication state, FOG-Q at 12-month was decreased with STN-DBS in both PD-ND (−52.9%, p < 0.001) and PD-D (−24.2%, p < 0.001) with a significant difference in the change of FOG in favor of PD-ND (p = 0.001). Similarly, there was an improvement in the axial score for both PD-ND (−66.1%, p < 0.001) and PD-D (−45.3%, p < 0.001) at 12-month with a significant difference between the groups. (p = 0.005). During the on-medication state, both the FOG-Q and axial score at 12-month were not improved with STN-DBS in the PD-ND and PD-D with no difference between the groups.ConclusionsOur findings suggest that preoperative depression negatively affects the outcome of FOG following STN-DBS in the off-medication state but not in the on-medication state.     

Cognitive correlates of visual hallucinations in non-demented Parkinson's disease patients

BackgroundVisual hallucinations (VH) in Parkinson's disease (PD) are associated with PD dementia and have been related to cognitive impairments in non-demented PD patients. Reports on the specific cognitive domains affected are conflicting. The aim of the present study was to investigate the presence of specific cognitive impairments in non-demented PD patients with VH, compared to those without VH.MethodsWe compared the clinical characteristics and neuropsychological test scores of 31 non-demented PD patients with VH with those of 31 PD patients without VH that were carefully matched for sex, age, disease duration and educational level. Several non-motor symptoms, including depression, anxiety and sleep disturbances, were also taken into account, as these may influence cognitive performance.ResultsThe PD with VH group performed significantly worse on the Trail Making Test part A (p = 0.01) and the Rey Auditory Verbal Learning Test, immediate recall (p = 0.01). In addition, PD patients with VH were more anxious, more depressed and reported more sleep disturbances. Verbal learning scores were not associated with levels of anxiety, depression or sleep disruption, whereas worse Trail Making Test A performance was associated with concomitant sleep disturbances.ConclusionsIn non-demented PD patients, the presence of VH is associated with a cognitive profile characterized by impairments in verbal learning and probably attention. Since these cognitive functions are believed to be non-dopaminergic mediated functions, the present results support the hypothesis that multiple neurotransmitter systems, other than dopamine, contribute to the pathophysiology of VH in PD.     

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.     

Forehead sympathetic skin responses in determining autonomic involvement in Parkinson’s disease

ObjectiveThe purpose of this study was to evaluate forehead sympathetic skin response (SSR) and demonstrate any differences with extremity SSR in determining autonomic nervous system (ANS) involvement in patients with Parkinson’s disease (PD).MethodsTwenty early stage, 20 advanced stage idiopathic PD patients and 20 healthy controls participated in this study. SSR of forehead, hands and feet, heart rate variability (HRV), orthostatic intolerance, QT intervals and dysautonomic symptoms were evaluated.ResultsAbsent forehead SSR was determined unilaterally in 4, bilaterally in 7 early stage patients, and unilaterally in 4, bilaterally in 8 advanced stage PD patients; there was significant difference between early and advanced stage PD and control groups in terms of the lack of SSR (p = 0.000). Absent extremity SSR was determined in at least 1 extremity of 3 advanced stage PD patients, and none of the early stage PD patients. No difference was noted in HRV at rest between early and advanced stage PD and control groups (p = 0.218); but HRV at deep breathing was lower in both early and advanced PD patients compared to controls (p = 0.014, p = 0.002, respectively).ConclusionForehead SSR is more sensitive in determining ANS dysfunction not only in late but also in early stage of PD.SignificanceWith further supportive research, forehead SSR might be used as a simple diagnostic electrophysiological test in the early diagnosis of ANS dysfunction enabling proper treatment and increasing the quality of life of PD patients.     

The effects of gait impairment with and without freezing of gait in Parkinson's disease

ObjectiveTo compare the effects of gait impairment without freezing of gait (FOG) versus FOG without gait impairment in Parkinson’s disease (PD) on disability and quality of life.BackgroundFOG is frequently characterized as the major cause of gait-related disability in PD. However, gait impairment may also result from other PD symptoms including slowing, motor asymmetry, gait variability, dystonia or stooped posture.MethodsThe Unified Parkinson’s Disease Rating Scale (UPDRS), Older Americans Resources and Services Disability Scale (OARS) and the SF-12 Health Status Survey were used to evaluate patients with PD. Responses to UPDRS Items #14 (Freezing) and # 29 (Gait) were used to create 4 subgroups: 1) No FOG or gait impairment, 2) FOG, no gait impairment, 3) Gait impairment, no FOG, and 4) Both FOG and gait impairment. Disease severity, disability, and quality of life were compared across the subgroups with ANOVAs, and between subgroups with t-tests.Results916 PD patients were divided into 4 subgroups based on their gait and freezing score (#1: n = 213, #2: n = 41, #3: n = 323 and #4: n = 339). Total UPDRS progressively increased from Group 1 through Group 4 (1 = 25.2, 2 = 33.7, 3 = 39.2, 4 = 59.2; p < 0.001). Motor UPDRS also progressively increased (1 = 17.4, 2 = 19.7, 3 = 26.9, 4 = 36.5; p < 0.0001). Similarly, disability and health-related quality of life progressively increased from Group 1 through Group 4 (Total OARS: 1 = 15.3, 2 = 17.2, 3 = 18.9, 4 = 28.4; p < 0.001). Group 3 (Gait impairment, no FOG) showed greater disease severity than Group 2 (FOG, no gait impairment; Total and Motor UPDRS; p < 0.05), but the difference did not reach significance for disability or quality of life.ConclusionsGait impairment without FOG was associated with greater disease severity than FOG without gait impairment. The combination of gait impairment and FOG was associated with the greatest disease severity and disability. These results show differential effects of diverse features of gait impairment in PD and demonstrate the importance of gait features unrelated to freezing.     

Parkinson’s disease and REM sleep behavior disorder result in increased non-motor symptoms

ObjectiveRapid eye movement (REM)-sleep behavior disorder (RBD) is often comorbid with Parkinson’s disease (PD). The current study aimed to provide a detailed understanding of the impact of having RBD on multiple non-motor symptoms (NMS) in patients with PD.MethodsA total of 86 participants were evaluated for RBD and assessed for multiple NMS of PD. Principal component analysis was utilized to model multiple measures of NMS in PD, and a multivariate analysis of variance was used to assess the relationship between RBD and the multiple NMS measures. Seven NMS measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall NMS of PD.ResultsAmong the PD patients, 36 were classified as having RBD (objective polysomnography and subjective findings), 26 as not having RBD (neither objective nor subjective findings), and 24 as probably having RBD (either subjective or objective findings). RBD was a significant predictor of increased NMS in PD while controlling for dopaminergic therapy and age (p = 0.01). The RBD group reported more NMS of depression (p = 0.012), fatigue (p = 0.036), overall sleep (p = 0.018), and overall NMS (p = 0.002).ConclusionIn PD, RBD is associated with more NMS, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with RBD represent a subtype of PD with different disease progression and phenomenological presentation.     

Visuospatial functioning is associated with sleep disturbance and hallucinations in nondemented patients with Parkinson’s disease

Introduction: Cognitive impairment is a common symptom of Parkinson’s disease (PD) associated with reduced quality of life and a more severe disease state. Previous research has shown an association between visuospatial dysfunction and worse disease course; however, it is not clear whether this is separable from executive dysfunction and/or dementia. This study sought to determine whether distinct cognitive factors could be measured in a large PD cohort, and if those factors were differentially associated with other PD-related features, specifically to provide insight into visuospatial dysfunction.

Methods: Non-demented participants with PD from the Pacific Udall Center were enrolled (n = 197). Co-participants (n = 104) completed questionnaires when available. Principal components factor analysis (PCFA) was utilized to group the neuropsychological test scores into independent factors by considering those with big factor loading (≥.40). Linear and logistic regression analyses were performed to examine the relationship between the cognitive factors identified in the PCFA and other clinical features of PD.

Results: Six factors were extracted from the PCFA: 1) executive/processing speed, 2) visual learning & memory/visuospatial, 3) auditory working memory, 4) contextual verbal memory, 5) semantic learning & memory, and 6) visuospatial. Motor severity (p = 0.001), mood (p < 0.001), and performance on activities of daily living scores (informant: p < 0.001, patient: p = 0.009) were primarily associated with frontal and executive factors. General sleep disturbance (p < 0.006) and hallucinations (p = 0.002) were primarily associated with visuospatial functioning and visual learning/memory.

Conclusions: Motor symptoms, mood, and performance on activities of daily living were primarily associated with frontal/executive factors. Sleep disturbance and hallucinations were associated with visuospatial functioning and visual learning/memory only, over and above executive functioning and regardless of cognitive disease severity. These findings support that visuospatial function in PD may indicate a more severe disease course, and that symptom management should be guided accordingly.