Extended Timed Up and Go assessment as a clinical indicator of cognitive state in Parkinson\u27s disease

Objective: To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson’s disease (PD) severity and cognitive impairment. Methods: Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7 metres, turn 180 degrees and then return to the start, in a seated position. The extended-TUG assessment duration was correlated to a panel of clinical assessments, including the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Quality of Life (PDQ-39), Scales for Outcomes in Parkinson’s disease (SCOPA-Cog), revised Addenbrooke’s Cognitive Index (ACE-R) and Barratt’s Impulsivity Scale 11 (BIS-11). Results: Extended-TUG time was significantly correlated to MDS-UPDRS III score and to SCOPA-Cog, ACE-R (p\u3c0.001) and PDQ-39 scores (p\u3c0.01). Generalized linear models determined the extended-TUG to be a sole variable in predicting ACE-R or SCOPA-Cog scores. Patients in the fastest extended-TUG tertile were predicted to perform 8.3 and 13.4 points better in the SCOPA-Cog and ACE-R assessments, respectively, than the slowest group. Patients who exceeded the dementia cut-off scores with these instruments exhibited significantly longer extended-TUG times. Conclusions: Extended-TUG performance appears to be a useful indicator of cognition as well as motor function and quality of life in PD, and warrants further evaluation as a first line assessment tool to monitor disease severity and response to treatment. Poor extended-TUG performance may identify patients without overt cognitive impairment form whom cognitive assessment is needed

Author response: Effects of orthostatic hypotension on cognition in Parkinson disease

OBJECTIVE: To investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in persons with Parkinson's disease (PD) without dementia. METHODS: There were 55 participants: 37 non-demented individuals with idiopathic PD, including 18 with OH (PDOH), and 19 without (PDWOH), and18 control participants (C). All participants completed neuropsychological tests in the supine and in the upright tilted position. Blood pressure was assessed in each posture using a standardized oscillometric cuff at the right brachial artery. RESULTS: The two PD groups performed similarly while supine, with a profile notable for executive dysfunction consisting of deficits in sustained attention, response inhibition, and semantic verbal fluency, as well as reduced verbal memory encoding and retention. When upright, these deficits were exacerbated and broadened to include additional cognitive functions in the PDOH group: deficits in phonemic verbal fluency, psychomotor speed, and both basic and complex aspects of auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, though the PDOH group had a wider range of deficits in the executive functioning and memory domains and was the only group to show significant changes in visuospatial skills. CONCLUSIONS: Cognitive deficits in idiopathic PD have been widely reported, though assessments are typically performed in the supine position. While both PD groups had supine deficits that aligned with prior studies and clinical findings, we demonstrated that those with PD and orthostatic hypotension had transient, posture-mediated changes in excess of those found in PD without autonomic failure. These observed changes suggest an acute, reversible effect, and as orthostatic hypotension is a significant comorbid factor in PD, an independent target for clinical intervention. Further understanding of the effects of autonomic failure on cognition in other disorders is desirable, particularly in the context of neuroimaging studies and clinical assessments where data are collected only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with autonomic failure also has implications for functional activities of daily living and overall quality of life.Accepted manuscrip

A study on Cognitive Profile in Idiopathic Parkinson’s Disease

INTRODUCTION: Parkinson‟s disease (PD) is a degenerative disease named after James Parkinson (1755-1824) who described this condition in his publication in 1817 called „Essay on Shaking Palsy. Among the neurodegenerative diseases it ranks second after Alzheimer‟s disease (AD). It is more common in the elderly, although early onset disease is well known. It has characteristic clinical features of bradykinesia and at least one the following: muscular rigidity, 4-6Hz. rest tremor and postural instability. Diagnosis is usually made by the well validated criteria called “UKPDS” (UK Parkinson‟s Disease Society Brain Bank criteria). Apart from motor manifestations there are number of non-motor manifestations which is a common source of disability in PD. AIM OF THE STUDY: 1. To identify the range of cognitive impairment if any inpatients with Idiopathic Parkinson‟s disease. 2. To identify subclinical cognitive impairment in newly diagnosed idiopathic Parkinson‟s disease. MATERIALS AND METHODS: 100 patients with Idiopathic Parkinson‟s disease who attended Neurological services at Rajiv Gandhi Govt. General hospital, Chennai were included for the study. Study Design: Single centre, non- randomized prospective study. Study Period: Study was conducted between September 2012 and January 2014. Ethical committee approval was obtained. Inclusion Criteria: Newly diagnosed patients with Idiopathic Parkinson‟s disease aged between 55and 75 years and not started on anti parkinsonian drugs were included for the study. Exclusion Criteria: 1. Very ill patients (moribund state), 2. Presence of depression (pseudodementia), behavior disorders or delirium, 3. Symptomatic parkinsonism dementia complex [vascular, tumor, NPH], 4. Coincident degenerative dementia like AD. 5. Degenerative diseases presenting with Parkinsonism and dementia namely Progressive supranuclear palsy (PSP), Cortico basal degeneration (CBD) and Dementia in Lewy body disease (DLB). 6. Vascular risk factors like Diabetes mellitus, Hypertension and also history of stroke RESULTS: The total number of patients included in the study was 100. The parameters analysed were Age, Duration of illness, Educational status, Hoehn and Yahr stage, and UPDRS score. Each of these parameters was compared with the individual cognitive scalenamely MMSE, ACE-R scale, MoCA and FAB test. Other non- motor manifestations quoted in the review of literature like behavioural disturbances, psychosis, mood disorders, sleep disorders, autonomic disturbances, sensory disturbances and sensation of smell are beyond the scope of this study, and therefore were not analyzed. CONCLUSION: 1. Patients with Parkinson‟s disease were found to have cognitive impairment on formal neuropsychological testing, though they do not show functional restriction in activities of daily living. 2. There is clear linear relationship between age of patients and duration of illness in developing cognitive impairment. 3. Mild cognitive impairment is seen in early stages of Parkinson‟s disease. This is observed even in patients with low score for UPDRS and Hoehn and Yahr scales. This trend is reflected across all domains of cognitive testing used. This is particularly so with the frontal lobe functions and less so with testing for fluency and language. 4. Frank dementia however, was found only in proportion of patients especially those with more advanced disease. 5. This study highlights the importance of screening of cognition in patients with Parkinson‟s disease. If cognitive impairment is found, it will help to intervene in the early stages of the illness

Cognitive training interventions for dementia and mild cognitive impairment in Parkinson's disease

Background Approximately 60% to 80% of people with Parkinson's disease (PD) experience cognitive impairment that impacts on their quality of life. Cognitive decline is a core feature of the disease and can often present before the onset of motor symptoms. Cognitive training may be a useful non‐pharmacological intervention that could help to maintain or improve cognition and quality of life for people with PD dementia (PDD) or PD‐related mild cognitive impairment (PD‐MCI). Objectives To determine whether cognitive training (targeting single or multiple domains) improves cognition in people with PDD and PD‐MCI or other clearly defined forms of cognitive impairment in people with PD. Search methods We searched the Cochrane Dementia and Cognitive Improvement Group Trials Register (8 August 2019), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and PsycINFO. We searched reference lists and trial registers, searched relevant reviews in the area and conference proceedings. We also contacted experts for clarifications on data and ongoing trials. Selection criteria We included randomised controlled trials where the participants had PDD or PD‐MCI, and where the intervention was intended to train general or specific areas of cognitive function, targeting either a single domain or multiple domains of cognition, and was compared to a control condition. Multicomponent interventions that also included motor or other elements were considered eligible. Data collection and analysis Two review authors independently screened titles, abstracts, and full‐text articles for inclusion in the review. Two review authors also independently undertook extraction of data and assessment of methodological quality. We used GRADE methods to assess the overall quality of the evidence. Main results Seven studies with a total of 225 participants met the inclusion criteria for this review. All seven studies compared the effects of a cognitive training intervention to a control intervention at the end of treatment periods lasting four to eight weeks. Six studies included people with PD living in the community. These six studies recruited people with single‐domain (executive) or multiple‐domain mild cognitive impairment in PD. Four of these studies identified participants with MCI using established diagnostic criteria, and two included both people with PD‐MCI and people with PD who were not cognitively impaired. One study recruited people with a diagnosis of PD dementia who were living in long‐term care settings. The cognitive training intervention in three studies targeted a single cognitive domain, whilst in four studies multiple domains of cognitive function were targeted. The comparison groups either received no intervention or took part in recreational activities (sports, music, arts), speech or language exercises, computerised motor therapy, or motor rehabilitation combined with recreational activity. We found no clear evidence that cognitive training improved global cognition. Although cognitive training was associated with higher scores on global cognition at the end of treatment, the result was imprecise and not statistically significant (6 trials, 178 participants, standardised mean difference (SMD) 0.28, 95% confidence interval (CI) −0.03 to 0.59; low‐certainty evidence). There was no evidence of a difference at the end of treatment between cognitive training and control interventions on executive function (5 trials, 112 participants; SMD 0.10, 95% CI −0.28 to 0.48; low‐certainty evidence) or visual processing (3 trials, 64 participants; SMD 0.30, 95% CI −0.21 to 0.81; low‐certainty evidence). The evidence favoured the cognitive training group on attention (5 trials, 160 participants; SMD 0.36, 95% CI 0.03 to 0.68; low‐certainty evidence) and verbal memory (5 trials, 160 participants; SMD 0.37, 95% CI 0.04 to 0.69; low‐certainty evidence), but these effects were less certain in sensitivity analyses that excluded a study in which only a minority of the sample were cognitively impaired. There was no evidence of differences between treatment and control groups in activities of daily living (3 trials, 67 participants; SMD 0.03, 95% CI −0.47 to 0.53; low‐certainty evidence) or quality of life (5 trials, 147 participants; SMD −0.01, 95% CI −0.35 to 0.33; low‐certainty evidence). There was very little information on adverse events. We considered the certainty of the evidence for all outcomes to be low due to risk of bias in the included studies and imprecision of the results. We identified six ongoing trials recruiting participants with PD‐MCI, but no ongoing trials of cognitive training for people with PDD. Authors' conclusions This review found no evidence that people with PD‐MCI or PDD who receive cognitive training for four to eight weeks experience any important cognitive improvements at the end of training. However, this conclusion was based on a small number of studies with few participants, limitations of study design and execution, and imprecise results. There is a need for more robust, adequately powered studies of cognitive training before conclusions can be drawn about the effectiveness of cognitive training for people with PDD and PD‐MCI. Studies should use formal criteria to diagnose cognitive impairments, and there is a particular need for more studies testing the efficacy of cognitive training in people with PDD

Categorising Visual Hallucinations in Early Parkinson's Disease.

BACKGROUND: Visual hallucinations (VHs) are common in Parkinson's disease (PD), with prevalence ranging from 27-50% in cross-sectional cohorts of patients with well-established disease. However, minor hallucinations may occur earlier in the disease process than has been previously reported. OBJECTIVE: We sought to categorise VHs in a cohort of newly diagnosed PD patients and establish their relationship to other clinical features. METHODS: Newly diagnosed PD participants (n = 154) were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in PD (ICICLE-PD) study. Participants completed the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS III), Montreal Cognitive Assessment (MoCA) and Parkinson's Disease Questionnaire (PDQ-39) to assess motor severity, cognition and quality of life (QoL), respectively. VHs were classified using the North East Visual Hallucinations Inventory. Hierarchical regression was used to build predictive models of motor severity, QoL and cognition. RESULTS: 22% (n = 34) of participants experienced recurrent VHs with minor VHs being most frequently reported (64.7% of hallucinators). Complex VHs were present in 32.4% of hallucinating participants. Linear regression showed VHs predicted poorer PDQ-39 and MoCA scores (β= 0.201, p = 0.006 and β= - 0.167, p = 0.01, respectively) but not motor severity (p > 0.05). CONCLUSIONS: Over a fifth of people with newly diagnosed PD reported recurrent VHs; minor hallucinations were the most common, although a small proportion reported complex VHs. Recurrent VHs were found to be a significant independent predictor of cognitive function and QoL but not motor severity. Our findings highlight the importance of screening for VHs at diagnosis.ICICLE-PD was funded by Parkinson’s UK (J-0802, G-1301, G-1507). The research was supported by the Lockhart Parkinson’s Disease Research Fund, the National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University and a NIHR Biomedical Research Centre award to the University of Cambridge/Addenbrooke’s Hospital

Inflammation in Mild Cognitive Impairment due to Parkinson’s disease, Lewy Body disease and Alzheimer’s disease

Background Abstract Inflammation appears to play a role in the progression of neurodegenerative diseases. However, little is known about inflammation during early stages of cognitive decline or whether this differs in different disease groups. We sought to investigate this by assessing the inflammatory profile in patients with Parkinson’s disease with the early stages of cognitive impairment (PD-MCI), patients with prodromal Alzheimer’s disease (MCI-AD), prodromal Lewy Body disease (MCI-LB) and controls. Methods We obtained venous blood samples from participants with PD-MCI (n = 44), PD-normal cognition (n = 112) MCI-LB (n = 38), MCI-AD (n = 21) and controls (n = 84). We measured 10 cytokines using Meso Scale Discovery V-Plex Plus including interferon-gamma, interleukin (IL)-10, IL-12p70, IL-13, IL-1beta, IL- 2, IL-4, IL-6, IL-8 and tumour necrosis factor alpha. High-sensitivity C–reactive protein was measured. Results There was a higher level of inflammation in patients with MCI-AD and MCI-LB compared with controls. PD non-cognitively impaired had higher inflammatory markers than controls but there was no difference between PD-MCI and controls. There was a decrease in inflammatory markers with increasing motor severity based on the Unified Parkinson’s Disease Rating Scale. Conclusions Inflammation may be involved in the onset of cognitive decline in patients with MCI-AD and MCI-LB but appears to be less prominent PD-MCI albeit in a small data set. This suggests that anti- inflammatory medications may have most benefit at the earliest stages of neurodegenerative diseases. For PD cases, this might be in advance of the development of MCI.The LewyPro work was funded by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre in Lewy Body Dementia based at Newcastle upon Tyne NHS Foundation Trust and Newcastle University and The Royal College of Psychiatrists Pathfinder Fellowship. ICICLE-PD was funded by Parkinson’s UK (J-0802, G-1507). The research was supported by the Lockhart Parkinson’s Disease Research Fund, the academy of Medical Sciences UK, the Rosetrees Trust, and the Stevenage Biosciences Catalyst, the National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit based at Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University and the NIHR Cambridge Biomedical Research Centre. CWG is supported by a Clinician Scientist Fellowship from the MRC

The relation of anxiety and cognition in Parkinson's disease

OBJECTIVE: Parkinson’s disease (PD) has long been conceptualized as a motor disorder, but nonmotor symptoms also manifest in the disease and significantly reduce quality of life. Anxiety and cognitive dysfunction are prevalent nonmotor symptoms, even in early disease stages, but the relation between these symptoms remains poorly understood. We examined self-reported anxiety and neurocognitive function, indexed by measures of executive function (set-shifting and phonemic fluency), categorical fluency, and attention/working memory. We hypothesized that anxiety would correlate with cognitive performance. METHOD: The Beck Anxiety Inventory and cognitive tests (Trail Making, Verbal Fluency, Digit Span) were administered to 77 nondemented adults with mild to moderate idiopathic PD (39 men, 38 women; Mage = 62.9 years). RESULTS: Higher anxiety was associated with more advanced disease stage and severity and with poorer set-shifting when using a derived metric to account for motoric slowing. Depression correlated with greater anxiety and disease severity, but not with cognitive performance. CONCLUSIONS: Our findings support the association of anxiety with a specific domain of executive function, set-shifting, in nondemented individuals with mild to moderate PD, raising the possibility that treatment of anxiety may alleviate aspects of executive dysfunction in this population.Accepted manuscrip

Cognitive impairment in Parkinson's disease without dementia

Some degree of cognitive impairment appears frequently in Parkinson's disease (PD) patients, even at the onset of the disease. However, due to the heterogeneity of the patients and the lack of standardized assessment batteries, it remains unclear which capacities are primarily affected by this disease. Fifty PD patients were assessed with 15 tests including executive functions, attention, temporal and spatial orientation, memory, and language tasks. Their results were compared with those of 42 age‐ and education‐matched healthy seniors. Semantic fluency, along with visual search appeared to be the most discriminant tasks, followed by temporal orientation and face naming, as well as action naming and immediate recall. PD patients studied showed an impairment of frontal‐ to posterior‐dependent capacities. Executive functions, attention, and recall tasks appeared to be significantly impaired in the patients. Nevertheless, significantly poor scores in tasks like action and face naming, as well as semantic fluency, also reveal a mainly semantic deficit