Post-Cueing Deficits with Maintained Cueing Benefits in Patients with Parkinson's Disease Dementia

In Parkinson's disease (PD), internal cueing mechanisms are impaired leading to symptoms like hypokinesia. However, external cues can improve movement execution by using cortical resources. These cortical processes can be affected by cognitive decline in dementia. It is still unclear how dementia in PD influences external cueing. We investigated a group of 25 PD patients with dementia (PDD) and 25 non-demented PD patients (PDnD) matched by age, sex, and disease duration in a simple reaction time task using an additional acoustic cue. PDD patients benefited from the additional cue in similar magnitude as did PDnD patients. However, withdrawal of the cue led to a significantly increased reaction time in the PDD group compared to the PDnD patients. Our results indicate that even PDD patients can benefit from strategies using external cue presentation but the process of cognitive worsening can reduce the effect when cues are withdrawn

Quantifying activities of daily living impairment in Parkinson’s disease using the Functional Activities Questionnaire

Objective Cognitive-driven activity of daily living (ADL) impairment in Parkinson’s disease (PD) is increasingly discussed as prodromal marker for dementia. Diagnostic properties of assessments for this specifc ADL impairment are sparsely investigated in PD. The ability of the Functional Activities Questionnaire (FAQ) for diferentiating between PD patients with normal cognition and with mild cognitive impairment (PD-MCI), according to informant and self-reports, was examined. Global cognitive function in groups with and without mild ADL impairment was compared according to diferent cut-ofs. Methods Multicenter data of 589 patients of an international cohort (CENTRE-PD) were analyzed. Analyses were run separately for informant-rated and self-rated FAQ. Receiver operating characteristic (ROC) analysis was conducted to defne the optimal FAQ cut-of for PD-MCI (≥1), and groups were additionally split according to reported FAQ cut-ofs for PD-MCI in the literature (≥3,≥5). Binary logistic regressions examined the efect of the Montreal Cognitive Assessment (MoCA) score in PD patients with and without mild ADL impairment. Results Two hundred and twenty-fve (38.2%) patients were classifed as PD-MCI. For all three cut-of values, sensitivity was moderate to low (0.54) with a tendency of higher values for self-reported defcits. For the self-report, the cut-of≥3 showed a signifcant efect of the MoCA (B= −0.31, p=0.003), where FAQ≥3 patients had worse cognition. No efect for group diferences based on informant ratings was detected. Conclusion Our data argue that self-reported ADL impairments assessed by the FAQ show a relation to the severity of cognitive impairment in PD

Influence of Different Cut-Off Values on the Diagnosis of Mild Cognitive Impairment in Parkinson's Disease

Comparable to Alzheimer’s disease, mild cognitive impairment in Parkinson’s disease (PD-MCI) is associated with an increased risk for dementia. However different definitions of PD-MCI may have varying predictive accuracy for dementia. In a cohort of 101 nondemented Parkinson patients who underwent neuropsychological testing, the frequency of PD-MCI subjects and PDMCI subtypes (i.e., amnestic/nonamnestic) was determined by use of varying healthy population-based cut-off values. We also investigated the association between defined PD-MCI groups and ADL scales. Varying cut-off values for the definition of PD-MCI were found to affect frequency of PD-MCI subjects (9.9%–92.1%) and, maybe more important, lead to a “shift” of proportion of detected PD-MCI subtypes especially within the amnestic single-domain subtype. Models using a strict cut-off value were significantly associated with lower ADL scores. Thus, the use of defined cut-off values for the definition of PD-MCI is highly relevant for comparison purposes. Strict cut-off values may have a higher predictive value for dementia

Validation of conversion between Mini-Mental State Examination and Montreal Cognitive Assessment

Introduction: Harmonizing data across cohorts is important for validating findings or combining data in meta‐analyses. We replicate and validate a previous conversion of MoCA to MMSE in PD. Methods: We used five studies with 1,161 PD individuals and 2,091 observations measured with both the MoCA and MMSE. We compared a previously published conversion table using equipercentile equating with log‐linear smoothing to our internally derived scores. Results: Both conversions found good agreement within and across the studies when comparing true and converted MMSE (mean difference: 0.05; standard deviation: 1.84; median difference: 0; interquartile range: –1 to 1, using internal conversion). Conclusions: These results show that one can get a reliable and valid conversion between two commonly used measures of cognition in PD studies. These approaches need to be applied to other scales and domains to enable large‐scale collaborative analyses across multiple PD cohorts. © 2016 International Parkinson and Movement Disorder Society </p

Instrumented Functional Reach Test Differentiates Individuals at High Risk for Parkinson's Disease from Controls

The functional reach (FR) test as a complex measure of balance including limits of stability has been proven to differentiate between patients with Parkinson's disease (PD) and controls (CO). Recently, it has been shown that the instrumentation of the FR (iFR) with a wearable sensor may increase this diagnostic accuracy. This cross-sectional study aimed at investigating whether the iFR has the potential to differentiate individuals with high risk for PD (HRPD) from CO, as the delineation of such individuals would allow for, e.g., early neuromodulation. Thirteen PD patients, 13 CO, and 31 HRPD were investigated. HRPD was defined by presence of an enlarged area of hyperechogenicity in the mesencephalon on transcranial sonography and either one motor sign or two risk and prodromal markers of PD. All participants were asked to reach with their right arm forward as far as possible and hold this position for 10 s. During this period, sway parameters were assessed with an accelerometer (Dynaport, McRoberts) worn at the lower back. Extracted parameters that differed significantly between PD patients and CO in our cohort [FR distance (shorter in PD), anterior-posterior and mediolateral acceleration (both lower in PD)] as well as JERK, which has been shown to differentiate HRPD from CO and PD in a previous study, were included in a model, which was then used to differentiate HRPD from CO. The model yielded an area under the curve of 0.77, with a specificity of 85%, and a sensitivity of 74%. These results suggest that the iFR can contribute to an assessment panel focusing on the definition of HRPD individuals

Effect of Fear of Falling on Turning Performance in Parkinson's Disease in the Lab and at Home

Background: Parkinson's disease (PD) is a neurodegenerative movement disorder associated with gait and balance problems and a substantially increased risk of falling. Falls occur often during complex movements, such as turns. Both fear of falling (FOF) and previous falls are relevant risk factors for future falls. Based on recent studies indicating that lab-based and home assessment of similar movements show different results, we hypothesized that FOF and a positive fall history would influence the quantitative turning parameters differently in the laboratory and home. Methods: Fifty-five PD patients (43 underwent a standardized lab assessment; 40 were assessed over a mean of 12 days at home with approximately 10,000 turns per participant; and 28 contributed to both assessments) were classified regarding FOF and previous falls as "vigorous" (no FOF, negative fall history), "anxious" (FOF, negative fall history), "stoic" (no FOF, positive fall history) and "aware" (FOF, positive fall history). During the assessments, each participant wore a sensor on the lower back. Results: In the lab assessment, FOF was associated with a longer turning duration and lowered maximum and middle angular velocities of turns. In the home evaluations, a lack of FOF was associated with lowered maximum and average angular velocities of turns. Positive falls history was not significantly associated with turning parameters, neither in the lab nor in the home. Conclusion: FOF but not a positive fall history influences turning metrics in PD patients in both supervised and unsupervised environments, and this association is different between lab and home assessments. Our findings underline the relevance of comprehensive assessments including home-based data collection strategies for fall risk evaluation

Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study

BACKGROUND: Mutations in the gene coding for glucocerebrosidase (GBA), which metabolizes glucosylceramide (a monohexosylceramide) into glucose and ceramide, is the most common genetic risk factor for sporadic Parkinson's disease (PD). GBA mutation carriers are more likely to have an earlier age of onset and to develop cognitive impairment and dementia. We hypothesized that plasma levels of lipids involved in ceramide metabolism would also be altered in PD non-GBA mutation carriers and associated with worse cognition. METHODS: Plasma ceramide, monohexosylceramide, and lactosylceramide levels in 26 cognitively normal PD patients, 26 PD patients with cognitive impairment or dementia, and 5 cognitively normal non-PD controls were determined by LC/ESI/MS/MS. RESULTS: Levels of all lipid species were higher in PD patients versus controls. Among PD patients, levels of ceramide C16:0, C18:0, C20:0, C22:0, and C24:1 and monohexosylceramide C16:0, C20:0 and C24:0 species were higher (all P<0.05) in those with versus without cognitive impairment. CONCLUSION: These results suggest that plasma ceramide and monohexosylceramide metabolism is altered in PD non-GBA mutation carriers and that higher levels are associated with worse cognition. Additional studies with larger sample sizes, including cognitively normal controls, are needed to confirm these findings

Prodromal Markers in Parkinson's Disease:Limitations in Longitudinal Studies and Lessons Learned

A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies

Phylogenetic relationships of species of Raymunida (Decapoda: Galatheidae) based on morphology and mitochondrial cytochrome oxidase sequences, with the recognition of four new species

19 pages.-- RECEIVED: 10 April 2000, ACCEPTED: 8 November 2000.The species of the genus Raymunida from the Pacific and Indian oceans are revised using morphological characters and the mitochondrial cytochrome oxidase subunit I sequences. Four new species are described (R. confundens, R. dextralis, R. erythrina, and R. insulata), and the status of R. bellior and R. elegantissima are revised. The species of Raymunida can be identified by subtle morphological characters, which match differences in mitochondrial nucleotide sequences. Therefore, the sequence divergences confirm the specific and phylogenetic value of some morphological characters (e.g., length of the mesial spine on the basal antennal segment, length of the walking legs). Furthermore, they confirm the importance of the color pattern as a diagnostic character. The widespread species (R. elegantissima), known from the Philippines to Fiji, shows minimal divergence between specimens from different localities (maximum of 3 nucleotide differences or 0.2% mean divergence). The phylogenetic reconstruction agreed with the monophyletic condition of Raymunida and its differentiation with respect to the genus Munida (in which Raymunida species had previously been included) and Agononida.Peer reviewe