The Movement Disorder Society Task Force (MDS-TF) has proposed diagnostic criteria for mild cognitive impairment in Parkinson’s disease (PD-MCI). We hypothesized that the risk of dementia (PDD) varies across the different cutoff schemes allowed. A longitudinal study followed 121 non-demented PD patients for up to 4.5 years. In Part One, unique groups of patients were identified as PD-MCI at baseline using the MDS-TF requirement of two impaired cognitive test scores, with both scores classified as impaired at either (i) 2 s.d., (ii) 1.5 s.d. or (iii) 1 s.d. below normative data; relative risk (RR) of PDD was assessed at each criterion. In Part Two, the whole sample was reassessed and (i) RR of PDD determined when two impairments at 1.5 s.d. existed within a single cognitive domain, followed by (ii) RR of PDD in the unique group whose two impairments at 1.5 s.d. did not exist within a single domain (i.e., only across two domains). Twenty-one percent of patients converted to PDD. Part One showed that the 1.5 s.d. criterion at baseline is optimal to maximize progression to PDD over 4 years. Part Two, however, showed that the 1.5 s.d. cutoff produced a high RR of PDD only when two impairments were identified within a single cognitive domain (7.2, 95% confidence interval (CI)=3.4–16.6, P<0.0001; 51% converted). The RR when the 1.5 s.d. impairments occurred only across two different domains, was nonsignificant (1.7, CI=0.5–7.4, P=0.13; 11% converted) and similar to using a 1 s.d. criterion (1.9, CI=0.3–4.3, P=0.13; 8% converted). If the intent of a PD-MCI diagnosis is to detect increased risk of PDD in the next 4 years, optimal criteria should identify at least two impairments at 1.5 s.d. within a single cognitive domain.

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Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD

The extent to which Alzheimer neuropathology, particularly the accumulation of misfolded beta-amyloid, contributes to cognitive decline and dementia in Parkinson's disease (PD) is unresolved. Here, we used Florbetaben PET imaging to test for any association between cerebral amyloid deposition and cognitive impairment in PD, in a sample enriched for cases with mild cognitive impairment. This cross-sectional study used Movement Disorders Society level II criteria to classify 115 participants with PD as having normal cognition (PDN, n = 23), mild cognitive impairment (PD-MCI, n = 76), or dementia (PDD, n = 16). We acquired 18F-Florbetaben (FBB) amyloid PET and structural MRI. Amyloid deposition was assessed between the three cognitive groups, and also across the whole sample using continuous measures of both global cognitive status and average performance in memory domain tests. Outcomes were cortical FBB uptake, expressed in centiloids and as standardized uptake value ratios (SUVR) using the Centiloid Project whole cerebellum region as a reference, and regional SUVR measurements. FBB binding was higher in PDD, but this difference did not survive adjustment for the older age of the PDD group. We established a suitable centiloid cut-off for amyloid positivity in Parkinson's disease (31.3), but there was no association of FBB binding with global cognitive or memory scores. The failure to find an association between PET amyloid deposition and cognitive impairment in a moderately large sample, particularly given that it was enriched with PD-MCI patients at risk of dementia, suggests that amyloid pathology is not the primary driver of cognitive impairment and dementia in most patients with PD.

BackgroundThere is limited evidence on caregiver outcomes associated with mild cognitive impairment in patients with Parkinson’s disease (PD-MCI) and the coping strategies used by these caregivers.MethodsTo investigate this relationship, we examined levels of burden, depression, anxiety, coping strategies and positive aspects of caregiving in the informal caregivers of 96 PD patients. The PD patients were classified using MDS-Task Force Level II criteria as showing either normal cognition (PD-N; n = 51), PD-MCI (n = 30) or with dementia (PDD; n = 15).ResultsMean Zarit Burden Interview (ZBI) score increased significantly between carers of PD-N (M = 13.39, SD = 12.22) compared to those of PD-MCI patients (M = 22.00, SD = 10.8), and between carers of PD-MCI and PDD patients (M = 29.33, SD = 9.59). Moreover, the proportion of carers showing clinically significant levels of burden (ZBI score ≥ 21) also increased as the patients’ cognitive status declined (18% for PD-N; 60% for PD-MCI; and 80% for PDD) and was mirrored by an increasing amount of time spent providing care by the caregivers. Caregiver ZBI score was independent of patient neuropsychiatric symptoms, motor function, disease duration and time that caregivers spent caregiving. Caregiver use of different coping strategies increased with worsening cognition. However, we found only equivocal evidence that the use of problem-focused, emotion-focused and dysfunctional coping mediated the association between patient cognitive status and caregiver burden, because the inverse models that used caregiver burden as the mediator were also significant.ConclusionsThe study highlights the impact of Parkinson’s disease on those providing care when the patient’s cognition is poor, including those with MCI. Caregiver well-being has important implications for caregiver support, nursing home placement and disease course.Electronic supplementary materialThe online version of this article (doi:10.1186/s40035-017-0085-5) contains supplementary material, which is available to authorized users.

The three-class approach is used for progressive disorders when clinicians and researchers want to diagnose or classify subjects as members of one of three ordered categories based on a continuous diagnostic marker. The decision thresholds or optimal cut-off points required for this classification are often chosen to maximize the generalized Youden index (Nakas et al., Stat Med 2013; 32: 995-1003). The effectiveness of these chosen cut-off points can be evaluated by estimating their corresponding true class fractions and their associated confidence regions. Recently, in the two-class case, parametric and non-parametric methods were investigated for the construction of confidence regions for the pair of the Youden-index-based optimal sensitivity and specificity fractions that can take into account the correlation introduced between sensitivity and specificity when the optimal cut-off point is estimated from the data (Bantis et al., Biomet 2014; 70: 212-223). A parametric approach based on the Box-Cox transformation to normality often works well while for markers having more complex distributions a non-parametric procedure using logspline density estimation can be used instead. The true class fractions that correspond to the optimal cut-off points estimated by the generalized Youden index are correlated similarly to the two-class case. In this article, we generalize these methods to the three- and to the general k-class case which involves the classification of subjects into three or more ordered categories, where ROC surface or ROC manifold methodology, respectively, is typically employed for the evaluation of the discriminatory capacity of a diagnostic marker. We obtain three- and multi-dimensional joint confidence regions for the optimal true class fractions. We illustrate this with an application to the Trail Making Test Part A that has been used to characterize cognitive impairment in patients with Parkinson's disease.

Progressive cognitive decline is a feature of Huntington’s disease (HD), an inherited neurodegenerative movement disorder. Comprehensive neuropsychological testing is the ‘gold standard’ to establish cognitive status but is often impractical in time-constrained clinics. The study evaluated the utility of brief cognitive tests (MMSE and MoCA), UHDRS measures and a comprehensive neuropsychological tests battery in monitoring short-term disease progression in HD. Twenty-two manifest HD patients and 22 matched controls were assessed at baseline and 12-month. A linear mixed-effect model showed that although the HD group had minimal change in overall global cognition after 12 months, they did show a significant decline relative to the control group. The controls exhibited a practice effect in most of the cognitive domain scores over time. Cognitive decline at 12-month in HD was found in the executive function domain but the effect of this on global cognitive score was masked by the improvement in their language domain score. The varying practice effects by cognitive domain with repeated testing indicates the importance of comparing HD patients to control group in research trials and that cognitive progression over 12 months in HD should not be judged by changes in global cognitive score. The three brief cognitive tests effectively described cognition of HD patients on cross-sectional analysis. The UHDRS cognitive component, which focuses on testing executive function and had low variance over time, is a more reliable brief substitute for comprehensive neuropsychological testing than MMSE and MoCA in monitoring cognitive changes in HD patients after 12 months.

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