Dimensions of apathy in Parkinson's disease.

INTRODUCTION: Apathy is one of the most common neuropsychiatric manifestations in Parkinson's disease (PD). Recent proposals consider apathy as a multidimensional construct, which can manifest in behavioral, cognitive, emotional, and/or social dimensions. Apathy also overlaps conceptually and clinically with other non-motor comorbidities, particularly depression. Whether all of these dimensions are applicable to the apathetic syndrome experienced by people with PD is unclear. In the present study, we investigated the multidimensional pattern of apathy associated with PD, using the recently developed Apathy Motivation Index (AMI) which probes behavioral, emotional, and social apathy dimensions. We then examined the relationship between these dimensions and other features of PD commonly associated with apathy, including depression, anxiety, cognition, and motor state. METHODS: A total of 211 participants were identified from the New Zealand Brain Research Institute (NZBRI) longitudinal PD cohort. One hundred eight patients and 45 controls completed the AMI, administered as an online questionnaire, and additional assessments including neuropsychiatric, neuropsychological, and motor scores. The pattern of dimensional apathy in PD was assessed using a repeated-measured analysis of variance, while simple linear regressions were performed to evaluate relationships between these dimensions and other variables. RESULTS: We found a significant interaction between group (PD versus control) and apathy subscale, driven mainly by higher levels of social and behavioral-but not emotional-apathy in those with PD. This result was strikingly similar to a previous study investigating social apathy in PD. Distinct patterns of dimensional apathy were associated with depression and anxiety, with social and behavioral apathy positively associated with depression, and emotional apathy negatively associated with anxiety. CONCLUSION: This work provides further evidence for a distinct pattern of apathy in people with PD in which deficits manifest in some-but not all-dimensions of motivated behavior. It emphasizes the importance of considering apathy as a multidimensional construct in clinical and research settings.

Higher perceived stress and exacerbated motor symptoms in Parkinson's disease during the COVID-19 lockdown in New Zealand.

AIMS: Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown. METHODS: During lockdown, 134 participants with PD and 49 controls completed a survey assessing perceived stress, self-reported changes in PD motor symptoms and physical activity duration and intensity prior to and during lockdown. RESULTS: Perceived stress was higher in PD than controls, and in those reporting a worsening of tremor, balance/gait, dyskinesia and bradykinesia compared to those indicating no change during the COVID-19 lockdown. These effects were not modulated by physical activity. CONCLUSIONS: Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD.

Neuropsychiatric Symptoms Are Associated with Dementia in Parkinson's Disease but Not Predictive of it.

BACKGROUND: Neuropsychiatric symptoms in Parkinson's disease (PD) may increase dementia (PDD) risk. The predictive value of these symptoms, however, has not been compared to clinical and demographic predictors of future PDD. OBJECTIVES: Determine if neuropsychiatric symptoms are useful markers of PDD risk. METHODS: 328 PD participants completed baseline neuropsychiatric and MDS-Task Force-Level II assessments. Of these, 202 non-demented individuals were followed-up over a four-years period to detect conversion to PDD; 51 developed PDD. ROC analysis tested associations between baseline neuropsychiatric symptoms and future PDD. The probability of developing PDD was also modeled as a function of neuropsychiatric inventory (NPI)-total score, PD Questionnaire (PDQ)-hallucinations, PDQ-anxiety, and contrasted to cognitive ability, age, and motor function. Leave-one-out information criterion was used to evaluate which models provided useful information when predicting future PDD. RESULTS: The PDD group experienced greater levels of neuropsychiatric symptoms compared to the non-PDD groups at baseline. Few differences were found between the PD-MCI and PD-N groups. Six neuropsychiatric measures were significantly, but weakly, associated with future PDD. The strongest was NPI-total score: AUC = 0.66 [0.57-0.75]. There was, however, no evidence it contained useful out-of-sample predictive information of future PDD (delta ELPD = 1.8 (SD 2.5)); Similar results held for PDQ-hallucinations and PDQ-anxiety. In contrast, cognitive ability (delta ELPD = 36 (SD 8)) and age (delta ELPD = 11 (SD 5)) provided useful predictive information of future PDD. CONCLUSIONS: Cognitive ability and age strongly out-performed neuropsychiatric measures as markers of developing PDD within 4 years. Therefore, neuropsychiatric symptoms do not appear to be useful markers of PDD risk.

Beta Amyloid Deposition Is Not Associated With Cognitive Impairment in Parkinson's Disease.

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.

Altered grey matter volume, perfusion and white matter integrity in very low birthweight adults.

This study examined the long-term effects of being born very-low-birth-weight (VLBW, <1500 g) on adult cerebral structural development using a multi-method neuroimaging approach. The New Zealand VLBW study cohort comprised 413 individuals born VLBW in 1986. Of the 338 who survived to discharge, 229 were assessed at age 27-29 years. Of these, 150 had a 3 T MRI scan alongside 50 healthy term-born controls. The VLBW group included 53/57 participants born <28 weeks gestation. MRI analyses included: a) structural MRI to assess grey matter (GM) volume and cortical thickness; b) arterial spin labelling (ASL) to quantify GM perfusion; and c) diffusion tensor imaging (DTI) to measure white matter (WM) integrity. Compared to controls, VLBW adults had smaller GM volumes within frontal, temporal, parietal and occipital cortices, bilateral cingulate gyri and left caudate, as well as greater GM volumes in frontal, temporal and occipital areas. Thinner cortex was observed within frontal, temporal and parietal cortices. VLBW adults also had less GM perfusion within limited temporal areas, bilateral hippocampi and thalami. Finally, lower fractional anisotropy (FA) and axial diffusivity (AD) within principal WM tracts was observed in VLBW subjects. Within the VLBW group, birthweight was positively correlated with GM volume and perfusion in cortical and subcortical regions, as well as FA and AD across numerous principal WM tracts. Between group differences within temporal cortices were evident across all imaging modalities, suggesting that the temporal lobe may be particularly susceptible to disruption in development following preterm birth. Overall, findings reveal enduring and pervasive effects of preterm birth on brain structural development, with individuals born at lower birthweights having greater long-term neuropathology.

The Symbol-Digit Modalities Test in Mild Cognitive Impairment: Evidence from Parkinson's Disease Patients.

BACKGROUND: The evaluation process of the performance of the symbol-digit modalities test (SDMT) has focused much on numerical scores paying only little attention to the qualitative aspects of performance. Incorporating the gaze analysis technique, we aimed to investigate the performance of Parkinson's disease (PD) patients on the written SDMT task. METHODS: Twelve patients with PD and normal cognition (PD-N), 11 with PD and mild cognitive impairment (PD-MCI), and 13 healthy participants (NC) controlled for age, sex and education were recruited. RESULTS: PD-MCI participants achieved significantly lower scores than NC and PD-N participants. Eye-movement parameters, however, did not differ among the study groups, and were not correlated with task performance. CONCLUSIONS: Impaired performance on the SDMT by PD-MCI participants despite relatively preserved oculomotor performance indicates that lower SDMT scores are not due - even in part - to visuomotor impairments otherwise seen in PD patients.