Compensatory shifts in visual perception are associated with hallucinations in Lewy body disorders

Abstract Visual hallucinations are a common, distressing, and disabling symptom of Lewy body and other diseases. Current models suggest that interactions in internal cognitive processes generate hallucinations. However, these neglect external factors. Pareidolic illusions are an experimental analogue of hallucinations. They are easily induced in Lewy body disease, have similar content to spontaneous hallucinations, and respond to cholinesterase inhibitors in the same way. We used a primed pareidolia task with hallucinating participants with Lewy body disorders (n = 16), non-hallucinating participants with Lewy body disorders (n = 19), and healthy controls (n = 20). Participants were presented with visual “noise” that sometimes contained degraded visual objects and were required to indicate what they saw. Some perceptions were cued in advance by a visual prime. Results showed that hallucinating participants were impaired in discerning visual signals from noise, with a relaxed criterion threshold for perception compared to both other groups. After the presentation of a visual prime, the criterion was comparable to the other groups. The results suggest that participants with hallucinations compensate for perceptual deficits by relaxing perceptual criteria, at a cost of seeing things that are not there, and that visual cues regularize perception. This latter finding may provide a mechanism for understanding the interaction between environments and hallucinations

Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease

Objective: Rapid eye movement sleep behavior disorder (RBD) is common in Parkinson disease (PD), but its relationship to the varied neurotransmitter deficits of PD and prognostic significance remain incompletely understood. RBD and cholinergic system degeneration are identified independently as risk factors for cognitive impairment in PD. We aimed to assess the association between cholinergic denervation and symptoms of RBD in PD patients without dementia. Methods: Eighty subjects with PD without dementia (age, 64.6 ± 7.0 years; range, 50–82 years; 60 males, 20 females; mean Montreal Cognitive Assessment Test [MoCA] score, 26.2 ± 2.1; range 21–30) underwent clinical assessment, neuropsychological testing, and [ 11 C]methylpiperidyl propionate acetylcholinesterase and [ 11 C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 positron emission tomography (PET) imaging. 11 C3‐Amino‐4‐(2‐dimethylaminomethyl‐phenylsulfaryl)‐benzonitrile (DASB) serotonin transporter PET imaging was performed in a subset of 35 subjects. The presence of RBD symptoms was determined using the Mayo Sleep Questionnaire. Results: Twenty‐seven of 80 subjects (33.8%) indicated a history of RBD symptoms. Subjects with and without RBD symptoms showed no significant differences in age, motor disease duration, MoCA, Unified Parkinson Disease Rating Scale motor scores, or striatal DTBZ binding. Subjects with RBD symptoms, in comparison to those without, exhibited decreased neocortical, limbic cortical, and thalamic cholinergic innervation (0.0213 ± 0.0018 vs 0.0236 ± 0.0022, t = 4.55, p < 0.0001; 0.0388 ± 0.0029 vs 0.0423 ± 0.0058, t = 2.85, p = 0.0056; 0.0388 ± 0.0025 vs 0.0427 ± 0.0042, t = 4.49, p < 0.0001, respectively). Brainstem and striatal DASB binding showed no significant differences between groups. Interpretation: The presence of RBD symptoms in PD is associated with relative neocortical, limbic cortical, and thalamic cholinergic denervation although not with differential serotoninergic or nigrostriatal dopaminergic denervation. The presence of RBD symptoms may signal cholinergic system degeneration. ANN NEUROL 2012;Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91165/1/22691_ftp.pd

Neural correlates of attention-executive dysfunction in lewy body dementia and Alzheimer's disease.

Attentional and executive dysfunction contribute to cognitive impairment in both Lewy body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention (alerting, orienting, and executive/conflict function) in 23 patients with Alzheimer's disease, 32 patients with Lewy body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto-parieto-occipital network activation in all groups, Alzheimer's disease and Lewy body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention-executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases.This work was supported by an Intermediate Clinical Fellowship . Grant Number: (WT088441MA) to John‐Paul Taylor the National Institute for Health Research (NIHR), and Newcastle Biomedical Research Unit (BRU) based at Newcastle upon Tyne Hospitals NHS Trust, Newcastle University

Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: A systematic review

Introduction Neuropsychiatric symptoms are one of the most common non-motor symptoms in Parkinson's disease (PD). These symptoms have a negative impact on daily living activities and cognitive abilities. This review will be centred on published articles which focused on clarifying the cognitive and neuroanatomical features associated with the appearance of specific neuropsychiatric symptoms in this disease. Methods All articles indexed in the Web of Science and PubMed databases were reviewed for potential inclusion in October 2014. In the first stage of the review, we identified 41 articles that investigated neuropsychiatric symptoms and cognitive impairments in PD. In the second stage, there were 26 published articles on the neural bases of neuropsychiatric symptoms in PD. Results The main findings revealed that executive dysfunctions were common in patients with depression, apathy, visual hallucinations (VH), impulse control disorders (ICDs) and anxiety, whereas, memory deficits were associated mainly with depression and VH. Imaging studies have shown that frontal lobe atrophy was frequently observed in patients with depression, apathy, VH and ICDs. Conclusion This review gives a snapshot of those cognitive and neural correlates of neuropsychiatric symptoms in PD. Methodological shortcoming in the available studies were identified, however, of which the most critical appeared neglecting the presence of multiple neuropsychiatric symptoms in some of the patients included in studies of specific individual symptoms. Additionally, in most studies only patients in the moderate to severe stages were included which limits possible inferences to the early stage of the disease

Cognitive impairment in Parkinson's disease:impact on quality of life of carers

Background: The quality of life (QoL) of informal caregivers of people with Parkinson’s disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers. Methods: Approximately 36months after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains. Results: Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (n= 9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (n= 18) or normal cognition (n= 39) carers (p<0.01). Conclusions: Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self-efficacy in carers may improve carer QoL.Full Tex

Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities

Effect of different exercise programs on the psychological and cognitive functions of people with Parkinson's disease

The purpose of this study was to analyze the effect of different exercise programs on the psychological and cognitive functions in patients with Parkinson's disease (PD). Forty-five patients with PD participated in the study. The participants were randomized in three intervention programs: Group-1 (n=15, cognitive-activities), Group-2 (n=15, multimodal exercise) and Group-3 (n=15, exercises for posture and gait). The clinical, psychological and cognitive functions were assessed before and after 4 months of intervention. Univariate analysis did not reveal significant interactions between groups and time (p>0.05). However, univariate analysis for time revealed differences in stress level and memory. Participants showed less physical stress (p<0.01) and overall stress (p < 0.04) and higher performance in episodic declarative memory (p < 0.001) after exercise. These findings suggest that group work with motor or non-motor activities can improve cognitive and psychological functions of patients with PD