Frontal and associative visual areas related to visual hallucinations in dementia with Lewy bodies and Parkinson's disease with dementia

Visual Hallucinations (VH) are among the core features of Dementia with Lewy Bodies (DLB), but are also very frequent in demented patients with Parkinson's Disease (PDD). The purpose of this study was to investigate the pattern of gray matter and cognitive impairment underlying VH in DLB and PDD. We applied voxel‐based morphometry and behavioral assessment to 12 clinically diagnosed DLB patients and 15 PDD patients. Subjects with VH showed greater gray matter loss than non‐hallucinators, specifically in the right inferior frontal gyrus (BA 45) in the DLB patients and in the left orbitofrontal lobe (BA 10) in the PDD patients. Comparing the two subgroups with VH, DLB patients had greater decrease of the bilateral premotor area (BA 6) than PDD patients. Furthermore, decreased volume in associative visual areas, namely left precuneus and inferior frontal lobe, correlated with VH in the DLB but not in PDD patients. VH were related to impaired verbal fluency, inhibitory control of attention and visuoperception in the DLB group and to visual memory in the PDD group. In conclusion, DLB and PDD patients with VH had more frontal gray matter atrophy than non‐hallucinators, the impairment being greater in the DLB group. The patterns of structural and functional correlations were different in both pathologies. © 2010 Movement Disorder Society     

Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease

We aimed to determine prospectively whether rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, provided benefits in patients with and without visual hallucinations in a population with dementia associated with Parkinson's disease (PDD). This was a 24‐week double‐blind placebo‐controlled study. Primary efficacy measures were the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS‐cog) and Alzheimer's Disease Cooperative Study–Clinician's Global Impression of Change (ADCS‐CGIC). Secondary efficacy measures included activities of daily living, behavioral symptoms, and executive and attentional functions. Patients were stratified according to the presence of visual hallucinations at baseline. The study included 188 visual hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided benefits in both visual hallucinators and nonvisual hallucinators. Absolute responses to rivastigmine on the ADAS‐cog were comparable over 6 months, although rivastigmine–placebo differences tended to be larger in visual hallucinators (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS‐CGIC, differences between rivastigmine and placebo were 0.5 in visual hallucinators (P = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits on all secondary efficacy measures, and placebo declines and treatment differences were more marked in visual hallucinators. Adverse events were reported more frequently by rivastigmine‐treated patients, although this difference was less marked in visual hallucinators. Visual hallucinations appear to predict more rapid decline and possibly greater therapeutic benefit from rivastigmine treatment in PDD. © 2006 Movement Disorder Society     

Visual object recognition and attention in Parkinson's disease patients with visual hallucinations

Visual hallucinations (VH) are common in Parkinson's disease (PD) and are hypothesized to be due to impaired visual perception and attention deficits. We investigated whether PD patients with VH showed attention deficits, a more specific impairment of higher order visual perception, or both. Forty‐two volunteers participated in this study, including 14 PD patients with VH, 14 PD patients without VH and 14 healthy controls (HC), matched for age, gender, education level and for level of executive function. We created movies with images of animals, people, and objects dynamically appearing out of random noise. Time until recognition of the image was recorded. Sustained attention was tested using the Test of Attentional Performance. PD patients with VH recognized all images but were significantly slower in image recognition than both PD patients without VH and HC. PD patients with VH showed decreased sustained attention compared to PD patients without VH who again performed worse than HC. In conclusion, the recognition of objects is intact in PD patients with VH; however, these patients where significantly slower in image recognition than patients without VH and HC, which was not explained by executive dysfunction. Both image recognition speed and sustained attention decline in PD, in a more progressive way if VH start to occur. © 2008 Movement Disorder Society     

Visual hallucinations in Parkinson's disease: Theoretical models

One of the most challenging tasks in neuroscience is to be able to meaningfully connect information across the different levels of investigation, from molecular or structural biology to the resulting behavior and cognition. Visual hallucinations are a frequent occurrence in Parkinson's disease and significantly contribute to the burden of the disease. Because of the widespread pathological processes implicated in visual hallucinations in Parkinson's disease, a final common mechanism that explains their manifestation will require an integrative approach, in which consideration is taken across all complementary levels of analysis. This review considers the leading hypothetical frameworks for visual hallucinations in Parkinson's disease, summarizing the key aspects of each in an attempt to highlight the aspects of the condition that such a unifying hypothesis must explain. These competing hypotheses include implications of dream imagery intrusion, deficits in reality monitoring, and impairments in visual perception and attention. © 2014 International Parkinson and Movement Disorder Society     

Neuropsychological deficits in Parkinson's disease patients with visual hallucinations.

Recent neuropathological and neuroimaging studies suggest the involvement of several temporal regions in Parkinson's disease (PD) patients with visual hallucinations (VH). We examined 24 nondemented PD patients with VH, 21 PD patients without VH, and 21 healthy controls using a battery of tests assessing different aspects of temporal lobe function. PD patients with VH showed poorer performance in language, verbal learning, semantic fluency, and visuoperceptive functions compared to controls and PD patients without VH. Differences in verbal learning and visuoperceptive functions were independent of general cognitive status, disease severity, and depression. We suggest that a wide range of neuropsychological deficits can contribute to the emergence of VH in PD.     

Visual complaints and visual hallucinations in Parkinson's disease

BackgroundVisual symptoms are common in Parkinson's disease (PD) and are frequently under-diagnosed. The detection of visual symptoms is important for differential diagnosis and patient management.AimTo establish the prevalence of recurrent visual complaints (RVC) and recurrent visual hallucinations (RVH) and to investigate their interaction in PD patients and controls.MethodsThis cross-sectional study included 88 PD patients and 90 controls. RVC and RVH were assessed with a visual symptom questionnaire and the North-East-Visual-Hallucinations-Interview (NEVHI).ResultsDouble vision (PD vs. Controls: 18.2% vs. 1.3%; p < 0.001), misjudging objects when walking (PD vs. Controls: 12.5% vs. 1.3%; p < 0.01), words moving whilst reading (PD vs. Controls: 17.0% vs. 1.3%; p < 0.001) and freezing in narrow spaces (PD vs. Controls: 30.7% vs. 0%; p < 0.001) were almost exclusively found in PD patients. The same was true for recurrent complex visual hallucinations and illusions (PD vs. Controls: both 17.0% vs. 0%; p < 0.001). Multiple RVC (43.2% vs. 15.8%) and multiple RVH (29.5% vs. 5.6%) were also more common in PD patients (both p < 0.001). RVC did not predict recurrent complex visual hallucinations; but double vision (p = 0.018, R² = 0.302) and misjudging objects (p = 0.002, R² = 0.302) predicted passage hallucinations. Misjudging objects also predicted the feeling of presence (p = 0.010, R² = 0.321).ConclusionsMultiple and recurrent visual symptoms are common in PD. RVC emerged as risk factors predictive of the minor forms of hallucinations, but not recurrent complex visual hallucinations.     

Visual symptoms in Parkinson's disease and Parkinson's disease dementia

Visual symptoms are common in PD and PD dementia and include difficulty reading, double vision, illusions, feelings of presence and passage, and complex visual hallucinations. Despite the established prognostic implications of complex visual hallucinations, the interaction between cognitive decline, visual impairment, and other visual symptoms remains poorly understood. Our aim was to characterize the spectrum of visual symptomatology in PD and examine clinical predictors for their occurrence. Sixty-four subjects with PD, 26 with PD dementia, and 32 age-matched controls were assessed for visual symptoms, cognitive impairment, and ocular pathology. Complex visual hallucinations were common in PD (17%) and PD dementia (89%). Dementia subjects reported illusions (65%) and presence (62%) more frequently than PD or control subjects, but the frequency of passage hallucinations in PD and PD dementia groups was equivalent (48% versus 69%, respectively; P = 0.102). Visual acuity and contrast sensitivity was impaired in parkinsonian subjects, with disease severity and age emerging as the key predictors. Regression analysis identified a variety of factors independently predictive of complex visual hallucinations (e.g., dementia, visual acuity, and depression), illusions (e.g., excessive daytime somnolence and disease severity), and presence (e.g., rapid eye movement sleep behavior disorder and excessive daytime somnolence). Our results demonstrate that different "hallucinatory" experiences in PD do not necessarily share common disease predictors and may, therefore, be driven by different pathophysiological mechanisms. If confirmed, such a finding will have important implications for future studies of visual symptoms and cognitive decline in PD and PD dementia.     

Mirtazapine improves visual hallucinations in Parkinson's disease: a case report

Psychotic symptoms often occur as a complication in Parkinson's disease patients, and a set of criteria for Parkinson's disease with psychosis (PDPsy) has been established. Among these criteria, hallucinations are one of the specific symptoms, with visual hallucinations being the most common. While atypical antipsychotic agents are often used for the treatment of PDPsy, adverse effects, including extrapyramidal symptoms, often hinder its continuation or tolerance. There have been some reports and reviews indicating that antidepressants may be effective for PDPsy and other forms of dementia with psychosis. In this report, we present a patient with PDPsy who was treated with one of the new‐generation antidepressants, mirtazapine. Mirtazapine improved the patient's refractory psychotic symptoms, especially her visual hallucinations, without worsening her motor symptoms.     

Visual hallucinations in dementia and Parkinson's disease: A qualitative exploration of patient and caregiver experiences

Objectives

Visual hallucinations (VHs) can occur in several clinical conditions, of which the dementias, broadly defined, and Parkinson's disease rank among the most common. There is limited research on the lived experience of hallucinations among affected individuals and therefore a lack of evidence‐based management strategies. This study used qualitative methods to explore the VH experience of individuals with dementia or Parkinson's disease and their informal caregivers.

Methods

In‐depth interviews were conducted with 10 individuals with VHs and dementia and 11 informal caregivers, and 11 individuals with VHs and Parkinson's disease and 9 informal caregivers. Interviews were analysed using an inductive thematic approach.

Results

Three themes emerged from the data: “Insight and distress,” “Caregiver approach: challenging v reassurance,” and “Normality and stigma.” Insight appeared to affect whether hallucinations were perceived as threatening and whether acceptance occurred over time. Emotional reactions and management strategies varied as insight changed with disease progression. Concerns around stigmatisation negatively influenced help‐seeking and acceptance of the hallucinations.

Conclusions

Degree of insight and cognitive ability appear fundamental to the lived experience of hallucinations. Irrespective of the clinical context, support in early stages should focus on raising awareness of VH, symptom disclosure, stigma reduction, and contact with others affected. In later stages, the focus shifts to informal caregiver needs and a flexible approach to reassuring those affected.     

Comprehensive morphometry of subcortical grey matter structures in early‐stage Parkinson's disease

Previous imaging studies that investigated morphometric group differences of subcortical regions outside the substantia nigra between non‐demented Parkinson's patients and controls either did not find any significant differences, or reported contradictory results. Here, we performed a comprehensive morphometric analysis of 20 cognitively normal, early‐stage PD patients and 19 matched control subjects. In addition to relatively standard analyses of whole‐brain grey matter volume and overall regional volumes, we examined subtle localized surface shape differences in striatal and limbic grey matter structures and tested their utility as a diagnostic marker. Voxel‐based morphometry and volumetric comparisons did not reveal significant group differences. Shape analysis, on the other hand, demonstrated significant between‐group shape differences for the right pallidum. Careful diffusion tractography analysis showed that the affected parts of the pallidum are connected subcortically with the subthalamic nucleus, the pedunculopontine nucleus, and the thalamus and cortically with the frontal lobe. Additionally, microstructural measurements along these pathways, but not along other pallidal connections, were significantly different between the two groups. Vertex‐wise linear discriminant analysis, however, revealed limited accuracy of pallidal shape for the discrimination between patients and controls. We conclude that localized disease‐related changes in the right pallidum in early Parkinson's disease, undetectable using standard voxel‐based morphometry or volumetry, are evident using sensitive shape analysis. However, the subtle nature of these changes makes it unlikely that shape analysis alone will be useful for early diagnosis. Hum Brain Mapp 35:1681–1690, 2014. © 2013 Wiley Periodicals, Inc.     

Cognitive correlates of visual hallucinations in non-demented Parkinson's disease patients

BackgroundVisual hallucinations (VH) in Parkinson's disease (PD) are associated with PD dementia and have been related to cognitive impairments in non-demented PD patients. Reports on the specific cognitive domains affected are conflicting. The aim of the present study was to investigate the presence of specific cognitive impairments in non-demented PD patients with VH, compared to those without VH.MethodsWe compared the clinical characteristics and neuropsychological test scores of 31 non-demented PD patients with VH with those of 31 PD patients without VH that were carefully matched for sex, age, disease duration and educational level. Several non-motor symptoms, including depression, anxiety and sleep disturbances, were also taken into account, as these may influence cognitive performance.ResultsThe PD with VH group performed significantly worse on the Trail Making Test part A (p = 0.01) and the Rey Auditory Verbal Learning Test, immediate recall (p = 0.01). In addition, PD patients with VH were more anxious, more depressed and reported more sleep disturbances. Verbal learning scores were not associated with levels of anxiety, depression or sleep disruption, whereas worse Trail Making Test A performance was associated with concomitant sleep disturbances.ConclusionsIn non-demented PD patients, the presence of VH is associated with a cognitive profile characterized by impairments in verbal learning and probably attention. Since these cognitive functions are believed to be non-dopaminergic mediated functions, the present results support the hypothesis that multiple neurotransmitter systems, other than dopamine, contribute to the pathophysiology of VH in PD.     

Abnormal visual activation in Parkinson's disease patients

Among nonmotor symptoms observed in Parkinson's disease (PD) dysfunction in the visual system, including hallucinations, has a significant impact in their quality of life. To further explore the visual system in PD patients we designed two fMRI experiments comparing 18 healthy volunteers with 16 PD patients without visual complaints in two visual fMRI paradigms: the flickering checkerboard task and a facial perception paradigm. PD patients displayed a decreased activity in the primary visual cortex (Broadmann area 17) bilaterally as compared to healthy volunteers during flickering checkerboard task and increased activity in fusiform gyrus (Broadmann area 37) during facial perception paradigm. Our findings confirm the notion that PD patients show significant changes in the visual cortex system even before the visual symptoms are clinically evident. Further studies are necessary to evaluate the contribution of these abnormalities to the development visual symptoms in PD. © 2010 Movement Disorders Society     

Subcortical grey matter changes in untreated,early stage Parkinson's disease without dementia

BackgroundPrevious MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage.MethodsWe recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively.ResultsVoxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity.ConclusionsOur results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients.     

Visual hallucinations, white matter lesions and disease severity in Parkinson's disease

OBJECTIVES: To determine if visual hallucinations in patients with Parkinson's disease are associated with an increased prevalence of white matter lesions. PATIENTS AND METHODS: Fifteen patients with (group 1) and 15 patients without (group 2) a history of visual hallucinations were studied. Both groups were matched for age. Magnetic resonance imaging was performed in all patients using standard T2 weighted Fast-Spin-Echo sequences. Assessment of cerebral white matter changes was performed using a modification of established criteria, with semiquantitative evaluation of periventricular and deep white matter changes. RESULTS: There was no significant group difference with regard to the total amount of white matter changes, nor was a group difference found between the amount or extent of periventricular hyperintensities or deep white matter lesions. Group 1 was significantly (P = 0.001) more disabled as evaluated by Hoehn/Yahr stage controlling for age and duration of disease. Mean increases in Hoehn/Yahr stage were not significantly greater in group 1 compared with group 2 at a 2-year follow-up examination (0.6 vs. 0.3, P = 0.166). CONCLUSION: Our data suggest that visual hallucinations are an indicator of a more aggressive course of the disease, but are not associated with a higher prevalence of global or occipital white matter lesions.     

Parkinson's disease,visual hallucinations and apomorphine: A review of the available evidence

BackgroundVisual hallucinations (VH) occur in the clinical course of Parkinson's disease (PD) and are predictive for PD dementia. The genesis of VH is related to impaired bottom-up and/or top-down visual processing which can be linked to cholinergic dysfunction and mono-amine imbalance. The risk of developing VH with oral dopamine agonists seems to increase with advancing disease, while in contrast some clinical studies suggest that apomorphine does not worsen VH, or might even improve VH.MethodsThe aim of this study is to review the current evidence of apomorphine and its effects on VH in PD patients.ResultsApomorphine is well-tolerated in PD patients with VH, also in long-term follow-up studies. Apomorphine is also suggested to have the potential to alleviate VH. Some data suggest that the positive effect of apomorphine on VH is related to its piperidine moiety, part of many anti-psychotics. Irrespective this piperidine moiety, apomorphine has a high D₁–like receptor affinity, and acts as a serotonin 5-HT_2A receptor antagonist, which might explain the potential anti-hallucinogenic properties as well.ConclusionThe anecdotal evidence suggesting that apomorphine has a relatively low proclivity to induce VH in PD may be due to its capacity to reduce serotonergic activity in particular. Therefore apomorphine is still an option to consider in fluctuating PD patients with VH, if they are treated properly with respect to their cholinergic deficits and existing VH.     

Coping strategies for visual hallucinations in Parkinson's disease.

We assessed the use of coping strategies in Parkinson's disease patients with visual hallucinations, using a semi-structured questionnaire. We found that 36 of our 46 Parkinson's disease subjects with hallucinations (78%) used coping strategies: cognitive techniques in 69%; interactive techniques in 62%; and visual techniques in 33%.     

Visual hallucinations and altered visual information processing in Parkinson disease and dementia with Lewy bodies

Visual hallucinations (VHs) are common in dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), while auditory hallucinations are rare. To neurophysiologically investigate the pathophysiology of VHs in these disorders, we studied event‐related potentials (ERPs) of DLB, PDD, and Alzheimer's disease (AD) patients. We compared visual and auditory ERP latencies among PDD patients with and without VHs (PDD‐H: 11, PDD‐N: 6), DLB patients (24), and AD patients (21). To elicit visual and auditory ERPs, a facial discrimination paradigm and a conventional auditory odd‐ball paradigm, respectively, were used. The mean visual P3 latencies in the PDD‐H and DLB groups were significantly longer than that in the AD group, while the mean auditory P3 latencies in all four patient groups were comparable. The mean visual P2 latencies in the PDD‐N, PDD‐H, and DLB groups were significantly longer than that in the control group. Our findings suggest that visual cognitive functions are selectively impaired in hallucinatory patients with DLB and PDD. VHs may be associated in part with predominant visual cognitive impairments attributable to PDD and DLB pathologies. Our findings also suggest that the impairments occur at the early stage of facial information processing. © 2010 Movement Disorder Society