Aarsland D, Bronnick K, Ehrt U, De Deyn PP, Tekin S, Emre M et al. Neuropsychiatric symptoms in patients with Parkinson's disease and dementia: frequency, profile and associated care giver stress. J Neurol Neurosurg Psychiatr 78: 36-42

Centre for Clinical Neuroscience Research, Stavanger University Hospital, Stavanger, Norway.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 02/2007; 78(1):36-42. DOI: 10.1136/jnnp.2005.083113
Source: PubMed


To explore the profile of neuropsychiatric symptoms in patients with dementia associated with Parkinson's disease (PDD).
537 patients with PDD drawn from an international multicentre clinical trial of rivastigmine were assessed using the 10-item Neuropsychiatric Inventory (NPI). A cluster analysis was used to investigate the inter-relationship of NPI items. Associations between the clusters and demographic and clinical variables were analysed.
89% of the patients presented at least one symptom on the NPI, 77% had two or more symptoms and 64% had at least one symptom with a score > or = 4. The most common symptoms were depression (58%), apathy (54%), anxiety (49%) and hallucinations (44%). Patients with more severe dementia and advanced Parkinson's disease had more neuropsychiatric symptoms. Nearly 60% of the care givers reported at least one NPI symptom to be of at least moderate severe distress. Five NPI clusters were identified: one group with few and mild symptoms (52%); a mood cluster (11%, high scores on depression, anxiety and apathy); apathy (24%; high apathy and low scores on other items); agitation (5%, high score on agitation and high total NPI score); and a psychosis cluster (8%; high scores on delusions and hallucinations). The psychosis and agitation clusters had the lowest Mini-Mental State Examination score and the highest Unified Parkinson's Disease Rating Scale and care giver distress scores.
Neuropsychiatric symptoms are common in patients with PDD. The profile of these symptoms differs from that in other types of dementia. Subgroups with different neuropsychiatric profiles were identified. These subgroups may be associated with distinct neurobiological changes, which should be explored in future studies.

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Available from: Kolbjorn Bronnick,
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    • "Parkinson's disease (PD) is a neurodegenerative disease that affects autonomic, cognitive, motor, and sensory brain regions (Braak et al. 2004). Therefore, non-motor symptoms such as dementia are also detected in patients with PD (Aarsland et al. 2007), but this has attracted much lesser attention. It is likely that these alterations in cognitive functions are associated with brain regions such as the hippocampus and cerebral cortex. "
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    ABSTRACT: It has been postulated that the accumulation of extracellular α-synuclein (α-syn) might alter the neuronal membrane by formation of "pore-like structures" that will lead to alterations in ionic homeostasis. However, this has never been demonstrated to occur in brain neuronal plasma membranes. In this study, we show that α-syn oligomers rapidly associate to hippocampal membranes in a punctate fashion, resulting in increased membrane conductance (5 fold over control) and the influx of both calcium and a fluorescent glucose analogue. The enhancement in intracellular calcium (1.7 fold over control) caused a large increase in the frequency of synaptic transmission (2.5 fold over control), calcium transients (3 fold over control) and synaptic vesicle release. Both primary hippocampal and dissociated nigral neurons showed rapid increases in membrane conductance by α-syn oligomers. In addition, we show here that α-syn caused synaptotoxic failure associated to a decrease in SV2, a membrane protein of synaptic vesicles associated to neurotransmitter release. In conclusion, extracellular α-syn oligomers facilitates the perforation of the neuronal plasma membrane, thus explaining, in part, the synaptotoxicity observed in neurodegenerative diseases characterized by its extracellular accumulation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 02/2015; 132(6). DOI:10.1111/jnc.13060 · 4.28 Impact Factor
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    • "VH in PD impact upon quality of life [Diederich et al., 2009], and predict cognitive deterioration and mortality [Aarsland et al., 2007; Fenelon et al., 2000]. However, the nature and extent of brain pathology underlying PDVH remains poorly understood. "
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    ABSTRACT: Background: Visual hallucinations (VH) are one of the most striking nonmotor symptoms in Parkinson's disease (PD), and predict dementia and mortality. Aberrant default mode network (DMN) is associated with other psychoses. Here, we tested the hypothesis that DMN dysfunction contributes to VH in PD. Methods: Resting state functional data was acquired from individuals with PD with VH (PDVH) and without VH (PDnonVH), matched for levodopa drug equivalent dose, and a healthy control group (HC). Independent component analysis was used to investigate group differences in functional connectivity within the DMN. In addition, we investigated whether the functional changes associated with hallucinations were accompanied by differences in cortical thickness. Results: There were no group differences in cortical thickness but functional coactivation within components of the DMN was significantly lower in both PDVH and PDnonVH groups compared to HC. Functional coactivation within the DMN was found to be greater in PDVH group relative to PDnonVH group. Conclusion: Our study demonstrates, for the first time that, within a functionally abnormal DMN in PD, relatively higher "connectivity" is associated with VH. We postulate that aberrant connectivity in a large scale network affects sensory information processing and perception, and contributes to "positive" symptom generation in PD.
    Human Brain Mapping 11/2014; 35(11). DOI:10.1002/hbm.22577 · 5.97 Impact Factor
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    • "For example, a longitudinal study of a PD cohort without dementia found that after a median period of 18 months, the proportion of those who converted to dementia was significantly higher in those with apathy (Dujardin et al., 2009). In PDD, apathy had been reported with a frequency of 23 to 24% (Aarsland et al., 2001a), although a more recent study analyzing a large sample of mild-moderate PDD patients reported a higher figure (54%) (Aarsland et al., 2007), compared to 17% in nondemented patients (Aarsland et al., 2001b). Dujardin et al. (2009) suggest Cipriani et al. "
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    ABSTRACT: Apathy, characterized by lack of motivation and loss of initiative, is a non-cognitive symptom that affects a high proportion, but not all, of patients with all forms of dementia. To explore the phenomenon of apathy in people with dementia, we searched the PubMed and Google Scholar electronic databases for original research and review articles on apathetic behaviors in patients with dementia using the search terms "apathy, behavioral and psychological symptoms, dementia, Alzheimer's disease, Frontotemporal dementia, Dementia associated with Parkinson's disease, Huntington's disease, Vascular dementia". Some nosological aspects, neurobiological basis, and assessment of, as well as, potential benefits of non-pharmacologic and pharmacologic interventions for apathy in dementia are discussed. Greater understanding of apathy will improve the identification, intervention, and treatment of this ubiquitous and pernicious syndrome.
    Journal of Nervous & Mental Disease 10/2014; 202(10):718-724. DOI:10.1097/NMD.0000000000000190 · 1.69 Impact Factor
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