Visual hallucinations in Alzheimer's disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies

PLOS ONE, Nov 2019

Visual hallucinations (VHs) are among the most striking features of dementia with Lewy bodies (DLB). Given that Lewy body pathology is frequently observed in the brains of patients with AD, we aimed to study factors associated with VHs in AD and examine their association with DLB features. This cross-sectional study enrolled a consecutive series of AD patients who visited the dementia clinic of a regional hospital. Clinically diagnosed possible or probable DLB cases were excluded. VH frequency and associated factors including age, sex, education, disease severity, DLB features, vascular risk factors, cognitive function, and neuropsychiatric symptoms were compared between AD patients with VHs (VH+) and those without VHs (VH−). Among a total of 295 patients analyzed, 42 (14.2%) had VHs. After adjusting for age, sex, and disease severity, DLB features including fluctuations in cognition scores, rapid-eye-movement behavioral disorder (RBD), and severe neuroleptic sensitivity were more frequent in the VH+ group. Furthermore, depression score, total Neuropsychiatric Inventory (NPI) score, and total caregiver burden score as assessed by the NPI were higher in the VH+ group. Among neuropsychiatric symptoms, delusions, hallucinations in the non-visual domains, anxiety, and disinhibition were more frequent in the VH+ group. Conversely, none of the vascular risk factors (VRFs) or cognitive domains of the Cognitive Abilities Screening Instrument (CASI) was associated with VHs in AD. In summary, VHs, albeit occurring at a low rate, had a high impact on AD. Diagnostic features of DLB, including fluctuations, RBD, and severe neuroleptic sensitivity were significantly associated with VHs in AD. AD patients with VHs tended to have more severe neuropsychiatric symptoms and greater caregiver burden.

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Visual hallucinations in Alzheimer's disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies

October Visual hallucinations in Alzheimer's disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies Pai-Yi Chiu 0 1 Min-Hsien Hsu 0 1 Chein-Wei Wang 1 Chun-Tang Tsai 1 Ming-Chyi Pai 1 0 Department of Neurology, Show Chwan Memorial Hospital , Changhua, Taiwan , 2 Department of Neurology, Lin-Shin Hospital , Taichung, Taiwan , 3 Department of Guidance and Counseling, National Changhua University of Education, Changhua, Taiwan, 4 Division of Behavioral Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University , Tainan , Taiwan , 5 Alzheimer's Disease Research Center, National Cheng Kung University Hospital , Tainan , Taiwan , 6 Institute of Gerontology, College of Medicine, National Cheng Kung University , Tainan , Taiwan 1 Editor: Mathias Toft , Oslo Universitetssykehus , NORWAY Visual hallucinations (VHs) are among the most striking features of dementia with Lewy bodies (DLB). Given that Lewy body pathology is frequently observed in the brains of patients with AD, we aimed to study factors associated with VHs in AD and examine their association with DLB features. This cross-sectional study enrolled a consecutive series of AD patients who visited the dementia clinic of a regional hospital. Clinically diagnosed possible or probable DLB cases were excluded. VH frequency and associated factors including age, sex, education, disease severity, DLB features, vascular risk factors, cognitive function, and neuropsychiatric symptoms were compared between AD patients with VHs (VH+) and those without VHs (VH−). Among a total of 295 patients analyzed, 42 (14.2%) had VHs. After adjusting for age, sex, and disease severity, DLB features including fluctuations in cognition scores, rapid-eye-movement behavioral disorder (RBD), and severe neuroleptic sensitivity were more frequent in the VH+ group. Furthermore, depression score, total Neuropsychiatric Inventory (NPI) score, and total caregiver burden score as assessed by the NPI were higher in the VH+ group. Among neuropsychiatric symptoms, delusions, hallucinations in the non-visual domains, anxiety, and disinhibition were more frequent in the VH+ group. Conversely, none of the vascular risk factors (VRFs) or cognitive domains of the Cognitive Abilities Screening Instrument (CASI) was associated with VHs in AD. In summary, VHs, albeit occurring at a low rate, had a high impact on AD. Diagnostic features of DLB, including fluctuations, RBD, and severe neuroleptic sensitivity were significantly associated with VHs in AD. AD patients with VHs tended to have more severe neuropsychiatric symptoms and greater caregiver burden. - Data Availability Statement: All relevant data are within the paper. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Introduction Alzheimer's disease (AD) is the most common type of dementia. Psychotic symptoms, including delusions and hallucinations, are striking features that cast a great impact on both patients with AD (PwAD) and their caregivers [ 1 ]. Among psychotic symptoms, delusions start in early stages of AD and are frequently comorbid throughout the course of dementia [ 2,3 ], whereas visual hallucinations (VHs), which are far less frequently observed in PwAD, manifest in later disease stages [2]. Distinct from AD, VHs are among the most important diagnostic features for dementia with Lewy bodies (DLB) [ 4,5 ]. VHs may start earlier in DLB and are observed significantly more frequently in DLB than in AD or other dementias [2,6±8]. Previous studies reveal that dementia patients with psychotic features are usually older and that disease onset occurs at a later age [ 9,10 ]. Additionally, dementia is usually more severe in patients with psychotic features [9±11]. Gender association with VH symptoms, in contrast, has been noted or studied less in previous studies [ 11,12 ]. Impaired visual acuity, perception, and/or visuospatial dysfunction are also associated with VHs in AD [ 12,13 ]. For example, the presence of VHs in PwAD was associated with increased occipital periventricular hyperintensities and an absence of occipital deep white matter hyperintensities on brain magnetic resonance imaging (MRI) [14]. Hallucinations in PwAD are significantly associated with depression, a relationship that is further mediated by inhibition [ 15 ]. Moreover, hallucinations are significantly more likely to occur in subjects with no APOE4 alleles than in those with two E4 alleles [ 16 ]. AD patients with VHs are also more likely to have Lewy body pathology than those without VHs [ 17 ]. Psychosis of AD leads to a faster functional impairment and increases the mortality risk [ 18 ]. The presence of hallucinations is selectively associated with more rapid cognitive decline in AD [19]. Furthermore, hallucinations are associated (...truncated)


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Pai-Yi Chiu, Min-Hsien Hsu, Chein-Wei Wang, Chun-Tang Tsai, Ming-Chyi Pai. Visual hallucinations in Alzheimer's disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies, PLOS ONE, 2017, Volume 12, Issue 10, DOI: 10.1371/journal.pone.0186886