Cognitive correlates and baseline predictors of future development of visual hallucinations in dementia with Lewy bodies

Pezzoli, Stefania; Cagnin, Annachiara; Bussè, Cinzia; Zorzi, Giovanni; Fragiacomo, Federica; Bandmann, Oliver; Venneri, Annalena

doi:10.1016/j.cortex.2021.05.018

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…6 Possibly there is a relation between presence of visual hallucinations and the severity of memory impairment, which is often more pronounced in patients with A+. 28 RBD was least frequently present in patients with the A+T+N+ profile. In accordance with our findings, 2 previous studies in autopsy-confirmed DLB also found more severe AD-related pathology in RBD-negative patients.…”

Section: Discussionmentioning

confidence: 93%

Association of the ATN Research Framework With Clinical Profile, Cognitive Decline, and Mortality in Patients With Dementia With Lewy Bodies

et al. 2022

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Background and Objectives:The ATN framework has been developed to categorize biological processes within the Alzheimer’s disease (AD) continuum. Since AD pathology often coincides with dementia with Lewy Bodies (DLB), we aimed to investigate the distribution of ATN profiles in DLB and associate ATN-profiles in DLB to prognosis.Methods:We included 202 DLB patients from the Amsterdam Dementia Cohort (68±7yrs, 19%F, MMSE: 24±3, DAT-SPECT abnormal: 105/119). Patients were classified into eight profiles according to the ATN framework, using CSF Aβ42 (A), CSF p-tau (T) and medial temporal atrophy scores (N). We compared presence of clinical symptoms in ATN profiles and used linear mixed models to analyze decline on cognitive tests (follow-up 3±2yrs for n=139). Mortality risk was assessed using Cox proportional hazards analysis. Analyses were performed on both the eight profiles, as well as three clustered categories (normal AD biomarkers, non-AD pathologic change, AD continuum).Results:Fifty (25%) DLB patients had normal AD biomarkers (A-T-N-), 37 (18%) had non-AD pathologic change (A-T+N-: 10%/A-T-N+: 6%/A-T+N+: 3%) and 115 (57%) were classified within the AD continuum (A+T-N-: 20%/A+T+N-: 16%/A+T-N+: 10%/A+T+N+: 9%). A+T+N+ patients were older and least often had RBD symptoms. Parkinsonism was more often present in A+T-, compared to A-T+ (independent of N). Compared to patients with normal AD biomarkers, patients in A+ categories showed steeper decline on memory tests and higher mortality risk. Cognitive decline and mortality did not differ between non-AD pathologic change and normal AD biomarkers.Discussion:In our DLB cohort, we found clinically relevant associations between ATN categories and disease manifestation. Patients within the AD continuum had steeper cognitive decline and shorter survival. Implementing the ATN framework within DLB patients aids in subtyping patients based on underlying biological processes and could provide targets for future treatment strategies, e.g. AD modifying treatment. Expanding the framework by incorporating markers for alpha-synucleinopathy would improve the use of the framework to characterize dementia patients with mixed pathology, which could enhance proper stratification of patients for therapeutic trials.

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Section: Discussionmentioning

confidence: 93%

Association of the ATN Research Framework With Clinical Profile, Cognitive Decline, and Mortality in Patients With Dementia With Lewy Bodies

et al. 2022

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“…Interestingly, non-hallucinating patients performed similarly to CN controls on the CDT -copy, suggesting that a combination of more severe visuoconstructive and visuospatial attention impairments may be associated with the clinical manifestation of VH. Lower scores on the Rey figure copy, assessing visuoconstructive abilities, have been detected previously in association with VH in hallucinating Parkinson's disease (PD) and DLB patients [38][39][40][41], and other studies identified visual perception impairments in patients with VH in PD and DLB [42][43][44].…”

Section: Discussionmentioning

confidence: 60%

A Multimodal Neuroimaging and Neuropsychological Study of Visual Hallucinations in Alzheimer’s Disease

Pezzoli

Manca

Cagnin

et al. 2022

JAD

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Background: Hallucinations in Alzheimer’s disease (AD) have been linked to more severe cognitive and functional decline. However, research on visual hallucinations (VH), the most common type of hallucinations in AD, is limited. Objective: To investigate the cognitive and cerebral macrostructural and metabolic features associated with VH in AD. Methods: Twenty-four AD patients with VH, 24 with no VH (NVH), and 24 cognitively normal (CN) matched controls were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Differences in regional gray matter (GM) volumes and cognitive performance were investigated with whole brain voxel-based morphometry analyses of MRI structural brain scans, and analyses of neuropsychological tests. Glucose metabolic changes were explored in a subsample of patients who had FDG-PET scans available. Results: More severe visuoconstructive and attentional deficits were found in AD VH compared with NVH. GM atrophy and hypometabolism were detected in occipital and temporal areas in VH patients in comparison with CN. On the other hand, NVH patients had atrophy and hypometabolism mainly in temporal areas. No differences in GM volume and glucose metabolism were found in the direct comparison between AD VH and NVH. Conclusion: In addition to the pattern of brain abnormalities typical of AD, occipital alterations were observed in patients with VH compared with CN. More severe visuoconstructive and attentional deficits were found in AD VH when directly compared with NVH, and might contribute to the emergence of VH in AD.

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“…For example, clock drawing was related to performance on the 45 and 90 conditions of the MR, which probably reflects the fact that patients would rely on internally visualizing the stimulus before successfully drawing a clock or comparing the shapes presented in the MR task. 42 Working memory, as measured with backward digit span, also correlated with accuracy on the MR task. This is in line with previous research supporting the role of executive function in the manipulation of internally visualized stimuli.…”

Section: Discussionmentioning

confidence: 95%

“…As predicted MR performance in DLB was correlated with measures of visuospatial ability and executive function. For example, clock drawing was related to performance on the 45 and 90° conditions of the MR, which probably reflects the fact that patients would rely on internally visualizing the stimulus before successfully drawing a clock or comparing the shapes presented in the MR task 42 . Working memory, as measured with backward digit span, also correlated with accuracy on the MR task.…”

Section: Discussionmentioning

confidence: 98%

An Adaptive Measure of Visuospatial Impairment in Dementia with Lewy Bodies

Phillips

Matar

Martens

et al. 2022

Movement Disord Clin Pract

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BackgroundBackground: Dementia with Lewy bodies (DLB) is a common cause of dementia with poor prognosis and high hospitalization rates. DLB is frequently misdiagnosed, with clinical features that overlap significantly with other diseases including Parkinson's disease (PD). Clinical instruments that discriminate and track the progression of cognitive impairment in DLB are needed. Objectives Objectives: The current study was designed to assess the utility of a mental rotation (MR) task for assessing visuospatial impairments in early DLB. Methods Methods: Accuracy of 22 DLB patients, 22 PD patients and 22 age-matched healthy controls in the MR task were compared at comparing shapes with 0 , 45 and 90 rotations. ResultsResults: Healthy controls and PD patients performed at similar levels while the DLB group were significantly impaired. Further, impairment in the visuospatial and executive function measures correlated with MR poor outcomes. Conclusion Conclusion:These findings support the MR task as an objective measure of visuospatial impairment with the ability to adjust difficulty to suit impairments in a DLB population. This would be a useful tool within clinical trials.

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Cognitive correlates and baseline predictors of future development of visual hallucinations in dementia with Lewy bodies

Cited by 7 publications

References 43 publications

Association of the ATN Research Framework With Clinical Profile, Cognitive Decline, and Mortality in Patients With Dementia With Lewy Bodies

Association of the ATN Research Framework With Clinical Profile, Cognitive Decline, and Mortality in Patients With Dementia With Lewy Bodies

A Multimodal Neuroimaging and Neuropsychological Study of Visual Hallucinations in Alzheimer’s Disease

An Adaptive Measure of Visuospatial Impairment in Dementia with Lewy Bodies

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