Disease progression in dementia with Lewy bodies: A longitudinal study on clinical symptoms, quality of life and functional impairment.

BACKGROUND AND OBJECTIVES: Dementia with Lewy Bodies (DLB) is a heterogeneous disease, with variable signs and symptoms across multiple domains. We aimed to identify associations with rate of change in cognition, everyday functioning (IADL) and quality of life (QoL). METHODS: We included 121 DLB patients (69 ± 6 yrs, 14%F, MMSE: 25 ± 3) in our prospective cohort (follow-up 2 ± 1 yrs). We described progression of symptoms and cognitive decline over time. Mixed models were used to investigate whether changes in symptoms were associated to changes in IADL (FAQ), QoL (QoL-AD) and caregiver burden (ZBI). Last, we investigated whether baseline symptoms and biomarkers predicted decline in cognition (MMSE), IADL (FAQ) and QoL (QoL-AD). RESULTS: Parkinsonism and RBD were most frequently present early in the disease course, while hallucinations were more likely to develop in a later stage. MMSE (annual change ß ± SE = -2.06 ± 0.23), QoL-AD (-1.03 ± 0.20), and FAQ (3.04 ± 0.30) declined over time. Increasing severity of clinical symptoms was associated to increases in FAQ, QoL-AD and caregiver burden. Baseline clinical symptoms were not predictive for decline in these outcomes. By contrast, AD co-pathology (CSF pTau/Aß42 ratio) was associated to steeper decline in MMSE (-1.23 ± 0.54). Medial temporal atrophy (-0.81 ± 0.26) and global cortical atrophy (-0.73 ± 0.36) predisposed for decline in QoL-AD. CONCLUSIONS: Our findings imply that underlying disease processes, rather than clinical symptomatology aid in predicting decline. These findings are relevant for treatment strategies and the development of DLB specific outcome measures.

Prodromal Dementia With Lewy Bodies: Clinical Characterization and Predictors of Progression.

OBJECTIVE: The objective of this study was to examine clinical characteristics, cognitive decline, and predictors for time to dementia in prodromal dementia with Lewy bodies with mild cognitive impairment (MCI-LB) compared with prodromal Alzheimer's disease (MCI-AD). METHODS: We included 73 MCI-LB patients (12% female; 68 ± 6 years; Mini Mental State Examination, 27 ± 2) and 124 MCI-AD patients (48% female; 68 ± 7 years; Mini Mental State Examination, 27 ± 2) from the Amsterdam Dementia Cohort. Follow-up was available for 61 MCI-LB patients and all MCI-AD patients (3 ± 2 years). We evaluated dementia with Lewy bodies core features, neuropsychiatric symptoms, caregiver burden (Zarit caregiver burden interview), MRI, apolipoprotein genotype, and cerebrospinal fluid biomarkers (tau/Aß1-42 ratio). Longitudinal outcome measures included cognitive slopes (memory, attention, executive functions, and language and visuospatial functions) and time to dementia. RESULTS: Parkinsonism was the most frequently present core feature in MCI-LB (69%). MCI-LB patients more often had neuropsychiatric symptoms and scored higher on ZARIT when compared with the MCI-AD patients. Linear mixed models showed that at baseline, MCI-LB patients performed worse on nonmemory cognitive domains, whereas memory performance was worse in MCI-AD patients. Over time, MCI-LB patients declined faster on attention, whereas MCI-AD patients declined faster on the Mini Mental State Examination and memory. Cox proportional hazards regressions showed that in the MCI-LB patients, lower attention (hazard ratio [HR] = 1.6; 95% confidence interval [CI], 1.1-2.3) and more posterior cortical atrophy (HR = 3.0; 95% CI, 1.5-5.8) predicted shorter time to dementia. In the MCI-AD patients, worse performance on memory (HR = 1.1; 95% CI, 1.0-1.2) and executive functions (HR = 1.3; 95% CI, 1.0-1.6) were independently associated with time to Alzheimer's dementia. CONCLUSION: MCI-LB patients have distinct neuropsychiatric and cognitive profiles with prominent decline in attention when compared with MCI-AD patients. Our results highlight the importance of early diagnosis because symptoms already have an impact in the prodromal stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is a neurodegenerative disorder with a wide heterogeneity of symptoms, which suggests the existence of different subtypes. We used data-driven analysis of magnetic resonance imaging (MRI) data to investigate DLB subtypes. We included 165 DLB from the Mayo Clinic and 3 centers from the European DLB consortium and performed a hierarchical cluster analysis to identify subtypes based on gray matter (GM) volumes. To characterize the subtypes, we used demographic and clinical data, as well as ß-amyloid, tau, and cerebrovascular biomarkers at baseline, and cognitive decline over three years. We identified 3 subtypes: an older subtype with reduced cortical GM volumes, worse cognition, and faster cognitive decline (n = 49, 30%); a subtype with low GM volumes in fronto-occipital regions (n = 76, 46%); and a subtype of younger patients with the highest cortical GM volumes, proportionally lower GM volumes in basal ganglia and the highest frequency of cognitive fluctuations (n = 40, 24%). This study shows the existence of MRI subtypes in DLB, which may have implications for clinical workout, research, and therapeutic decisions.

Performance of a [18F]Flortaucipir PET Visual Read Method Across the Alzheimer Disease Continuum and in Dementia With Lewy Bodies.

BACKGROUND AND OBJECTIVES: Recently, the US Food and Drug Administration approved the tau-binding radiotracer [18F]flortaucipir and an accompanying visual read method to support the diagnostic process in cognitively impaired patients assessed for Alzheimer disease (AD). Studies evaluating this visual read method are limited. In this study, we evaluated the performance of the visual read method in participants along the AD continuum and dementia with Lewy bodies (DLB) by determining its reliability, accordance with semiquantitative analyses, and associations with clinically relevant variables. METHODS: We included participants who underwent tau-PET at Amsterdam University Medical Center. A subset underwent follow-up tau-PET. Two trained nuclear medicine physicians visually assessed all scans. Inter-reader agreement was calculated using Cohen κ. To examine the concordance of visual read tau positivity with semiquantification, we defined standardized uptake value ratio (SUVr) positivity using different threshold approaches. To evaluate the prognostic value of tau-PET visual read, we performed linear mixed models with longitudinal Mini-Mental State Examination (MMSE). RESULTS: We included 263 participants (mean age 68.5 years, 45.6% female), including 147 cognitively unimpaired (CU) participants, 97 amyloid-positive participants with mild cognitive impairment or AD dementia (AD), and 19 participants with DLB. The visual read inter-reader agreement was excellent (κ = 0.95, CI 0.91-0.99). None of the amyloid-negative CU participants (0/92 [0%]) and 1 amyloid-negative participant with DLB (1/12 [8.3%]) were tau-positive. Among amyloid-positive participants, 13 CU participants (13/52 [25.0%]), 85 with AD (85/97 [87.6%]), and 3 with DLB (3/7 [42.9%]) were tau-positive. Two-year follow-up visual read status was identical to baseline. Tau-PET visual read corresponded strongly to SUVr status, with up to 90.4% concordance. Visual read tau positivity was associated with a decline on the MMSE in CU participants (ß = -0.52, CI -0.74 to -0.30, p < 0.001) and participants with AD (ß = -0.30, CI -0.58 to -0.02, p = 0.04). DISCUSSION: The excellent inter-reader agreement, strong correspondence with SUVr, and longitudinal stability indicate that the visual read method is reliable and robust, supporting clinical application. Furthermore, visual read tau positivity was associated with prospective cognitive decline, highlighting its additional prognostic potential. Future studies in unselected cohorts are needed for a better generalizability to the clinical population. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that [18F]flortaucipir visual read accurately distinguishes patients with low tau-tracer binding from those with high tau-tracer binding and is associated with amyloid positivity and cognitive decline.

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

BACKGROUND AND OBJECTIVES: The ATN framework has been developed to categorize biological processes within the Alzheimer disease (AD) continuum. Because 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 with prognosis. METHODS: We included 202 patients with DLB from the Amsterdam Dementia Cohort (68±7 years; 19% female; Mini-Mental State Examination 24 ± 3; abnormal DAT-SPECT 105/119). Patients were classified into 8 profiles according to the ATN framework, using CSF ß-amyloid (Aß)42 (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±2 years for n = 139). Mortality risk was assessed using Cox proportional hazards analysis. Analyses were performed on the 8 profiles as well as 3 clustered categories (normal AD biomarkers, non-AD pathologic change, and AD continuum). RESULTS: Fifty (25%) patients with DLB 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 REM sleep behavior disorder symptoms. Parkinsonism was more often present in A+T- compared to A-T+ patients (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 patients with DLB aids in subtyping patients based on underlying biological processes and could provide targets for future treatment strategies (for example, AD-modifying treatment). Expanding the framework by incorporating markers for α-synucleinopathy would improve the use of the framework to characterize patients with dementia with mixed pathology, which could enhance proper stratification of patients for therapeutic trials.

Optimizing cCOG, a Web-based tool, to detect dementia with Lewy Bodies.

Introduction: Distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) is challenging due to overlapping presentations. We adapted a Web-based test tool, cCOG, by adding a visuospatial task and a brief clinical survey and assessed its ability to differentiate between DLB and AD. Methods: We included 110 patients (n = 30 DLB, n = 32 AD dementia, and n = 48 controls with subjective cognitive decline (SCD)). Full cCOG comprises six cognitive subtasks and a survey addressing self-reported DLB core and autonomic features. First, we compared cCOG cognitive tasks to traditional neuropsychological tasks for all diagnostic groups and clinical questions to validated assessments of clinical features in DLB only. Then, we studied the performance of cCOG cognitive tasks and clinical questions, separately and combined, in differentiating diagnostic groups. Results: cCOG cognitive tasks and clinical survey had moderate to strong correlations to standard neuropsychological testing (.61≤ r s ≤ .77) and to validated assessments of clinical features (.41≤ r s ≤ .65), except for fluctuations and REM-sleep behavior disorder (RBD) (r s = .32 and r s = .10). Full cCOG, including both cognitive tasks and brief survey had a diagnostic accuracy (acc) of 0.82 [95% CI 0.73-0.89], with good discrimination of DLB versus AD (acc 0.87 [0.76-0.95]) and DLB versus controls (acc 0.94 [0.86-0.98]). Conclusion: We illustrated that cCOG aids in distinguishing DLB and AD patients by using remote assessment of cognition and clinical features. Our findings pave the way to a funneled, harmonized diagnostic process among memory clinics and, eventually, a more timely and accurate diagnosis of DLB and AD.

Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data.

BACKGROUND: Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer's disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features. METHODS: We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions. RESULTS: We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-ß and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores. CONCLUSIONS: This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials.

Psychosocial Effects of COVID-19 Measures on (Pre-)Dementia Patients During Second Lockdown.

BACKGROUND: The COVID-19 pandemic poses enormous social challenges, especially during lockdown. People with cognitive decline and their caregivers are particularly at risk of lockdown consequences. OBJECTIVE: To investigate psychosocial effects in (pre-)dementia patients and caregivers during second lockdown and compare effects between first and second lockdown. METHODS: We included n = 511 (pre-)dementia patients and n = 826 caregivers from the Amsterdam Dementia Cohort and via Alzheimer Nederland. All respondents completed a self-designed survey on psychosocial effects of COVID-19. We examined relations between experienced support and psychosocial and behavioral symptoms using logistic regression. In a subset of patients and caregivers we compared responses between first and second lockdown using generalized estimating equation (GEE). RESULTS: The majority of patients (≥58%) and caregivers (≥60%) reported that family and friends, hobbies, and music helped them cope. Support from family and friends was strongly related to less negative feelings in patients (loneliness: OR = 0.3[0.1-0.6]) and caregivers (loneliness: OR = 0.2[0.1-0.3]; depression: OR = 0.4[0.2-0.5]; anxiety: OR = 0.4[0.3-0.6]; uncertainty: OR = 0.3[0.2-0.5]; fatigue: OR = 0.3[0.2-0.4]; stress: OR = 0.3[0.2-0.5]). In second lockdown, less psychosocial and behavioral symptoms were reported compared to first lockdown (patients; e.g., anxiety: 22% versus 13%, p = 0.007; apathy: 27% versus 8%, p < 0.001, caregivers; e.g., anxiety: 23% versus 16%, p = 0.033; patient's behavioral problems: 50% versus 35%, p < 0.001). Patients experienced more support (e.g., family and friends: 52% versus 93%, p < 0.001; neighbors: 28% versus 66%, p < 0.001). CONCLUSION: During second lockdown, patients and caregivers adapted to challenges posed by lockdown, as psychosocial and behavioral effects decreased, while patients experienced more social support compared to first lockdown. Support from family and friends is a major protective factor for negative outcomes in patients and caregivers.

Diagnostic Value of the CSF α-Synuclein Real-Time Quaking-Induced Conversion Assay at the Prodromal MCI Stage of Dementia With Lewy Bodies.

OBJECTIVE: To investigate whether the CSF α-synuclein (α-syn) real-time quaking-induced conversion (RT-QuIC) assay accurately identifies patients with mild cognitive impairment (MCI) due to probable Lewy body (LB) disease. METHODS: We applied α-syn RT-QuIC to 289 CSF samples obtained from 2 independent cohorts, including 81 patients with probable MCI-LB (age 70.7 ± 6.6 years, 13.6% female, Mini-Mental State Examination [MMSE] score 26.1 ± 2.4), 120 with probable MCI due to Alzheimer disease (AD) (age 68.6 ± 7.4 years, 45.8% female, MMSE score 25.5 ± 2.8), and 30 with unspecified MCI (age 65.4 ± 9.3 years, 30.0% female, MMSE score 27.0 ± 3.0). Fifty-eight individuals with no cognitive decline or evidence of neurodegenerative disease and 121 individuals lacking brain α-syn deposits at the neuropathologic examination were used as controls. RESULTS: RT-QuIC identified patients with MCI-LB against cognitively unimpaired controls with 95% sensitivity, 97% specificity, and 96% accuracy and showed 98% specificity in neuropathologic controls. The accuracy of the test for MCI-LB was consistent between the 2 cohorts (97.3% vs 93.7%). Thirteen percent of patients with MCI-AD also had a positive test; of note, 44% of them developed 1 core or supportive clinical feature of dementia with Lewy bodies (DLB) at follow-up, suggesting an underlying LB copathology. CONCLUSIONS: These findings indicate that CSF α-syn RT-QuIC is a robust biomarker for prodromal DLB. Further studies are needed to fully explore the added value of the assay to the current research criteria for MCI-LB. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CSF α-syn RT-QuIC accurately identifies patients with MCI-LB.

Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodies.

BACKGROUND: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity. OBJECTIVE: We tested if genetic variants in part explain the heterogeneity in DLB. METHODS: We tested the effects of variants previously associated with DLB (near APOE, GBA, and SNCA) and polygenic risk scores for Alzheimer's disease (AD-PRS) and Parkinson's disease (PD-PRS). We studied 190 probable DLB patients from the Alzheimer's dementia cohort and compared them to 2,552 control subjects. The p-tau/Aß1-42 ratio in cerebrospinal fluid was used as in vivo proxy to separate DLB cases into DLB with concomitant AD pathology (DLB-AD) or DLB without AD (DLB-pure). We studied the clinical measures age, Mini-Mental State Examination (MMSE), and the presence of core symptoms at diagnosis and disease duration. RESULTS: We found that all studied genetic factors significantly associated with DLB risk (all-DLB). Second, we stratified the DLB patients by the presence of concomitant AD pathology and found that APOE ɛ4 and the AD-PRS associated specifically with DLB-AD, but less with DLB-pure. In addition, the GBA p.E365K variant showed strong associated with DLB-pure and less with DLB-AD. Last, we studied the clinical measures and found that APOE ɛ4 associated with reduced MMSE, higher odds to have fluctuations and a shorter disease duration. In addition, the GBA p.E365K variant reduced the age at onset by 5.7 years, but the other variants and the PRS did not associate with clinical features. CONCLUSION: These finding increase our understanding of the pathological and clinical heterogeneity in DLB.

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies.

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

The Value of Neuropsychological Assessment in the Differentiation Between Behavioral Variant Frontotemporal Dementia and Late-Onset Psychiatric Disorders.

OBJECTIVE: To investigate which neuropsychological tests can discriminate between behavioral variant frontotemporal dementia (bvFTD) and psychiatric disorders presenting with similar late-onset frontal behavioral changes, such as apathy, disinhibition, reduced empathy, or compulsive behavior. METHODS: Patients presenting with frontal behavioral changes in middle or late adulthood received extensive baseline examinations, including neuropsychological assessment and brain imaging. After 2 years, examinations were repeated and patients were diagnosed according to DSM-IV or international bvFTD consensus criteria. The study period was April 2011-June 2015. Two groups were selected: 32 patients with bvFTD and 53 patients with a psychiatric or psychological diagnosis. Associations between neuropsychological test scores and diagnostic group were investigated with logistic regression analyses, and diagnostic accuracy was investigated with a receiver operating characteristic curve. RESULTS: BvFTD patients scored lower on tests for confrontational naming, gestalt completion, and verbal abstraction compared to psychiatric patients (P < .01). The confrontational naming test (Boston Naming Test) showed the strongest association with diagnostic group: a lower score indicated a higher probability for a bvFTD diagnosis (P < .001). This test could discriminate between the groups with good diagnostic accuracy (area under the curve = 0.81). Tests for attention, memory, and executive functions showed no discriminative ability between the groups. CONCLUSIONS: Although one of the criteria of bvFTD is low performance on executive tests, these tests are not useful in differentiating bvFTD from psychiatric disorders. We recommend administering language tests, especially an extensive confrontational naming test, to aid differentiation between bvFTD and a psychiatric disorder in patients presenting with late-onset frontal behavioral changes.

Diagnostic and prognostic value of EEG in prodromal dementia with Lewy bodies.

OBJECTIVE: Early biomarkers for dementia with Lewy bodies (DLB) are lacking. To determine whether EEG differentiates the prodromal phase of DLB from other causes of mild cognitive impairment (MCI) and whether EEG is predictive for time to conversion from MCI to DLB, we compared EEGs and clinical follow-up of patients with MCI due to DLB with those of patients with MCI due to Alzheimer disease (MCI-AD). METHODS: We compared 37 patients with MCI who developed DLB during follow-up or had an abnormal 123I-PF-CIT SPECT scan (MCI-DLB) with 67 age-matched patients with MCI-AD. EEGs were assessed visually with a score of increasing abnormality (range 1-5). We performed fast Fourier transform to analyze the power spectrum. With survival analyses, EEG characteristics were related to time to progression to dementia. RESULTS: The visual EEG score was higher in MCI-DLB (score >2 in 60%) compared to MCI-AD (score >2 in 8%, p < 0.001). We found frontal intermittent delta activity in 22% of MCI-DLB, not in MCI-AD. Patients with MCI-DLB had a lower peak frequency (7.5 [6.0-9.9] Hz vs 8.8 [6.8-10.2] in MCI-AD, p < 0.001) and more slow-wave activity. Several individual EEG measures showed good performance to discriminate MCI-DLB from MCI-AD (areas under the curve up to 0.94). In MCI-DLB, high visual EEG score, diffuse abnormalities, and low α2 power were related to time to progression to dementia (hazard ratios 4.1, 9.9, 5.1, respectively). CONCLUSIONS: Profound EEG abnormalities are already present in the prodromal stage of DLB and have diagnostic and prognostic value. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that EEG abnormalities are more common in MCI-DLB than MCI-AD.

Family History is Associated with Phenotype in Dementia with Lewy Bodies.

It is currently unknown whether patients with dementia with Lewy bodies (DLB) with relatives with dementia or Parkinson's disease (familial DLB patients) have a different phenotype than sporadic DLB patients. In this study, we aimed to examine disease onset, rate of cognitive decline, survival, and Alzheimer's disease (AD) biomarkers in patients with familial DLB (n = 154) and sporadic DLB (n = 137), using linear mixed model analysis and Cox regression analysis, among others. Familial patients had a shorter survival (8.0 years) and more often elevated cerebrospinal fluid AD biomarkers (47%) than sporadic patients (9.0 years; p≤0.001; 30%, p = 0.037). Our findings suggest that genetic factors are important in DLB and that the identification of new genetic factors will probably improve the prediction of prognosis.

Psychosocial Effects of Corona Measures on Patients With Dementia, Mild Cognitive Impairment and Subjective Cognitive Decline.

Background: The recent COVID-19 pandemic is not only a major healthcare problem in itself, but also poses enormous social challenges. Though nursing homes increasingly receive attention, the majority of people with cognitive decline and dementia live at home. We aimed to explore the psychosocial effects of corona measures in memory clinic (pre-)dementia patients and their caregivers. Methods: Between April 28th and July 13th 2020, n = 389 patients of Alzheimer center Amsterdam [n = 121 symptomatic (age = 69 ± 6, 33%F, MMSE = 23 ± 5), n = 268 cognitively normal (age = 66 ± 8, 40% F, MMSE = 29 ± 1)] completed a survey on psychosocial effects of the corona measures. Questions related to social isolation, worries for faster cognitive decline, behavioral problems and discontinuation of care. In addition, n = 147 caregivers of symptomatic patients completed a similar survey with additional questions on caregiver burden. Results: Social isolation was experienced by n = 42 (35%) symptomatic and n = 67 (25%) cognitively normal patients and two third of patients [n = 129 (66%); n = 58 (75%) symptomatic, n = 71 (61%) cognitively normal] reported that care was discontinued. Worries for faster cognitive decline were existed in symptomatic patients [n = 44 (44%)] and caregivers [n = 73 (53%)], but were also reported by a subgroup of cognitively normal patients [n = 27 (14%)]. Both patients [n = 56 (46%) symptomatic, n = 102 (38%) cognitively normal] and caregivers [n = 72 (48%)] reported an increase in psychological symptoms. More than three quarter of caregivers [n = 111(76%)] reported an increase in patients' behavioral problems. A higher caregiver burden was experienced by n = 69 (56%) of caregivers and n = 43 (29%) of them reported that a need for more support. Discontinuation of care (OR = 3.3 [1.3-7.9]), psychological (OR = 4.0 [1.6-9.9]) and behavioral problems (OR = 3.0 [1.0-9.0]) strongly related to experiencing a higher caregiver burden. Lastly, social isolation (OR = 3.2 [1.2-8.1]) and psychological symptoms (OR = 8.1 [2.8-23.7]) were red flags for worries for faster cognitive decline. Conclusion: Not only symptomatic patients, but also cognitively normal patients express worries for faster cognitive decline and psychological symptoms. Moreover, we identified patients who are at risk of adverse outcomes of the corona measures, i.e., discontinued care, social isolation, psychological and behavioral problems. This underlines the need for health care professionals to provide ways to warrant the continuation of care and support (informal) networks surrounding patients and caregivers to mitigate the higher risk of negative psychosocial effects.

Trajectories and Determinants of Quality of Life in Dementia with Lewy Bodies and Alzheimer's Disease.

BACKGROUND: Quality of Life (QoL) is an important outcome measure in dementia, particularly in the context of interventions. Research investigating longitudinal QoL in dementia with Lewy bodies (DLB) is currently lacking. OBJECTIVE: To investigate determinants and trajectories of QoL in DLB compared to Alzheimer's disease (AD) and controls. METHODS: QoL was assessed annually in 138 individuals, using the EQ5D-utility-score (0-100) and the health-related Visual Analogue Scale (VAS, 0-100). Twenty-nine DLB patients (age 69±6), 68 AD patients (age 70±6), and 41 controls (age 70±5) were selected from the Dutch Parelsnoer Institute-Neurodegenerative diseases and Amsterdam Dementia Cohort. We examined clinical work-up over time as determinants of QoL, including cognitive tests, neuropsychiatric inventory, Geriatric Depression Scale (GDS), and disability assessment of dementia (DAD). RESULTS: Mixed models showed lower baseline VAS-scores in DLB compared to AD and controls (AD: ß±SE = -7.6±2.8, controls: ß±SE = -7.9±3.0, p < 0.05). An interaction between diagnosis and time since diagnosis indicated steeper decline on VAS-scores for AD patients compared to DLB patients (ß±SE = 2.9±1.5, p < 0.1). EQ5D-utility-scores over time did not differ between groups. Higher GDS and lower DAD-scores were independently associated with lower QoL in dementia patients (GDS: VAS ß±SE = -1.8±0.3, EQ5D-utility ß±SE = -3.7±0.4; DAD: VAS = 0.1±0.0, EQ5D-utility ß±SE = 0.1±0.1, p < 0.05). No associations between cognitive tests and QoL remained in the multivariate model. CONCLUSION: QoL is lower in DLB, while in AD QoL shows steeper decline as the disease advances. Our results indicate that non-cognitive symptoms, more than cognitive symptoms, are highly relevant as they impact QoL.