The Cognitive Profile of Mild Cognitive Impairment Due to Dementia With Lewy Bodies—An Updated Review

Objective: Dementia with Lewy Bodies (DLB) is the second most common type of neurodegenerative dementia. Yet, the domain-specific cognitive impairment of the mild cognitive impairment (MCI) phase of this disease (DLB-MCI) is still not been established. This article gives an updated review on the neuropsychological profile of DLB-MCI, building on the findings from a previous review. Methods: We performed systematic review and searched five different electronic databases (Scopus, Cochrane, EMBASE, MEDLINE, and PsycINFO) in May 2020 based on a PICO scheme. Our search was then restricted to articles published in 2019 and 2020. Ending up with a total of 90 articles to be reviewed by abstract and/or full text. Results: In total four papers were included, whereof only one met our full inclusion criteria. Despite a substantial heterogeneity, our findings indicate that DLB-MCI patients have a pattern of executive, visuospatial, and attentional deficits. Conclusion: The findings indicate that the neuropsychological profile of DLB-MCI is characterized by executive, visuospatial, and attentional deficits. Furthermore, the shortage of studies clearly underlines the paucity of published research into DLB-MCI and emphasizes the need for well-controlled studies.publishedVersio

A Longitudinal Study of Neurocognition in Dementia with Lewy Bodies Compared to Alzheimer`s Disease

Introduction: There are relatively few longitudinal studies on the differences in cognitive decline between Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), and the majority of existing studies have suboptimal designs. Aim: We investigated the differences in cognitive decline in AD compared to DLB over 4 years and cognitive domain predictors of progression. Methods: In a longitudinal study, 266 patients with first-time diagnosis of mild dementia were included and followed annually. The patients were tested annually with neuropsychological tests and screening instruments [MMSE (Mini-Mental Status Examination), Clinical Dementia Rating (CDR), the second edition of California Verbal Learning Test (CVLT-II), Trail Making Test A & B (TMT A & B), Stroop test, Controlled Oral Word Associations Test (COWAT) animal naming, Boston Naming Test, Visual Object and Space Perception Battery (VOSP) Cubes and Silhouettes]. Longitudinal analyses were performed with linear mixed effects (LME) models and Cox regression. Both specific neuropsychological tests and cognitive domains were analyzed. Results: This study sample comprised 119 AD and 67 DLB patients. In TMT A, the DLB patients had a faster decline over 4 years than patients with AD (p = 0.013). No other longitudinal differences in specific neuropsychological tests were found. Higher executive domain scores at baseline were associated with a longer time to reach severe dementia (CDR = 3) or death for the total sample (p = 0.032). High or low visuospatial function at baseline was not found to be associated with cognitive decline (MMSE) or progression of dementia severity (CDR) over time. Conclusion: Over 4 years, patients with DLB had a faster decline in TMT A than patients with AD, but this should be interpreted cautiously. Beyond this, there was little support for faster decline in DLB patients neuropsychologically than in AD patients.publishedVersio

Demens med Lewylegemer: søvn, kognisjon og nevropatologi

Background Sleep disorders are frequent in patients with dementia. Sleep disturbances can negatively influence the disease burden of dementia and accelerate the rate of cognitive decline. It is hypothesized that sleep pathology, such as REM sleep behavior disorder (RBD), can occur many years before symptomatic disease and that it can be one of the early manifestation of neurodegeneration in alpha-synucleinopathies, such as dementia with Lewy bodies (DLB). DLB is the third most frequent type of dementia, after Alzheimer’s dementia (AD) and vascular dementia (VaD). However, there are few validation studies of the DLB consensus criteria from 2005, and the criteria appear to still have low sensitivity. Objectives The main goals of this thesis were: 1) to investigate the frequency of sleep disturbances in dementia and compare sleep disturbance profiles in a group of patients with AD and DLB; 2) to assess the potential influence of probable RBD (pRBD) on the rate of dementia progression; and 3) to compare neuropathological diagnoses with clinical diagnoses based on DLB consensus criteria from 2005. In the first publication, we investigated the prevalence of different sleep disturbances (SD) in mild AD and mild DLB dementia, in order to characterize the profile of sleep disorders in these two dementias. We studied the relationship between SD, RBD, and neuropsychological symptoms to find out if they could be associated with a higher incidence of psychopathological symptoms, i.e. depression, anxiety, hallucinations. In the second publication, we tested the hypothesis that RBD could be a factor for a more aggressive dementia course in light of previous reports that idiopathic RBD (iRBD) is a risk factor for mild cognitive impairment (MCI) and dementia. RBD seems also to worsen the course of Parkinson’s disease (PD) and accelerate conversion from MCI to Parkinson’s disease dementia (PDD). We examined the association of pRBD with global cognitive decline and decline in the cognitive subdomains in a 4-years longitudinal study. In the third publication, we analyzed reliability between clinical and neuropathological diagnoses in the selection of 56 autopsied patients to characterize sensitivity and specificity of consensus criteria from 2005. Moreover, we discussed potential reasons for misdiagnosis. Subjects and methods The thesis was based on data from the prospective DEMVEST study which started in 2005 and was conducted until 2013. Patients with dementia and their caregivers were recruited from clinics of old age psychiatry and geriatrics in Western Norway. The inclusion criterion was mild dementia with Mini-Mental State Examination (MMSE) ≥20. Dementia diagnoses were made according to established criteria, and pathologically confirmed in a subsample of 56 cases. Patients with acute cognitive disturbances and known chronic psychiatric illness were excluded. MMSE was used for cognitive screening. A battery of neuropsychological tests was used for measuring cognition: Stroop test, Controlled Oral Word Associations Test, semantic fluency (COWAT), Boston Naming Test 15 items (BNT), Trail Making Test A and B (TMT A, TMT B), the California Verbal Learning Test-II (CVLT-II), Silhouettes and Cubes on the Visual Object and Space Perception Battery (VOSP). Standard statistical analyses were performed for demographical and clinical comparisons. Longitudinal analyses were conducted with generalized linear mixed models (GLMM). Results A total of 266 patients were included in the DEMVEST study, and our cohort consisted of 139 with AD, 82 with DLB, 17 with PDD, 13 with VaD and 5 with FTD, six with other diagnoses (normal ageing, mixed AD and VaD, alcoholic dementia, unspecified dementia). Numbers of participants varied in the three papers according to purposes of the studies. Paper 1: 56% of patients with dementia, represented by AD and DLB, had at least one sleep disorder, with predominance of insomni (34.8%). Sleep problems were significantly more frequent in the group of patients with DLB than with AD (73.2% vs. 45.7%, p<0,001). DLB diagnoses also increased the risk of having three or more sleep disorders. Having at least one sleep-related problem was associated with significantly higher rates of psychopathological symptoms compared to patients without any sleep disorders. The second most common sleep problem in the DLB group after insomni was pRBD, which was present in 40% of patients. Paper 2: Of the total 246 patients included at baseline we identified 47 (19.1%) with pRBD. Patients with pRBD had the same progression rate of dementia as patients without RBD, both in global cognition measured by MMSE and in different cognitive domains, during 4 years of follow-up. However, the results showed that patients with RBD had significantly lower performance in figure copying in MMSE, VOSP Cube, TMT A and Stroop Words compared to RBD-negative patients throughout the observation period. Paper 3: In a cohort of 56 patients who came to autopsy we found 31 cases with neuropathologically verified AD, 20 with DLB and PDD and five with other diagnoses. Results showed that for overall DLB/ PDD diagnosis there was a relative good consistency between the clinical and pathological diagnoses, with a sensitivity (SN) and specificity (SP) of 80% and 92% and that the positive predictive value (PPV) and negative predictive value (NPV) were 84% and 89% respectively. For possible and probable DLB alone (without PDD), the values of 73% (SN), 93% (SP), 79% (PPV) and 90% (NPV) were found. Of the 56 patients, seven were misdiagnosed; three patients with false positive DLB diagnosis and four with false negative DLB diagnosis. For AD diagnosis SN, SP, as well as PPV and NPV were 81%, 88%, 89% and 79%, respectively. We also discussed factors that could affect the accuracy of clinical diagnosis. Conclusions Sleep disturbances are common in dementia, but patients with DLB have more sleep problems and a more complicated pattern of sleep pathology than those with AD. Occurrence of at least one sleep disturbance seems to be related to a more severe course of psychiatric symptoms. We could not demonstrate that pRBD is a risk factor for faster progression of global cognition and cognition in various cognitive domains of dementia. Sensitivity, specificity and accuracy of clinical diagnoses were similar to results from previous studies which applied DLB consensus criteria from 2005 and showed that there is still a need to improve sensitivity

The Cognitive Profile of Mild Cognitive Impairment Due to Dementia With Lewy Bodies—An Updated Review

Objective: Dementia with Lewy Bodies (DLB) is the second most common type of neurodegenerative dementia. Yet, the domain-specific cognitive impairment of the mild cognitive impairment (MCI) phase of this disease (DLB-MCI) is still not been established. This article gives an updated review on the neuropsychological profile of DLB-MCI, building on the findings from a previous review. Methods: We performed systematic review and searched five different electronic databases (Scopus, Cochrane, EMBASE, MEDLINE, and PsycINFO) in May 2020 based on a PICO scheme. Our search was then restricted to articles published in 2019 and 2020. Ending up with a total of 90 articles to be reviewed by abstract and/or full text. Results: In total four papers were included, whereof only one met our full inclusion criteria. Despite a substantial heterogeneity, our findings indicate that DLB-MCI patients have a pattern of executive, visuospatial, and attentional deficits. Conclusion: The findings indicate that the neuropsychological profile of DLB-MCI is characterized by executive, visuospatial, and attentional deficits. Furthermore, the shortage of studies clearly underlines the paucity of published research into DLB-MCI and emphasizes the need for well-controlled studies

REM sleep behavior disorder is not associated with a more rapid cognitive decline in mild dementia

Objectives: REM sleep behavior disorder (RBD) is associated with cognitive dysfunctions and is a risk factor for development of mild cognitive impairment and dementia. However, it is unknown whether RBD is associated with faster cognitive decline in already established dementia. The main goal of this study was to determine if patients with mild dementia with and without RBD differ in progression rate and in specific neuropsychological measures over 4-year follow-up. Methods: This longitudinal, prospective study based on data from the DemVest study compares neuropsychological measures in a mild dementia cohort. A diagnosis of probable RBD (pRBD) was made based on the Mayo Sleep Questionnaire. Neuropsychological domains were assessed by Mini Mental State Examination, total score and figure copying, California Verbal Learning Test-II, Visual Object and Space Perception Cube and Silhouettes, Boston Naming Test, Stroop test, Verbal Category Fluency, Trail Making Test A and B. Results: Among the 246 subjects, 47 (19.1%) had pRBD at the baseline, and pRBD group was younger and with male predominance. During 4-year follow-up, we did not observe any significant differences in the rate of decline in neuropsychological measures. Patients with pRBD performed generally poorer in visuoconstructional, visuoperceptual, and executive/attention tests in comparison to RBD negative. Conclusion: We did not find any significant differences in progression rate of neurocognitive outcomes between dementia patients with and without RBD

A Longitudinal Study of Neurocognition in Dementia with Lewy Bodies Compared to Alzheimer’s Disease

IntroductionThere are relatively few longitudinal studies on the differences in cognitive decline between Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), and the majority of existing studies have suboptimal designs.AimWe investigated the differences in cognitive decline in AD compared to DLB over 4 years and cognitive domain predictors of progression.MethodsIn a longitudinal study, 266 patients with first-time diagnosis of mild dementia were included and followed annually. The patients were tested annually with neuropsychological tests and screening instruments [MMSE (Mini-Mental Status Examination), Clinical Dementia Rating (CDR), the second edition of California Verbal Learning Test (CVLT-II), Trail Making Test A &amp; B (TMT A &amp; B), Stroop test, Controlled Oral Word Associations Test (COWAT) animal naming, Boston Naming Test, Visual Object and Space Perception Battery (VOSP) Cubes and Silhouettes]. Longitudinal analyses were performed with linear mixed effects (LME) models and Cox regression. Both specific neuropsychological tests and cognitive domains were analyzed.ResultsThis study sample comprised 119 AD and 67 DLB patients. In TMT A, the DLB patients had a faster decline over 4 years than patients with AD (p = 0.013). No other longitudinal differences in specific neuropsychological tests were found. Higher executive domain scores at baseline were associated with a longer time to reach severe dementia (CDR = 3) or death for the total sample (p = 0.032). High or low visuospatial function at baseline was not found to be associated with cognitive decline (MMSE) or progression of dementia severity (CDR) over time.ConclusionOver 4 years, patients with DLB had a faster decline in TMT A than patients with AD, but this should be interpreted cautiously. Beyond this, there was little support for faster decline in DLB patients neuropsychologically than in AD patients

A longitudinal study of anxiety and cognitive decline in dementia with Lewy bodies and Alzheimer’ s disease

This article was originally published in the journal "Alzheimer's Research & Therapy". This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background Anxiety in dementia is common but not well studied. We studied the associations of anxiety longitudinally in Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Methods In total, 194 patients with a first-time diagnosis of dementia were included (n = 122 patients with AD, n = 72 patients with DLB). Caregivers rated the patients’ anxiety using the Neuropsychiatric Inventory, and self-reported anxiety was assessed with the anxiety and tension items on the Montgomery–Åsberg Depression Rating Scale. The Mini Mental State Examination was used to assess cognitive outcome, and the Clinical Dementia Rating (CDR)-Global and CDR boxes were used for dementia severity. Linear mixed effects models were used for longitudinal analysis. Results Neither in the total sample nor in AD or DLB was caregiver-rated anxiety significantly associated with cognitive decline or dementia severity over a 4-year period. However, in patients with DLB, self-reported anxiety was associated with a slower cognitive decline than in patients with AD. No support was found for patients with DLB with clinical anxiety having a faster decline than patients with DLB without clinical anxiety. Over the course of 4 years, the level of anxiety declined in DLB and increased in AD. Conclusions Anxiety does not seem to be an important factor for the rate of cognitive decline or dementia severity over time in patients with a first-time diagnosis of dementia. Further research into anxiety in dementia is needed

A systematic review of cognitive decline in dementia with Lewy bodies versus Alzheimer’s disease

The article was originally published in Alzheimer's Research & Therapy; and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Introduction: The aim of this review was to investigate whether there is a faster cognitive decline in dementia with Lewy bodies (DLB) than in Alzheimer’s disease (AD) over time. Methods: PsycINFO and Medline were searched from 1946 to February 2013. A quality rating from 1 to 15 (best) was applied to the included studies. A quantitative meta-analysis was done on studies with mini mental state examination (MMSE) as the outcome measure. Results: A total of 18 studies were included. Of these, six (36%) reported significant differences in the rate of cognitive decline. Three studies reported a faster cognitive decline on MMSE in patients with mixed DLB and AD compared to pure forms, whereas two studies reported a faster decline on delayed recall and recognition in AD and one in DLB on verbal fluency. Mean quality scores for studies that did or did not differ were not significantly different. Six studies reported MMSE scores and were included in the meta-analysis, which showed no significant difference in annual decline on MMSE between DLB (mean 3.4) and AD (mean 3.3). Conclusions: Our findings do not support the hypothesis of a faster rate of cognitive decline in DLB compared to AD. Future studies should apply recent diagnostic criteria, as well as extensive diagnostic evaluation and ideally autopsy diagnosis. Studies with large enough samples, detailed cognitive tests, at least two years follow up and multivariate statistical analysis are also needed