Higher Frequency and Complexity of Sleep Disturbances in Dementia with Lewy Bodies as Compared to Alzheimer's Disease.

BACKGROUND: Sleep disturbances (SDs) are common in patients with all forms of dementia. However, most studies focus on Alzheimer's disease (AD) and less is known about the prevalence and characteristics of SD in dementia with Lewy bodies (DLB). OBJECTIVE: The aims of this cross-sectional study were: (1) to examine the frequency of SD in DLB versus AD; (2) to compare patients with and without SD with regard to relevant clinical variables, and (3) to investigate the associations between SD and medication use. METHODS: Patients with a first-time diagnosis of probable or possible DLB or AD were selected from the Dementia Study of Western Norway and recruited from clinics for old age psychiatry from 2010 until the end of 2013. RESULTS: In all, 123 (55.7%) subjects with dementia suffered from at least one SD. Insomnia was present in 77 (34.8%), and 34 (20.7%) patients had probable REM-sleep behaviour disorder (RBD). All SDs were also significantly more frequent in patients with DLB than in AD, and DLB patients also more often had several co-occurring SDs. The presence of any SD was associated with more neuropsychiatric symptoms, higher morbidity, more parkinsonian symptoms and excessive daytime sleepiness. Antiparkinsonian medication was used more often in RBD, restless leg syndrome (RLS) and periodic limb movements, and benzodiazepines were also common in RLS. CONCLUSIONS: Sleep problems are more common in DLB patients compared to AD, and are associated with more clinical impairment. DLB patients frequently have several sleep problems occurring simultaneously, which suggests a need for screening and accurate assessment of sleep in DLB.

Cerebrospinal fluid neurofilament light chain mediates age-associated lower learning and memory in healthy adults.

Multiple cognitive domains, including learning, memory, and psychomotor speed, show significant reductions with age. Likewise, several cerebrospinal fluid (CSF) neurodegenerative biomarkers, including total tau (t-tau, a marker of neuronal body injury) and neurofilament light chain (NfL, a marker of axonal injury) show age-related increases in normal aging. In the current study, we aimed to investigate whether the age-effect within different cognitive domains was mediated by age-associated CSF markers for neurodegenerative changes. We fitted 10 mediation models using structural equation modeling to investigate this in a cohort of 137 healthy adults, aged 40-80 years, from the Norwegian Dementia Disease Initiation (DDI) study. Here, t-tau and NfL were defined as mediators between age and different cognitive tests. The models showed that NfL mediated the age-effect for CERAD learning and memory recall (learning: ß = -0.395, p < 0.05; recall: ß = -0.261, p < 0.01). No such effect was found in the other models. Our findings suggest that the age-related lower performance in verbal learning and memory may be linked to NfL-associated neurodegenerative changes in cognitively healthy adults.

The ANeED study - ambroxol in new and early dementia with Lewy bodies (DLB): protocol for a phase IIa multicentre, randomised, double-blinded and placebo-controlled trial.

Background: Currently, there are no disease-modifying pharmacological treatment options for dementia with Lewy bodies (DLB). The hallmark of DLB is pathological alpha-synuclein (aS) deposition. There are growing amounts of data suggesting that reduced aS clearance is caused by failure in endolysosomal and authophagic pathways, as well as and glucocerebrosidase (GCase) dysfunction and mutations in the GCase gene (GBA). The population's studies demonstrated that the incidence of GBA mutations is higher among Parkinson's disease (PD) patients, and carriers of such mutations have a higher risk of developing PD. The incidence of GBA mutations is even higher in DLB and a genome-wide association study (GWAS) confirmed the correlation between GBA mutations and DLB. In vivo experiments have shown that ambroxol (ABX) may increase GCase activity and GCase levels and therefore enhance aS autophagy-lysosome degradation pathways. Moreover, there is an emerging hypothesis that ABX may have an effect as a DLB modifying drug. The aims of the study "Ambroxol in new and early Dementia with Lewy Bodies (ANeED) are to investigate the tolerability, safety and effects of ABX in patients with DLB. Methods: This is a multicentre, phase IIa, double-blinded, randomised and placebo-controlled clinical trial, using a parallel arm design for 18 months' follow-up. The allocation ratio is 1:1 (treatment:placebo). Discussion: The ANeED study is an ongoing clinical drug trial with ABX. The unique, but not fully understood mechanism of ABX on the enhancement of lysosomal aS clearance may be promising as a possible modifying treatment in DLB. Trial Registration: The clinical trial is registered in the international trials register - clinicaltrials.com (NCT0458825) and nationally at the Current Research Information System in Norway (CRISTIN 2235504).

The frequency and correlates of anxiety in patients with first-time diagnosed mild dementia.

BACKGROUND: Anxiety in persons with dementia has received little attention despite its severe consequences. In this observational cross-sectional study, we investigated the frequency of anxiety and associations between anxiety and socio-demographic and clinical variables in an outpatient sample with first-time diagnosed mild dementia. METHODS: The study sample (n = 169) comprised participants recruited from clinics in geriatric medicine and old age psychiatry for a longitudinal dementia study. Symptoms of anxiety were rated by a caregiver on the Neuropsychiatric Inventory (NPI) and by the patient on the anxiety tension item on the Montgomery and Åsberg Depression Rating Scale. Measures of caregiver stress, dementia-related impairment (Clinical Dementia Rating (CDR) scale), and cognitive functioning were also included. RESULTS: According to caregiver reports, 19.5% had clinically significant anxiety and an additional 22.5% had subclinical anxiety. Half of the patients reported experiencing anxiety from time to time. Patients with Lewy-body dementia reported anxiety more often compared to patients with Alzheimer's disease. Anxiety was associated with depression, higher caregiver stress, and more dementia-related impairment, but not with cognitive test performance. Caregiver stress and higher CDR score increased the odds for anxiety significantly, even when controlling for depression. CONCLUSION: Anxiety is common in patients with mild dementia, and seems to be associated not so much with cognitive test performance than with caregiver distress and the patient's ability to function in daily life. Anxiety should be taken into account when assessing dementia, as well as screened for when examining patients with known dementia.

Cognitive Impairment After COVID-19-A Review on Objective Test Data.

Objective: The aim was to conduct a review on the literature on objective cognitive impairment in patients after COVID-19. Methods: We performed a literature review and searched Ovid Medline in February 2021 based on a PECO scheme. Results: Twelve articles met all inclusion criteria. Total patient sample was <1,000. All studies on global cognitive function found impairment, ranging from 15 to 80% of the sampled patients. Seven studies on attention and executive functions reported impairment, with varying results depending on sub-domain and different tests. Three out of four studies reported memory difficulties, with two studies reporting short-term memory deficits. Although results indicate possible language impairment, only one study used domain-specific language tasks. Two out of four studies on visuospatial function did not report any impairment. Conclusion: Patients with recent SARS-CoV-2 infection appear to experience global cognitive impairment, impairment in memory, attention and executive function, and in particular verbal fluency. Based on the current results, we recommend clinicians to evaluate the need for cognitive assessment of patients with a recent COVID-19 infection, regardless of the severity of the disease, treatment methods and length of ICU stay. We need studies with larger sample and control group.

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.

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.

Apathy is associated with faster global cognitive decline and early nursing home admission in dementia with Lewy bodies.

BACKGROUND: Little is known about the consequences of apathy in dementia with Lewy bodies (DLB), because previous research on apathy in dementia focused mainly on Alzheimer's disease (AD). METHODS: In this longitudinal study, we included patients with AD (n = 128) and patients with DLB (n = 81). At baseline, we analyzed the associations between apathy and cognition in the total sample and in AD and DLB separately. Generalized linear mixed models were used to investigate the association between apathy and Mini Mental State Examination (MMSE) over 4 years, and the Kaplan-Meier method was used to assess the association between apathy and survival or nursing home admission. RESULTS: In patients with DLB, apathy was associated with a faster global cognitive decline (MMSE) over 4 years. Patients with DLB and apathy had shorter time until nursing home admission than DLB patients without apathy and patients with AD, regardless of apathy. At baseline, patients with apathy had decreased performance on the Stroop color test and a composite executive function score. Neurocognition was unaffected by apathy in AD, but DLB patients with apathy had more verbal learning difficulties. CONCLUSIONS: Apathy seems to be associated with more serious symptomatology in DLB than in AD. It is important to focus on apathy in dementia because it is one of the most prevalent and disturbing behavioral and psychological symptoms.

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.

Neurocognitive Deficits Distinguishing Mild Dementia with Lewy Bodies from Mild Alzheimer's Disease are Associated with Parkinsonism.

BACKGROUND: The cognitive profile of mild dementia with Lewy bodies (DLB) versus mild Alzheimer's disease (AD) has not been extensively studied, and the relation of cognitive deficits to the core diagnostic criteria for DLB (fluctuations, visual hallucinations, and parkinsonism) remains poorly understood. OBJECTIVE: To compare the cognitive profile in patients with mild DLB to patients with mild AD and investigate the relation between cognitive deficits distinguishing DLB from AD and the core diagnostic features in DLB. METHODS: Patients with mild dementia were recruited from the southwestern part of Norway and patients diagnosed with probable AD (n = 113) or probable DLB (n = 77) were included. The DLB core diagnostic symptoms were assessed using standardized clinical measures, and standardized neurocognitive tests assessing attention, language, memory, and visuospatial functions were administered. Univariate and multivariate comparisons of cognitive tests were performed, and tests distinguishing between AD and DLB were subjected to correlational analyses with the core diagnostic symptoms. RESULTS: DLB patients performed worse than AD patients on test of visuoconstruction, but not visual perception and on all tests involving attention and executive functions, except verbal fluency. The multivariate model distinguished between DLB and AD with a sensitivity of 74% and a specificity of 82%. Tests where DLB performed worse than AD were highly correlated with degree of parkinsonism, but not with cognitive fluctuations or visual hallucinations. CONCLUSIONS: The cognitive profile in mild DLB can be useful in distinguishing AD from DLB. The strong relation between relative deficits in DLB and parkinsonism warrants further studies.

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

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.

Psychological characteristics of patients with chronic obstructive pulmonary disease: a review.

OBJECTIVE: The aim of this study was to review research on psychological characteristics in chronic obstructive pulmonary disease (COPD) patients and to summarize the findings of associations between psychological variables and various aspects of life, illness, and health in COPD patients. METHODS: The following databases were searched: Medline, PsycINFO, and the Cochrane Library. RESULTS: A total of 81 studies, published between 1968 and 2004, was identified. The reviewed studies indicated that patients suffering from COPD have a high prevalence of psychological disorders and may function at a reduced level of efficiency due to neuropsychological impairments. Psychological characteristics also seemed to be associated with functional disability and reduced quality of life. CONCLUSION: Psychological characteristics are important variables that interact with physical symptoms, and they should be taken into account when treating COPD patients. More studies with rigorous methodological designs are needed to describe the role of psychological variables in COPD accurately and reliably.

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

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.

The effect of psychomotor physical therapy on subjective health complaints and psychological symptoms.

BACKGROUND AND PURPOSE: The objective of this study was to examine the effect of Norwegian psychomotor physical therapy on subjective health complaints and psychological symptoms. METHOD: A non-randomized waiting list controlled design was used. Physiotherapists in Norway recruited patients for a treatment group (n = 40) and waiting list control group (n = 22). Patients on the waiting list could only be included for 6 months, as they then started treatment. Symptoms registration was obtained from both groups at baseline and 6 months, and only for the treatment group also at 12 months. The following self-report forms were used; Subjective Health Complaints Inventory (SCH); Beck Depression Inventory-II (BDI-II); Spielberger State-Trait Anxiety Inventory-Trait (STAI-T); Bergen Insomnia Scale (BIS); Fatigue Questionnaire (FQ); Quality of Life Inventory (QOLI); The Client Satisfaction Questionnaire (CSQ). RESULTS: The patients had had widespread and clinically significant health problems for an average of 9 years upon entrance to the study. After 6 months in psychomotor physical therapy, all the measured symptoms in the treatment group were significantly reduced, but only quality of life was significantly reduced when compared to the waiting list control group. After 12 months in therapy, the patients in the treatment group had continued to improve on all measured variables. The symptoms of anxiety and depression, as well as quality of life, were improved from clinical to non-clinical level. CONCLUSIONS: Norwegian psychomotor physical therapy seems to have potential for reducing symptoms of subjective health complaints, depression, anxiety, insomnia, fatigue and improving quality of life, although the process takes time. Further research is needed to gain more rigorous data, and randomized controlled studies are highly welcomed.