[Show abstract][Hide abstract] ABSTRACT: The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are the most commonly used scales to test cognitive impairment in Lewy body disease (LBD), but there is no consensus on which is best suited to assess cognition in clinical practice and most sensitive to cognitive decline. Retrospective cohort study of 265 LBD patients [Parkinson's disease (PD) without dementia (PDnD, N = 197), PD with dementia (PDD, N = 40), and dementia with Lewy bodies (DLB, N = 28)] from an international consortium who completed both the MMSE and MoCA at baseline and 1-year follow-up (N = 153). Percentage of relative standard deviation (RSD%) at baseline was the measure of inter-individual variance, and estimation of change (Cohen's d) over time was calculated. RSD% for the MoCA (21 %) was greater than for the MMSE (13 %) (p = 0.03) in the whole group. This difference was significant only in PDnD (11 vs. 5 %, p < 0.01), but not in PDD (30 vs. 19 %, p = 0.37) or DLB (15 vs. 14 %, p = 0.78). In contrast, the 1-year estimation of change did not differ between the two tests in any of the groups (Cohen's effect <0.20 in each group). MMSE and MoCA are equal in measuring the rate of cognitive changes over time in LBD. However, in PDnD, the MoCA is a better measure of cognitive status as it lacks both ceiling and floor effects.
Full-text · Article · Feb 2016 · Journal of Neural Transmission
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
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.
Full-text · Article · Jan 2016 · Alzheimer's Research and Therapy
[Show abstract][Hide abstract] ABSTRACT: Objective: To characterise the differences in caregiver distress between carers of people diagnosed with dementia with Lewy bodies (DLB) and people with Alzheimer's disease (AD), with a view to differentiating and improving support for caregivers. Methods: This study is a part of two larger Norwegian studies, DemVest (n=265) and The Norwegian Dementia Register (n=2220), with data from caregivers and people diagnosed with AD (n=100) and DLB (n=86) between 2005 and 2013. The average age was 74.9years (SD=7.8). Caregiver distress was rated by the Relative Stress Scale. Diagnosis of the person receiving care was based on a comprehensive standardised assessment program (International Classification of Diseases, Revision 10 or Diagnostic and Statistical Manual for Mental Disorders, fourth edition). Additional data collected from people receiving care were neuropsychiatric symptoms, comorbidity and activities of daily living (ADL) score. Linear regression analyses were applied, first unadjusted and then in stepwise-adjusts in addition to descriptive analyses. Results: Caregivers to people with AD (20.2%) and 40% of caregivers for people with DLB experienced moderate or high caregiver burden with an increased risk of psychiatric disorders in the early stage of dementia. High Relative Stress Scale (RSS) total scores in caregivers was significantly associated with neuropsychiatric symptoms (Neuropsychiatric Inventory, p=0.004) and also with impaired ADL functioning (Rapid Disability Rating Scale-2, p<0.0005). Conclusion: Caregiver distress differed (RSS total, p=0.005) between people caring for someone with AD (15.0) and those caring for someone with DLB (19.9). These findings have direct implications for the needs and resources that could be available for these individuals and indicate the need for further research into caregiver burden in carers to people with DLB.
No preview · Article · Jan 2016 · International Journal of Geriatric Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Cognition is often affected early in Parkinson’s disease (PD). Lewy body and amyloid β (Aβ) pathology and cortical atrophy may be involved. The aim of this study was to examine whether medial temporal lobe structural changes may be linked to cerebrospinal fluid (CSF) biomarker levels and cognition in early PD. PD patients had smaller volumes of total hippocampus, presubiculum, subiculum, CA2–3, CA4-DG, and hippocampal tail compared with normal controls (NCs). In the PD group, lower CSF Aβ38 and 42 were significant predictors for thinner perirhinal cortex. Lower Aβ42 and smaller presubiculum and subiculum predicted poorer verbal learning and delayed verbal recall. Smaller total hippocampus, presubiculum and subiculum predicted poorer visuospatial copying. Lower Aβ38 and 40 and thinner perirhinal cortex predicted poorer delayed visual reproduction. In conclusion, smaller volumes of hippocampal subfields and subhippocampal cortex thickness linked to lower CSF Aβ levels may contribute to cognitive impairment in early PD. Thirty-three early PD patients (13 without, 5 with subjective, and 15 with mild cognitive impairment) and NC had 3 T magnetic resonance imaging (MRI) scans. The MRI scans were post processed for volumes of hippocampal subfields and entorhinal and perirhinal cortical thickness. Lumbar puncture for CSF biomarkers Aβ38, 40, 42, total tau, phosphorylated tau (Innogenetics), and total α-synuclein (Meso Scale Diagnostics) were performed. Multiple regression analyses were used for between-group comparisons of the MRI measurements in the NC and PD groups and for assessment of CSF biomarkers and neuropsychological tests in relation to morphometry in the PD group.
[Show abstract][Hide abstract] ABSTRACT: Background:
A common polymorphism of the butyrylcholinesterase gene, the K-variant (BCHE-K) is associated with reduced butyrylcholinesterase (BuChE) activity. Insufficient studies exist regarding the frequency and role of BCHE-K in dementias.
To determine the association of BCHE-K and APOEɛ4 with diagnosis and rate of cognitive decline in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients.
Genomic DNA from 368 subjects (108 AD, 174 DLB, and 86 controls) from two routine clinical cohort studies in Norway; DemVest and TrønderBrain, were genotyped for BCHE-K and APOEɛ4. The mild dementia DemVest subjects received annual Mini-Mental State Examination assessments for five years.
BCHE-K frequency was lower DLB (33.9% ; p < 0.01) than in control subjects (51.2%), and was numerically lower in AD as well (38.9% ; p = 0.11). More rapid cognitive decline was associated with the APOEɛ4 genotype, but not with the BCHE-K genotype. In an exploratory analysis of patients who completed all five follow-up visits, there was greater cognitive decline in BCHE-K carriers in the presence of the APOEɛ4 allele than in the absence of these polymorphisms.
BCHE-K is associated with a reduced risk for AD and DLB whereas APOEɛ4 is associated with more rapid cognitive decline. The greater cognitive decline in individuals with both APOEɛ4 and BCHE-K alleles require prospective confirmation in well-controlled trials.
Full-text · Article · Jan 2016 · Journal of Alzheimer's disease: JAD
[Show abstract][Hide abstract] ABSTRACT: Background: the analgesic drug use has been reported to increase in general in nursing home patients. However, there is insufficient
evidence in terms of what agents are used, variations of use over time and to whom these drugs are prescribed.
Objective: we investigated the prescribing patterns of scheduled analgesic drugs in Norwegian nursing home patients from 2000 to 2011,
with the association to age, gender, cognitive function and type of nursing home unit.
Design: secondary analyses of four study samples (three observational studies and one randomised controlled trial).
Setting and subjects: nursing home patients included in study samples from 2000 (n = 1,926), 2004 (n = 1,163), 2009 (n = 850) and 2011 (n = 1,858) located in 14 Norwegian counties.
Methods: trend analyses of analgesic drug prescriptions. Percentages were described using t-test, χ2 and Mann–Whitney U test and multivariate logistic regression.
Results: the odds ratio for receiving any pain medication in 2011 compared with 2000 was 2.6 (95% CI 2.23–2.91), this is corresponding
to a 65% increase from 34.9 to 57.6%. The paracetamol prescription increased by 113%, from 22.7% in 2000 to 48.4% in 2011.
Strong opioids (fentanyl, buprenorphine, morphine, oxycodone) increased from 1.9% in 2000 to 17.9% in 2011 (P < 0.001), whereas non-steroidal anti-inflammatory drug prescription decreased, from 6.8 to 3.2%. In 2000, 2004 and 2009,
people with dementia received fewer analgesics compared with patients without dementia; no differences in analgesic drug use
between the groups were found in 2011.
Conclusions: the analgesic drug prescription increased significantly from 2000 to 2011, especially the use of paracetamol and strong opioids.
We also highlight a possible change from under-prescription of analgesic medication in people with dementia, to an equal amount
compared with patients without cognitive impairment.
[Show abstract][Hide abstract] ABSTRACT: Alpha-synuclein (α-syn) aggregations are the key pathological hallmark of dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), but are also frequently present in Alzheimer's disease (AD). Much remains unknown about the role of α-syn in the synapse and the wider role of synaptic dysfunction in these dementias. Changes in concentrations of key 'SNAP (Soluble N-ethylmaleimide Sensitive Factor Attachment Protein) Receptor' (SNARE) proteins as a consequence of alterations in the aggregation state of α-syn may contribute to synaptic dysfunction in patients with DLB, PDD, and AD and result in impaired cognition. We have studied a large cohort (n = 130) of autopsy confirmed DLB, PDD, AD, and control brains. Using semi-quantitative western blotting, we have demonstrated significant changes across the diagnostic groups of DLB, PDD, and AD in the SNARE and vesicle proteins syntaxin, Munc18, VAMP2, and monomeric α-syn in the prefrontal cortex, with a significant reduction of Munc18 in AD patients (p < 0.001). This correlated to the final MMSE score before death (p = 0.016). We also identified a significant negative correlation between the duration of dementia and the levels of the binding partners VAMP2 (p = 0.0004) and monomeric α-syn (p = 0.0002). Our findings may indicate that an upregulation of SNARE complex related proteins occurs in the early stages of disease as an attempt at compensating for failing synapses, prior to widespread deposition of pathological α-syn.
No preview · Article · Dec 2015 · Journal of Alzheimer's disease: JAD
[Show abstract][Hide abstract] ABSTRACT: Background:
Mild cognitive impairment and dementia are common, clinically important features of Parkinson's disease (PD). The underlying disease pathology is heterogeneous and not yet well characterized. Biomarkers for cognitive impairment in PD could aid in diagnostic and prognostic evaluation and in the development of new cognitive enhancing treatments.
To examine the relationship between CSF markers and cognition in a large, multicentre, cohort study of early, untreated PD, and compare marker concentrations between PD patients with and without MCI and healthy, age-matched controls.
414 early, untreated PD (34% with mild cognitive impairment) and 189 healthy, cognitively intact controls with baseline neuropsychological testing and CSF abeta42, t-tau, p-tau181 and α-synuclein results were included. Multiple linear regression models were constructed with a composite cognition factor, or memory-, or visuospatial- or executive-attention domains as dependent variables, and CSF markers, demographic characteristics and MDS-UPDRS III score as predictors.
Lower α-synuclein was associated with reduced performance on the executive-attention domain and the composite cognition factor in the whole PD-group. Abeta42 was significantly decreased in PD with mild cognitive impairment compared with controls after adjusting for covariates, while values in PD without MCI were identical to healthy controls.
The association between reduced CSF α-synuclein concentrations and cognition suggests that α-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson's disease are associated with the risk of future cognitive decline and dementia.
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Nov 2015 · Neurodegenerative Diseases
[Show abstract][Hide abstract] ABSTRACT: Cerebrospinal fluid (CSF) has been extensively studied to explore biochemical alterations in subjects with neurodegenerative disorders. In Alzheimer's disease (AD), levels of increased CSF tau protein and decreased levels of β-amyloid 1-42 (Aβ42) have been shown to correlate with brain plaque formation and tangle pathology. Intracellular Lewy inclusions containing aggregated α-synuclein (α-syn) represent a pathological hallmark of Parkinson's disease (PD). In most-but not all-studies published to date total CSF α-syn concentrations have been found to be decreased in disorders related to α-syn pathology, i.e., PD, dementia with Lewy-bodies and multiple system atrophy. However, these reports show extensive signal overlap among tested individuals, thereby diminishing its potential for routine use in clinical practice. To investigate potential biological (i.e., non-technical) confounders of reported CSF levels for α-syn, Aβ42 and tau in PD and related disorders, we carried out a methodical review of known factors that underlie signal variability and speculate on those that have not yet been tested. We discuss several biological factors, such as neuropathology, demographics, clinical phenotype, progression and duration of disease, concomitant illnesses and, last but not least, pharmacotherapy, which in isolation or combination can substantially alter values for CSF proteins of interest. Enhanced implementation of standardized clinical protocols, streamlined operating procedures, and further progress in the development of validated assays for CSF proteins have the potential to (1) inform us as to the pathogenesis of disease, (2) support the laboratory-based diagnosis for symptomatic subjects in the future, and (3) facilitate breakthrough therapies to alter the course of neurodegenerative disorders, such as PD and AD. This article is protected by copyright. All rights reserved.
No preview · Article · Oct 2015 · Journal of Neurochemistry
[Show abstract][Hide abstract] ABSTRACT: The broad importance of dementia is undisputed, with Alzheimer's disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson's disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson's disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments.
[Show abstract][Hide abstract] ABSTRACT: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share clinical and pathological similarities. The defining features are motor parkinsonism and cognitive impairment, often accompanied by visual hallucinations, fluctuating consciousness, autonomic and sleep disturbances, and a number of other non-motor symptoms. Mild cognitive impairment (MCI) can be identified in 15% of PD patients at time of diagnosis, and may even precede motor symptoms. MCI usually progresses further, and dementia is a common endpoint. Cognitive impairment is usually the initial symptom of DLB, and the disease course is severe. A variety of biomarkers can assist in the diagnosis and prognosis of PD and DLB, including structural and functional imaging, cerebrospinal fluid, and EEG. Compared to the many treatments available for motor symptoms, relatively few systematic studies exist to guide the treatment of cognitive impairment in PD, and even less in DLB. However, there is good evidence for cholinesterase inhibitors in both DLB and PD with dementia, and some indications that memantine is helpful. Emerging evidence suggest that physical exercise and cognitive training are also effective, as are some reports of various brain stimulation techniques. Disease-modifying agents that delay the rate of cognitive decline in PD and DLB are urgently needed.
No preview · Article · Sep 2015 · Parkinsonism & Related Disorders
[Show abstract][Hide abstract] ABSTRACT: Background:
Autoantibodies with agonist function are described in cardiovascular disorders. Since vascular risk factors are associated with an increased risk for Alzheimer's disease (AD), we investigated a potential association between antibodies to the angiotensin 2 type 1 receptor (anti-AT1R) and AD.
The primary objective of this study was to investigate the association between anti-AT1R and AD. The secondary objective was to investigate the association between clinical or biomarker features of AD and anti-AT1R.
Samples from patients with mild AD participating in a longitudinal study in Western Norway (n = 92, 65 [71%] females, mean age 74.8 [range 50-89]) and age- and gender-matched healthy controls (n = 102) were included. Cerebrospinal fluid (CSF) AD biomarkers were assessed in a subgroup of patients. Patients were examined annually, including Mini-Mental State Examination. ELISA was used to measure anti-AT1R in serum. Non-parametric tests were used for statistical calculations and a p < 0.05 was considered significant.
AD patients had significantly higher levels of anti-AT1R compared with healthy controls (10.2 U/mL versus 8.1 U/mL, p = 0.04). This difference was found only in patients without hypertension and diabetes. Anti-AT1R levels correlated with CSF total tau (p = 0.03) and phosphorylated tau (p = 0.03) levels, and inversely with blood pressure in AD (Spearman R -0.277, p = 0.008).
AD is associated with increased levels of anti-AT1R, and the antibodies correlated with CSF total, and phosphorylated tau levels. Further research is needed to understand the blood pressure response in AD without hypertension and a potential link between tau and anti-AT1R in AD.
No preview · Article · Sep 2015 · Journal of Alzheimer's disease: JAD
[Show abstract][Hide abstract] ABSTRACT: Background:
Nursing home patients have complex mental and physical health problems, disabilities and social needs, combined with widespread prescription of psychotropic drugs. Preservation of their quality of life is an important goal. This can only be achieved within nursing homes that offer competent clinical conditions of treatment and care. COmmunication, Systematic assessment and treatment of pain, Medication review, Occupational therapy, Safety (COSMOS) is an effectiveness-implementation hybrid trial that combines and implements organization of activities evidence-based interventions to improve staff competence and thereby the patients' quality of life, mental health and safety. The aim of this paper is to describe the development, content and implementation process of the COSMOS trial.
COSMOS includes a 2-month pilot study with 128 participants distributed among nine Norwegian nursing homes, and a 4-month multicenter, cluster randomized effectiveness-implementation clinical hybrid trial with follow-up at month 9, including 571 patients from 67 nursing home units (one unit defined as one cluster). Clusters are randomized to COSMOS intervention or current best practice (control group). The intervention group will receive a 2-day education program including written guidelines, repeated theoretical and practical training (credited education of caregivers, physicians and nursing home managers), case discussions and role play. The 1-day midway evaluation, information and interviews of nursing staff and a telephone hotline all support the implementation process. Outcome measures include quality of life in late-stage dementia, neuropsychiatric symptoms, activities of daily living, pain, depression, sleep, medication, cost-utility analysis, hospital admission and mortality.
Despite complex medical and psychosocial challenges, nursing home patients are often treated by staff possessing low level skills, lacking education and in facilities with a high staff turnover. Implementation of a research-based multicomponent intervention may improve staff's knowledge and competence and consequently the quality of life of nursing home patients in general and people with dementia in particular.
[Show abstract][Hide abstract] ABSTRACT: Parkinson's disease (PD) is characterized by motor symptoms, but focused and extensive research in the last years has provided new knowledge in the field of non-motor symptoms. Non-motor symptoms include neuropsychiatric symptoms such as depression, anxiety, psychosis, apathy, impulse control disorders, and occur in the majority of patients with PD. They are associated with impaired quality of life for patients and relatives, additional deterioration of function and increased use of health resources. Medical and surgical therapies commonly used for treatment of PD can induce or worsen such symptoms. This paper discusses the epidemiology, clinical features and treatment approaches for neuropsychiatric symptoms (NPS) in PD in the perspective of clinical practice and management. The prevalence rates of various NPS are high, various demographic, clinical and treatment related variables have shown to be associated with higher risk of NPS. Randomized controlled trials of pharmacological and non-pharmacological treatments of NPS in PD are sparse. Current evidence supports tricyclic antidepressants as efficacious treatment of depression in PD and antipsychotic clozapine as efficacious choice for psychosis. Further studies to evaluate various other management strategies of NPS in PD are required. Neuropsychiatric symptoms in PD should be considered an integral part of the disease; hence a multidisciplinary approach is essential to improve the overall outcome of PD also through raised awareness and enriched knowledge on NPS.