[show abstract][hide abstract] ABSTRACT: Context
Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the most common neurodegenerative dementia types. It is important to differentiate between them because of the differences in prognosis and treatment approaches.
Investigate if sparse partial least squares (SPLS) classification of cortical thickness measurements could differentiate between AD and DLB.
Two independent cohorts without MR-protocol alignment in Norway and Slovenia with 97 AD and DLB subjects were enrolled. Cortical thickness measurements acquired with Freesurfer were used in subsequent SPLS classification runs. The cohorts were analyzed separately and afterwards combined. The models were trained with leave-one-out cross validation and test datasets were used when available. To study the impact of MR-protocol alignment, the classifiers were additionally tested on sets drawn exclusively from the independent cohorts.
The obtained sensitivity/specificity/AUC values were 94.4/88.89/0.978 and 88.2/94.1/0.969 in the Norwegian and Slovenian cohorts, respectively. Both cohorts showed AD-associated pattern of thinning in mid-anterior temporal, occipital and subgenual cingulate cortex, whereas the pattern supportive for DLB included thinning in dorsal cingulate, posterior temporal and lateral orbitofrontal regions. When combining the cohorts, sensitivity/specificity/AUC were 82.1/85.7/0.948 for the training and 77.8/75/0.731 for the testing datasets with the same pattern-of-difference. The models tested on datasets drawn exclusively from the independent cohorts did not produce adequate accuracy.
SPLS classification of cortical thickness is a good method for differentiating between AD and DLB, relatively stable even for mixed data, but not when tested on completely independent data drawn from different cohorts (without MR-protocol alignment).
Journal of Neurology 08/2013; 260(4). · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Despite the frequency and importance of dementia associated with Parkinson’s disease (PDD) and dementia with Lewy bodies (DLB), there is relatively little evidence on which to base treatment. Evidence from meta-analysis suggests that rivastigmine can improve cognition and functioning in PDD and also reduce risk of falling. There is also evidence supporting its use in DLB. Recent evidence suggests that memantine may also be effective, particularly for PDD, although evidence is more conflicting. Memantine may also improve parkinsonism and dyskinesias. Few clinical trials of cognition in PD without dementia exist, but there is preliminary evidence for atomoxetine, memantine, and piribedil. There is a lack of systematic evidence for the treatment of visual hallucinations and depression in PDD and DLB. In addition, there is a need for studies of whether potentially disease-modifying agents can prevent or delay the progression to dementia in PD.
Current Neurology and Neuroscience Reports 08/2013; 12(5). · 3.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objectives: Behavioral and psychological symptoms like depression and anxiety often coexist with dementia, and create an additional burden for patients and their caregivers. Anxiety symptoms have been related to poorer cognitive performance and decline in functional status. Whether anxiety is a cause or consequence of dementia-related impairment has received little attention so far. Most studies have focused on patients with Alzheimer´s disease (AD) and less is known about anxiety in Dementia with Lewy Bodies (DLB). The aims of the study were to investigate changes in the frequency and severity of anxiety in patients with AD or DLB over time and to assess the temporal relationship between anxiety symptoms and dementia-related impairment. Methods: In this observational longitudinal study, the sample comprised outpatients with first-time diagnosed mild dementia (n=196, 65% Alzheimer´s dementia, 20% DLB) recruited from clinics in geriatric medicine and old age psychiatry in Rogaland and Hordaland counties in Western Norway. Standardized clinical instruments and diagnostic criteria were employed. The participants are followed up at four years after the baseline assessments.
[show abstract][hide abstract] ABSTRACT: Objectives: Nursing home admission (NHA) is a prognostic milestone and probably the single most important factor driving costs in people with dementia and dementia increases the risk of NHA about 5 times as compared to people without dementia. We have previously found persons diagnosed with dementia with Lewybodies (DLB) to have a faster admission rate to a nursing home as compared to persons diagnosed with Alzheimer's disease (AD) and others have shown that more neuropsychiatric symptoms predicts faster admission to a nursing home. We studied the impact from the 12 different subitems of the neuropsychiatric inventory (NPI) scale, frequency times intensity scores, as predictors for NHA in mild Dementia with Lewybodies (DLB) and how it compares to mild Alzheimer's dementia (AD) in a prospective cohort study. Methods: We applied Kaplan-Meyer survival analysis and adjusted Cox proportional hazard ratios (HR). Results: Two hundred twenty-nine referrals with mild dementia were included, 133 diagnosed with AD and 67 with DLB. Mean age was 76 years, mean MMSE was 24 and median time until NHA was 1070 days. In a fully adjusted model in the DLB group apathy/indifference predicted shorter time until NHA (HR=1.21 95% CI (1.06, 1.38) p=0.005) and in the AD group both disinhibition (HR=1.19 95% CI (1.06, 1.34) p=0.003) and irritability/lability (HR=1.10 95% CI (1.01, 1.21) p=0.037) predicted faster admission to a nursing home. Conclusions: Neuropsychiatric symptoms predict shorter time to NHA in mild dementia. Disinhibition and irritability/lability are the most important predictor in AD, compared to apathy in DLB.
[show abstract][hide abstract] ABSTRACT: Introduction. Depression is common in the elderly with a significant impact on the quality of life, and increased risk for developing dementia. However, the underlying structural brain changes are not well established.
Objectives. To investigate neuroanatomical correlates of depressive symptoms in elderly people with and without mild cognitive impairment (MCI).
Methods. 621 subjects with (n = 395) and without (n = 226) MCI selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included in the study. Geriatric Depression Scale (GDS-15) with a cut-off point of 6 was used to evaluate depression. All subjects had T1 3D MRI images acquired at multiple ADNI sites using a standardized MRI protocol. Image post-processing included steps for brain segmentation and cortex reconstruction, and was performed using the software Freesurfer. General linear modeling was used to investigate depression-associated brain differences in patients with and without MCI (using age and gender as nuisance covariates).
Results. No depression-associated differences in cortical thickness were observed in subjects without MCI, whereas MCI subjects with depressive symptoms revealed significant thinning in right parahippocampal, middle temporal, left parahippocampal and entorinal gyri compared to non-depressed MCI patients.
Conclusion. We found that depressive symptoms in elderly patients with MCI are associated with more severe atrophy in medial temporal area, suggesting a possible contribution of Alzheimer's pathology in the pathogenesis of depression in this group.
[show abstract][hide abstract] ABSTRACT: Both cerebrovascular disease (CVD) and depression are common conditions in the elderly, and there is emerging evidence of a bi-directional relationship: 1) depression can cause CVD and stroke, transient ischemic attack; and 2) subcortical CVD are associated with increased risk for depression. The frequency of poststroke depression is highest during the first month after the stroke, but remains high even after several years. Depression is associated with poorer functional prognosis and higher mortality after stroke. There is good evidence that severity of functional impairment, high neuroticism, low social support as well as genetic factors are associated with an increased risk for post-stroke depression. Deep white matter lesions are the most consistent imaging correlate of depression. Potential mechanisms mediating the association between depression and CVD are neuroinflammation and HPA-axis activation, fronto-subcortical circuit lesions, and serotonergic dysfunction. Antidepressants have demonstrated effect on poststroke depression in meta-analyses, and such drugs as well as vitamin B can reduce the incidence of depression in stroke survivors. In addition, serotonergic drugs may strengthen poststroke motor and cognitive recovery, potentially through restorative mechanisms. Psychotherapeutic strategies such as problem-solving therapy seem to be effective. There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis.
[show abstract][hide abstract] ABSTRACT: Background/Aims: To compare neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and dementia with Lewy bodies(DLB). Methods: Neuropsychiatric symptoms and caregiver distress were assessed using the Neuropsychiatric Inventory (NPI) in mild DLB (n = 57) and AD (n = 126), and compared across the two groups using non-parametric tests. Results: The DLB patients had a higher NPI totalscore (median 24 vs. 11.5, p < 0.005), more numerous symptoms (median 5 vs. 4, p = 0.001) and more clinically significant symptoms (3 vs. 1, p = 0.001). They also had higher item hallucinations (6 vs. 2, p < 0.005) and apathy (7 vs. 5, p = 0.002) subscores. Caregivers scored higher on the NPI total caregiver distress scale (12.5 vs. 6, p = 0.003). Conclusions: In mild dementia, DLB patients have more neuropsychiatric symptoms and more associated caregiver distress compared with AD.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to explore the load of white matter hyperintensities (WMH) in patients with Lewy body dementia (LBD) and compare to Alzheimer's disease (AD) and normal controls (NC).
Diagnosis of LBD and AD was made according to consensus criteria and cognitive tests were administered. MRI scans for 77 (61 AD and 16 LBD) patients and 37 healthy elderly control subjects were available for analysis. We segmented WMH from FLAIR images using an automatic thresholding technique and calculated the volume of WMH in several regions of the brain, using non-parametric tests to compare groups. Multivariate regression was applied.
There were no significant differences in WMH between AD and LBD. We found a significant correlation between total and frontal WMH and Mini-Mental State Examination (MMSE) and verbal fluency scores in the AD group, but not in the LBD group.
The WMH load in LBD was similar to that of AD. A correlation between WMH load and cognition was found in the AD group, but not in the LBD group, suggesting that vascular disease contributes to cognitive impairment in AD but not LBD.
Dementia and geriatric cognitive disorders extra. 01/2012; 2(1):481-95.
[show abstract][hide abstract] ABSTRACT: To characterize brain metabolic changes associated with mild cognitive impairment (MCI) in drug-naive patients with Parkinson disease (PD) using (18)F-fluorodeoxyglucose (FDG) and PET (FDG-PET).
This cross-sectional study included newly diagnosed patients with PD with MCI in single or multiple domain (PD-MCI; n =12) and without MCI (PD-nMCI; n =12), and healthy controls (n =12). The groups were matched for age. Moreover, the patient groups were matched for motor disability. All subjects underwent a FDG-PET study. Cerebral regional relative metabolic maps were compared in PD-MCI, PD-nMCI, and controls using regions of interest analysis (ROIs) and voxel-based analysis with statistical parametric mapping.
ROIs and voxel-based analyses revealed significant relative hypometabolism in the prefrontal, superior/inferior parietal, and associative occipital cortices as well as in the striatum in patients with PD-MCI relative to controls (p < 0.05) and to a lesser extent in patients with PD-nMCI. In contrast, patients with PD-nMCI did not show significant metabolic changes as compared to controls.
MCI in patients with PD is associated with cortical hypometabolism since the earliest stage, independent of therapy or motor disability. The early involvement of posterior cortical region, a pattern shared by advanced stages of PD-MCI and PD with dementia, could represent an early marker of dementia. The relevance of this pattern in predicting prodromal dementia has to be evaluated in longitudinal studies.
[show abstract][hide abstract] ABSTRACT: To examine the incidence rates of antipsychotic (AP) and antidepressant (AD) drug treatment in Norway and the proportions initiated in general practice and specialist care respectively.
Data on all prescriptions of APs and ADs dispensed to the general population in Norway from 1 January 2004 until 31 August 2009 were extracted from the Norwegian Prescription Database. This information was merged with data about general practitioners (GPs) from the Norwegian Regular General Practitioner Scheme.
One-year incidence rates per 1000 inhabitants were 3.4 for APs and 8.6 for ADs. GPs initiated 58% of APs and 73% of ADs, while psychiatrists initiated 15% and 6% respectively. Psychiatrists initiated treatment more often among younger patients, and they prescribed relatively newer drugs more commonly than GPs. A large share of incident users did not refill their prescriptions for APs (57%) or ADs (33%).
GPs have a key role as regards initiating treatment with APs and ADs in Norway, while psychiatrists' influence seems limited, particularly among older patients. Efforts for quality improvement of mental health care need to involve primary health care. In addition, an increased focus from psychiatrists towards the increasingly ageing part of the population seems requisite.
[show abstract][hide abstract] ABSTRACT: Advancing age is associated with high prevalence of both dementia and pain. Dementia is frequently accompanied by distressing behavioral and psychological symptoms, including agitation and aggression, particularly in nursing home patients. The etiology of agitation is multifactorial. It has been suggested that un-diagnosed and untreated pain may contribute to agitation in people with dementia. If this is correct, individual pain treatment could be of benefit in ameliorating agitation and other behavioral changes in people with dementia.
The objective of this paper is to conduct a systematic review of studies of whether pain medication can improve agitation in people with dementia.
A systematic search of the PubMed and Cochrane databases for the period 1992-2010 was performed, using dementia, agitation, aggression, depression, behavioral disturbances, behavioral and psychological symptoms (BPSD), pain, pain assessment, pain treatment, pain management, and analgesics as search terms. Inclusion criteria were: prospective studies including patients with dementia, interventions focusing on pain reduction, inclusion of a control condition, and outcome measures including agitation or other related behavioral disturbances.
Only three controlled trials were identified; all were cross-over trials, and two included small sample sizes (<50). Findings were inconsistent, and although some correlations were reported, these did not support the hypothesis that pain management reduced agitation.
There is a profound dearth of rigorous studies of the effect of pain treatment in patients with dementia and agitation. The available studies do not support the hypothesis that pain management reduces agitation in nursing-home patients with dementia. Randomized, controlled parallel-group studies are needed.
International Journal of Geriatric Psychiatry 02/2011; 26(10):1012-8. · 2.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: This 30-week extension trial was a continuation of the first double-blind randomized controlled trial (RCT) to study memantine in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The objective was to evaluate the presence of recurrence of symptoms upon drug withdrawal. Furthermore, the aim was to explore washout dynamics in order to inform clinical practice.
Patients were enrolled from psychiatric, memory and neurological outpatient clinics in Norway, Sweden and the UK. The trial comprised a 4-week washout period and a 26-week open-label treatment period. Outcome measures were presence of recurrence of symptom upon drug withdrawal, Clinical Global Impression of Change (CGIC) and modified motor Unified Parkinson's Disease Rating Scale (UPDRS).
recurrence of symptoms occurred more frequently (p=0.04) in patients receiving memantine (58%) than in patients receiving placebo (25%). There was a significant global deterioration (p=0.0003) during washout within the memantine group as measured by CGIC. The patients seemed to recover during the open-label treatment, however these findings were non-significant.
The findings inform clinical practice that any possible memantine-associated benefits might be rapidly lost after drug withdrawal. The magnitude of deterioration suggests a symptomatic rather than a disease-modifying effect of the drug. Open-label results should merely be considered inspiration for future trials.
International Journal of Geriatric Psychiatry 02/2011; 26(2):206-13. · 2.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: In studies of mild cognitive impairment (MCI) in Parkinson disease (PD), patients without dementia have reported variable prevalences and profiles of MCI, likely to be due to methodologic differences between the studies.
The objective of this study was to determine frequency and the profile of MCI in a large, multicenter cohort of well-defined patients with PD using a standardized analytic method and a common definition of MCI.
A total of 1,346 patients with PD from 8 different cohorts were included. Standardized analysis of verbal memory, visuospatial, and attentional/executive abilities was performed. Subjects were classified as having MCI if their age- and education-corrected z score on one or more cognitive domains was at least 1.5 standard deviations below the mean of either control subjects or normative data.
A total of 25.8% of subjects (95% confidence interval [CI] 23.5-28.2) were classified as having MCI. Memory impairment was most common (13.3%; 11.6-15.3), followed by visuospatial (11.0%; 9.4-13.0) and attention/executive ability impairment (10.1%; 8.6-11.9). Regarding cognitive profiles, 11.3% (9.7-13.1) were classified as nonamnestic single-domain MCI, 8.9% (7.0-9.9) as amnestic single-domain, 4.8% (3.8-6.1) as amnestic multiple-domain, and 1.3% (0.9-2.1) as nonamnestic multiple-domain MCI. Having MCI was associated with older age at assessment and at disease onset, male gender, depression, more severe motor symptoms, and advanced disease stage.
MCI is common in patients with PD without dementia, affecting a range of cognitive domains, including memory, visual-spatial, and attention/executive abilities. Future studies of patients with PD with MCI need to determine risk factors for ongoing cognitive decline and assess interventions at a predementia stage.
[show abstract][hide abstract] ABSTRACT: BACKGROUND:
Physical exercise has several beneficial effects, including reduced risk for Alzheimer's disease. Although several studies of potential risk factors for vascular dementia (VaD) exist, including physical activity, the studies have usually included few participants and there are no meta-analyses addressing this key topic.
The MEDLINE database was searched using the key words 'physical exercise' 'activity' or 'walking' in combination with 'dementia' and 'vascular dementia'. Potentially relevant studies were assessed and summarised by two of the authors, and longitudinal studies with operationalized definition of physical activity providing risk for VaD in both groups were included in the meta-analysis using pooled estimates from a random effects model.
A total of 24 longitudinal studies, including 1378 patients with VaD, were included in the review. The majority of individual studies did not report significant associations. Five studies fulfilled criteria for meta-analysis, including 10,108 non-demented control subjects and 374 individuals with VaD. The meta-analysis demonstrated a significant association between physical exercise and a reduced risk of developing VaD: OR 0.62 (95% CI 0.42-0.92).
We conclude that there is evidence supporting the hypothesis that physical activity is likely to prevent the development of VaD, and should be highlighted as part of secondary prevention programmes in people at risk for cerebrovascular disease.
Aging and Mental Health 05/2010; · 1.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: We investigated caregiver distress associated with neuropsychiatric problems in patients with newly diagnosed Parkinson's disease (PD).
Persons who were next of kins of 198 patients and 168 healthy individuals completed the Neuropsychiatric Inventory Caregiver Distress Scale.
Even at the time of diagnosis PD has a considerable impact on the next of kins' experience of distress. Nearly 50% reported distress, significantly more than in the control group, and more than one-quarter reported moderate severe distress. Except the more rarely reported neuropsychiatric symptoms, apathy was the symptom that most frequently caused caregiver distress in PD patient's next of kin (94.5%), followed by depression (88.2%), anxiety (86.2%) and irritability (83.3%).
The study underlines the importance of focusing on neuropsychiatric aspects in patients and associated caregiver distress even in early PD management.