Time until nursing home admission in people with mild dementia: comparison of dementia with Lewy bodies and Alzheimer's dementia.

OBJECTIVE: We studied time until nursing home admission (NHA) in mild dementia and predictors for NHA in people with Dementia with Lewy bodies (DLB) and how it compares to Alzheimer's dementia (AD). METHODS: Kaplan-Meier survival analysis and Cox proportional hazards were applied. RESULTS: Median time until NHA was 1114 days (95% confidence interval [CI] [932, 1296]). In DLB median time until NHA was 663 days [472, 998]) as compared with 1336 days (1068, 1606) in AD, p < 0.0005. Predictors of shorter time to NHA in the DLB and AD groups in unadjusted analyses were a DLB diagnosis, the use of antipsychotic medication, more advanced age, longer duration of dementia symptoms prior to diagnosis, living alone, higher reported caregiver distress, and more neuropsychiatric symptoms. The use of cholinesterase inhibitors was associated with halved risk of NHA in the combined DLB/AD group in the unadjusted Cox regression. In adjusted Cox regression in the DLB group, we found the use of cholinesterase inhibitors to be associated with reduced risk of NHA (HR = 0.24) and the use of antipsychotic medication to be associated with increased risk of NHA (HR = 37) during the study period. CONCLUSION: Patients diagnosed with DLB had nearly 2 years shorter time to NHA than those diagnosed with AD. In the DLB group, the use of cholinesterase inhibitors was associated with reduced and the use of antipsychotics with increased risk of NHA. Future studies should explore whether better identification and management of the variety of clinical problems in patients diagnosed with DLB can delay NHA.

Depression in mild dementia: associations with diagnosis, APOE genotype and clinical features.

BACKGROUND: Depression is common in dementia, with important clinical implications. Few studies of depression in dementia with Lewy bodies are available, and the results are inconsistent. OBJECTIVE: To examine the frequency of depression and its characteristics and correlates, in people with mild dementia. METHODS: All referrals for patients with a first time diagnosis of dementia to geriatric and older psychiatry outpatient clinics in the counties of Rogaland and Hordaland in Western Norway from March 2005 to March 2007 were screened for the study. Participants and their caregivers underwent a comprehensive and standardised diagnostic and assessment procedure. The depression subitem of the neuropsychiatric inventory (NPId) and Montgomery and Åsberg depression rating scale (MADRS) were used to estimate depression. Cut-off scores for any depression were 0/1 (NPId) and 6/7 (MADRS), and for clinically significant depression 3/4 and 14/15, respectively. RESULTS: Two hundered and twenty-three subjects with dementia participated, of whom 59 and 50% showed symptoms of depression assessed by NPI or MADRS, respectively, and 25 and 16% had clinically significant depression as measured by NPI and MADRS, respectively. Depression was more frequent in dementia with Lewy bodies (DLB) than in Alzheimer's disease (AD; p < 0.05). APOE genotype was available in 153 patients, and in AD, but not in DLB, a general linear model showed that the presence of APOEε4 allele was significantly associated with depression (F = 4.14; p = 0.045). CONCLUSION: Depression is common even in mild dementia, and more common and severe in DLB compared to AD. Future studies should explore the longitudinal course of depression in DLB, and the neural underpinnings of depression in DLB.

High prevalence of orthostatic hypotension in mild dementia.

BACKGROUND/AIMS: Orthostatic hypotension (OH) and QTc prolongation have potentially important prognostic and therapeutic consequences but have rarely been studied in patients with mild dementia. METHODS: Patients with mild dementia were diagnosed according to consensus criteria after comprehensive standardized assessment. OH and QTc were assessed using standardized criteria. RESULTS: OH was significantly more common in the dementia than in the control group, and systolic drop was higher in those with dementia with Lewy bodies. There were no significant differences in QTc values between dementia and control subjects. CONCLUSION: OH occurs even in patients with mild dementia, in particular in dementia with Lewy bodies. QTc was not prolonged in patients with mild dementia compared with normal controls.

Early discriminatory diagnosis of dementia with Lewy bodies. The emerging role of CSF and imaging biomarkers.

BACKGROUND: The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer's disease (AD). METHOD: We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB. RESULTS: The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid beta (abeta) isoforms as well as alpha-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level. CONCLUSION: Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.

Neuropsychiatric correlates of cerebrospinal fluid biomarkers in Alzheimer's disease.

BACKGROUND: The aim of this study was to explore the relationship between cerebrospinal fluid biomarkers and neuropsychiatric symptoms in people with Alzheimer's disease. Psychosis, agitation, apathy and depression were assessed using standardised measures in 32 patients with mild Alzheimer's disease. METHODS: The levels of the 42-amino-acid form of beta-amyloid (A beta(1-42)), tau and p-tau (phosphorylated at threonine 181) were quantified using the conventional enzyme-linked immunosorbent assay method. RESULTS: Our result shows that apathy is significantly correlated with tau and p-tau but not with A beta(1-42). There were no significant correlations between indices of psychosis/agitation,or depression and cerebrospinal fluid A beta(1-42), tau or p-tau concentrations. CONCLUSION: Our finding suggests that apathy is associated with the level of neurofibrillary tangles in people with mild Alzheimer's disease. In contrast, the overall levels of neurofibrillary tangles or amyloid plaques do not seem to be associated with depression or psychosis, indicating that other brain changes contribute to these symptoms.

Frequency and case identification of dementia with Lewy bodies using the revised consensus criteria.

OBJECTIVE: To find the proportion of dementia with Lewy bodies (DLB) in a referral cohort of patients with a first-time diagnosis of mild dementia. BACKGROUND: The proportion of DLB among the dementia sufferers is not known and the clinical consensus criteria have low sensitivity. We employed the revised DLB criteria to study the proportion with DLB in a community sample of patients with mild dementia. METHODS: From March 2005 to March 2007, we included 196 patients from referrals to all geriatric medicine, old age psychiatry and neurology outpatient clinics in Rogaland and Hordaland counties in Western Norway. Standardized clinical instruments and diagnostic criteria were employed. RESULTS: 65% had Alzheimer dementia, 20% DLB (16% probable DLB), 5.6% vascular dementia, 5.6% Parkinson disease with dementia, 2.0% frontotemporal dementia and 1.5% alcoholic dementia. There were no significant differences in the proportion with DLB according to age bands and dementia severity groups. The revised criteria for a clinical diagnosis of DLB increased the proportion of probable DLB by 25% compared to the previous criteria. CONCLUSION: DLB is common in patients with mild dementia, and is the second most common type of dementia. The introduction of new clinical criteria for DLB leads to an increase in the proportion diagnosed with probable DLB.

White matter hyperintensities and the course of depressive symptoms in elderly people with mild dementia.

OBJECTIVES: To explore the relationship between white matter hyperintensities (WMH) and the prevalence and course of depressive symptoms in mild Alzheimer's disease (AD) and Lewy body dementia. DESIGN: This is a prospective cohort study conducted in secondary care outpatient clinics in western Norway. SUBJECTS: The study population consisted of 77 elderly people with mild dementia diagnosed according to standardised criteria. METHODS: Structured clinical interviews and physical, neurological, psychiatric, and neuropsychological examinations were performed and routine blood tests were taken. Depression was assessed using the depression subitem of the Neuropsychiatric Inventory and the Montgomery-Åsberg Depression Rating Scale (MADRS). A standardised protocol for magnetic resonance imaging scan was used, and the volumes of WMH were quantified using an automated method, followed by manual editing. RESULTS: The volumes of total and frontal deep WMH were significantly and positively correlated with baseline severity of depressive symptoms, and depressed patients had significantly higher volumes of total and frontal deep WMH than non-depressed patients. Higher volumes of WMH were also associated with having a high MADRS score and incident and persistent depression at follow-up. After adjustment for potential confounders, frontal deep WMH, in addition to prior depression and non-AD dementia, were still significantly associated with baseline depressive symptoms (p = 0.015, OR 3.703, 95% CI 1.294-10.593). Similar results emerged for total WMH. CONCLUSION: In elderly people with mild dementia, volumes of WMH, in particular frontal deep WMH, were positively correlated with baseline severity of depressive symptoms, and seemed to be associated with persistent and incident depression at follow-up. Further studies of the mechanisms that determine the course of depression in mild dementia are needed.