Brain metabolism in Alzheimer disease and vascular dementia assessed by in vivo proton magnetic resonance spectroscopy

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimer's disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification.

Risk of incident stroke in patients with Alzheimer disease or vascular dementia

OBJECTIVE To explore the risk of ischemic stroke, hemorrhagic stroke, or TIA in patients with Alzheimer disease (AD) or vascular dementia (VD). METHODS We conducted a follow-up study with a nested case-control analysis using the UK-based General Practice Research Database. We included patients aged 65 years and older with an incident diagnosis of AD or VD between 1998 and 2008 and a comparison group of dementia-free patients. We estimated incidence rates of ischemic stroke, hemorrhagic stroke, or TIA in patients with AD, VD, or without dementia, and we calculated odds ratios with 95% confidence intervals (CIs) of developing such an outcome in patients with AD or VD, stratified by use of antipsychotic drugs. RESULTS We followed 6,443 cases with AD, 2,302 with VD, and 9,984 dementia-free patients over time and identified 281 cases with incident ischemic stroke, 139 with hemorrhagic stroke, and 379 with TIA. The incidence rates of ischemic stroke for patients with AD, VD, or no dementia were 4.7/1,000 person-years (PYs) (95% CI 3.8-5.9), 12.8/1,000 PYs (95% CI 9.8-16.8), and 5.1/1,000 PYs (95% CI 4.3-5.9), respectively. Compared with dementia-free patients, the odds ratio of developing a TIA for patients with AD treated with atypical antipsychotic drugs was 4.5 (95% CI 2.1-9.2). CONCLUSIONS Patients with VD, but not AD, have a markedly higher risk of developing an ischemic stroke than those without dementia. In patients with AD, but not VD, use of atypical antipsychotic drugs was associated with an increased risk of TIA.

Seizures in patients with Alzheimer's disease or vascular dementia: a population-based nested case-control analysis

PURPOSE Patients with Alzheimer's disease (AD) have an increased risk of developing seizures or epilepsy. Little is known about the role of risk factors and about the risk of developing seizures/epilepsy in patients with vascular dementia (VD). The aim of this study was to assess incidence rates (IRs) of seizures/epilepsy in patients with AD, VD, or without dementia, and to identify potential risk factors of seizures or epilepsy. METHODS We conducted a follow-up study with a nested case-control analysis using the United Kingdom-based General Practice Research Database (GPRD). We identified patients aged ≥65 years with an incident diagnosis of AD or VD between 1998 and 2008 and a matched comparison group of dementia-free patients. Conditional logistic regression was used to estimate the odds ratio (OR) with a 95% confidence interval (CI) of developing seizures/epilepsy in patients with AD or VD, stratified by age at onset and duration of dementia as well as by use of antidementia drugs. KEY FINDINGS Among 7,086 cases with AD, 4,438 with VD, and 11,524 matched dementia-free patients, we identified 180 cases with an incident diagnosis of seizures/epilepsy. The IRs of epilepsy/seizures for patients with AD or VD were 5.6/1,000 person-years (py) (95% CI 4.6-6.9) and 7.5/1,000 py (95% CI 5.7-9.7), respectively, and 0.8/1,000 py (95% CI 0.6-1.1) in the dementia-free group. In the nested case-control analysis, patients with longer standing (≥3 years) AD had a slightly higher risk of developing seizures or epilepsy than those with a shorter disease duration, whereas in patients with VD the contrary was observed. SIGNIFICANCE Seizures or epilepsy were substantially more common in patients with AD and VD than in dementia-free patients. The role of disease duration as a risk factor for seizures/epilepsy seems to differ between AD and VD.

Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia

RATIONALE: Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today. Current treatment options are few and limited due to substantial side effects. OBJECTIVES: The aim of the study was to measure the effect of the cannabinoid dronabinol on nocturnal motor activity. METHODS: In an open-label pilot study, six consecutive patients in the late stages of dementia and suffering from circadian and behavioral disturbances-five patients with Alzheimer's disease and one patient with vascular dementia-were treated with 2.5 mg dronabinol daily for 2 weeks. Motor activity was measured objectively using actigraphy. RESULTS: Compared to baseline, dronabinol led to a reduction in nocturnal motor activity (P=0.028). These findings were corroborated by improvements in Neuropsychiatric Inventory total score (P=0.027) as well as in subscores for agitation, aberrant motor, and nighttime behaviors (P<0.05). No side effects were observed. CONCLUSIONS: The study suggests that dronabinol was able to reduce nocturnal motor activity and agitation in severely demented patients. Thus, it appears that dronabinol may be a safe new treatment option for behavioral and circadian disturbances in dementia.

Examining carer stress in dementia: the role of subtype diagnosis and neuropsychiatric symptoms

INTRODUCTION: Caring for people with dementia incurs significant stress for carers. Stress has been related to the duration of caring role, the number of weekly hours provided and severity of cognitive impairment. What remains less clear is the impact of neuropsychiatric symptoms and subtype of dementia on carer stress and this study aimed to examine these. METHODS: Dementia carers were recruited for people with a range of dementia subtypes. Carers were interviewed using the Neuropsychiatric Inventory with the Carer Distress Scale. Cognitive fluctuations were assessed using the Dementia Cognitive Fluctuations Scale. All patients were also examined with The Cambridge Assessment for mental disorders in the elderly. RESULTS: Dementia diagnostic subtype, the presence of cognitive fluctuations and some neuropsychiatric symptoms (psychosis and mood disturbance) did predict carer stress (all at p < 0.01) but age, gender and severity of cognitive impairment did not (all p > 0.33). Carers of people with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) experienced more stress than those caring for patients with Alzheimer's disease and vascular dementia. Carer stress was associated with higher levels of psychosis, mood disturbances, daytime sleep and cognitive fluctuations in the person with dementia. CONCLUSIONS: This study identified the significant impact on carers of providing care for people with DLB and PDD dementia subtypes and also highlighted the significant impact of providing care for patients with high levels of psychosis, mood disturbances and cognitive fluctuations.

The dementia cognitive fluctuation scale, a new psychometric test for clinicians to identify cognitive fluctuations in people with dementia.

OBJECTIVES Cognitive fluctuation (CF) is a common feature of dementia and a core diagnostic symptom for dementia with Lewy bodies (DLB). CF remains difficult to accurately and reliably detect clinically. This study aimed to develop a psychometric test that could be used by clinicians to facilitate the identification of CF and improve the recognition and diagnosis of DLB and Parkinson disease, and to improve differential diagnosis of other dementias. METHODS We compiled a 17-item psychometric test for identifying CF and applied this measure in a cross-sectional design. Participants were recruited from the North East of England, and assessments were made in individuals' homes. We recruited people with four subtypes of dementia and a healthy comparison group, and all subjects were administered this pilot scale together with other standard ratings. The psychometric properties of the scale were examined with exploratory factor analysis. We also examined the ability of individual items to identify CF to discriminate between dementia subtypes. The sensitivity and specificity of discriminating items were explored along with validity and reliability analyses. RESULTS Participants comprised 32 comparison subjects, 30 people with Alzheimer disease, 30 with vascular dementia, 29 with DLB, and 32 with dementia associated with Parkinson disease. Four items significantly discriminated between dementia groups and showed good levels of sensitivity (range: 78.6%-80.3%) and specificity (range: 73.9%-79.3%). The scale had very good levels of test-retest (Cronbach's alpha: 0.82) and interrater (0.81) reliabilities. The four items loaded onto three different factors. These items were: 1) marked differences in functioning during the daytime; 2) daytime somnolence; 3) daytime drowsiness; and 4) altered levels of consciousness during the day. CONCLUSIONS We identified four items that provide valid, sensitive, and specific questions for reliably identifying CF and distinguishing the Lewy body dementias from other major causes of dementia (Alzheimer disease and vascular dementia).

Dementia in patients with atrial fibrillation and the value of the Hachinski ischemic score.

AIM To assess the prevalence of vascular dementia, mixed dementia and Alzheimer's disease in patients with atrial fibrillation, and to evaluate the accuracy of the Hachinski ischemic score for these subtypes of dementia. METHODS A nested case-control study was carried out. A total of 103 of 784 consecutive patients evaluated for cognitive status at the Ambulatory Geriatric Clinic had a diagnosis of atrial fibrillation. Controls without atrial fibrillation were randomly selected from the remaining 681 patients using a 1:2 matching for sex, age and education. RESULTS The prevalence of vascular dementia was twofold in patients with atrial fibrillation compared with controls (21.4% vs 10.7%, P = 0.024). Alzheimer's disease was also more frequent in the group with atrial fibrillation (12.6% vs 7.3%, P = 0.046), whereas mixed dementia had a similar distribution. The Hachinski ischemic score poorly discriminated between dementia subtypes, with misclassification rates between 46% (95% CI 28-66) and 70% (95% CI 55-83). In patients with atrial fibrillation, these rates ranged from 55% (95% CI 32-77) to 69% (95% CI 39-91%). In patients in whom the diagnosis of dementia was excluded, the Hachinski ischemic score suggested the presence of vascular dementia in 11% and mixed dementia in 30%. CONCLUSIONS Vascular dementia and Alzheimer's disease, but not mixed dementia, are more prevalent in patients with atrial fibrillation. The discriminative accuracy of the Hachinski ischemic score for dementia subtypes in atrial fibrillation is poor, with a significant proportion of misclassifications.