Showing papers in "Dementia and Geriatric Cognitive Disorders in 2007"
TL;DR: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD.
Abstract: Background/Aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer's disease (AD). Methods: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. Results: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients. Conclusion: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD.
314 citations
TL;DR: The current state of knowledge about gait and cognition in general are reviewed along with an exploration of the association between dementia, gait impairment and falls in AD, and a new approach targeting cognition is proposed.
Abstract: Alzheimer's disease (AD) is generally understood as primarily affecting cognition while sparing motor function, at least until the later stages of the disease. Studies reported over the past 10 years, however, have documented a prevalence of falls in AD patients significantly higher than in age-matched normal elders; also persons with AD have been observed to have different walking patterns with characteristics that increase gait instability. Recent work in cognitive neuroscience has begun to demonstrate the necessity of intact cognition, particularly executive function, for competent motor control. We put the pieces of this puzzle together and review the current state of knowledge about gait and cognition in general along with an exploration of the association between dementia, gait impairment and falls in AD. We also briefly examine the current treatment of gait instability in AD, mainly exercise, and propose a new approach targeting cognition.
309 citations
TL;DR: Investigation of baseline levels of the 40- and 42-amino-acid-long Aβ peptides in cerebrospinal fluid from a cohort of patients with mild cognitive impairment points to the usefulness of the Aβ42/Aβ40 ratio as a predictive biomarker for AD.
Abstract: Evidence supports an important role for beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD). Here, we investigate baseline levels of the 40- and 42-amino-acid-long Abeta peptides (Abeta40 and Abeta42) in cerebrospinal fluid (CSF) from a cohort of patients with mild cognitive impairment (MCI, n = 137) in relation to the final diagnosis after 4-6 years of follow-up time. CSF Abeta42 concentration at baseline and the Abeta42/Abeta40 ratio were significantly decreased in the MCI patients who developed AD as compared to cognitively stable MCI patients and MCI patients who developed other forms of dementia (p < 0.001). The baseline levels of Abeta40 were similar in all MCI groups but correlated with change in Mini Mental State Examination scores in converters to AD. The Abeta42/Abeta40 ratio was superior to Abeta42 concentration with regard to identifying incipient AD in MCI (p < 0.05). In conclusion, the data provide further support for the view that amyloid precursor protein metabolism is disturbed in early sporadic AD and points to the usefulness of the Abeta42/Abeta40 ratio as a predictive biomarker for AD.
283 citations
TL;DR: The validity of dementia syndrome in the Danish hospital registers was high and allows for epidemiological studies about dementia, and Alzheimer’s disease, although underregistered, also had a good validity once the diagnosis was registered.
Abstract: Background:The validity of dementia diagnoses in the Danish nationwide hospital registers was evaluated to determine the value of these registers in epidemiological research about dementia. Methods: Two hundred patients were randomly selected from 4,682 patients registered for the first time with a dementia diagnosis in the last 6 months of 2003. The patients’ medical journals were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and specific dementia subtypes. The patients who were still alive in 2006 were invited to an interview. Results: One hundred and ninety-seven journals were available for review and 51 patients were interviewed. A registered diagnosis of dementia was found to be correct in 169 (85.8%) cases. Regarding dementia subtypes, the degree of agreement between the registers and the results of the validating process was low with a kappa of 0.36 (95% CI 0.24–0.48). Conclusion: The validity of dementia syndrome in the Danish hospital registers was high and allows for epidemiological studies about dementia. Alzheimer’s disease, although underregistered, also had a good validity once the diagnosis was registered. In general, other ICD-10 dementia subtypes in the registers had a low validity and are less suitable for epidemiological research.
219 citations
TL;DR: A meta-analysis supports memantine’s clinically relevant efficacy in patients with moderate to severe AD, and shows statistically significant effects for memantine in each domain.
Abstract: The efficacy of memantine in Alzheimer's disease (AD) has been investigated in multiple randomised, placebo-controlled phase III trials. Recently, the indication label for memantine in Europe was extended to cover patients with moderate to severe AD, i.e. Mini-Mental State Exam total scores below 20. The efficacy data for memantine in this patient subgroup has been summarised by a meta-analysis of 1,826 patients in six trials. Efficacy was assessed using measures of global status (Clinician's Interview-Based Impression of Change Plus Caregiver Input), cognition (Alzheimer's Disease Assessment Scale - Cognitive Subscale, or Severe Impairment Battery), function (Alzheimer's Disease Cooperative Study Activities of Daily Living 19- or 23-item scale), and behaviour (Neuropsychiatric Inventory). Results (without replacement of missing values) showed statistically significant effects for memantine (vs. placebo) in each domain. Memantine was well tolerated, and the overall incidence rates of adverse events were comparable to placebo. This meta-analysis supports memantine's clinically relevant efficacy in patients with moderate to severe AD.
207 citations
TL;DR: The findings suggest that some symptoms of dementia, such as agitation/aggression and irritability/lability, may affect the caregivers significantly, although their frequency and severity are low.
Abstract: Background: Despite many studies about the association between caregiver burden and behavioral and psychological symptoms of dementia (BPSD), there have been no population-based stu
205 citations
TL;DR: Depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia.
Abstract: Background: Neuropsychiatric disturbances are common in mild cognitive impairment (MCI). Depression and apathy may identify a subset of MCI subjects at higher risk of progression to
181 citations
TL;DR: MCI is frequent in elderly patients of GPs and a key position in secondary prevention and care of incipient cognitive deterioration up to the diagnosis of dementia, and positive associations were found for apoE Ε4 allele, vascular diseases and depressive symptoms.
Abstract: Background: Although mild cognitive impairment (MCI) represents a high-risk factor for developing dementia, little is known about the prevalence of MCI among patients of general pra
178 citations
TL;DR: The presence of SMC contributes to the risk of future decline, however, the increasing intensity of the perceived impairment does not further enhance the risk.
Abstract: Background/Aims: Subjective memory complaint (SMC) in normal individuals may predict future cognitive decline. The goal of this study was to examine whether the probability of decline increases with growing intensity of complaint. Methods: Normal subjects over the age of 50 years were included in a longitudinal retrospective study (mean follow-up time = 8 years). All subjects (n = 230) underwent cognitive and medical examination at baseline. The presence of SMC was determined based on Global Deterioration Scale staging. A subgroup of 83 participants also received baseline assessment for the intensity of SMC. Logistic regression was used to predict outcome from baseline variables. Three outcome groups were established at the final visit: nondeclining, declining and diagnostically unstable (i.e. the diagnosis changed over time: from normal to mild cognitive impairment, then back to normal). Results: The presence of SMC was a predictor of future decline but also increased the likelihood of the unstable diagnosis. Increasing intensity of SMC did not further raise the risk for decline. High intensity of complaints and more pronounced affective symptoms predicted the unstable clinical diagnosis. Conclusions: The presence of SMC contributes to the risk of future decline, however, the increasing intensity of the perceived impairment does not further enhance the risk.
172 citations
TL;DR: There was a significant linear association between apathy severity and cortical gray matter atrophy in the bilateral anterior cingulate and left medial frontal regions in AD.
Abstract: Background: Apathy is the most common noncognitive symptom inAlzheimer’s disease (AD). The structural correlates of apathy in AD have not yet been described. Methods:
170 citations
TL;DR: Low levels of baseline β-amyloid 1–42 were associated with development of subjective memory impairment affecting quality of life (memQoL), with a worse Mini Mental Status Examination score and with inability to live in regular housing at follow-up.
Abstract: Objective: To investigate whether cerebrospinal fluid (CSF) biomarkers can predict cognitive decline in healthy, elderly individuals as they have been shown to do in cognitively imp
TL;DR: MRI findings should form part of the diagnostic criteria for SD; the absence of atrophy on MRI in many behavioural cases raises the prospect that the behavioural syndrome of FTD is not specific for patients with a neurodegenerative disease.
Abstract: Background/Aims: The status of imaging findings in the clinical diagnosis of frontotemporal dementia (FTD) remains uncertain; while they may be supportive of a diagnosis of frontote
TL;DR: In elderly women, metabolic syndrome may be an important contributor to worsening of memory, which is an essential part of mild cognitive impairment.
Abstract: Objective: To test the hypothesis that metabolic syndrome predicts cognitive impairment, and to examine the association of single metabolic risk factors with cognitive functioning.
TL;DR: The MeSy was not associated with an increased dementia risk in a multiethnic elderly cohort, but diabetes andhyperinsulinemia were, and in the elderly, examining diabetes and hyperinsulininemia separately may be preferable to using the MeSy as a risk factor.
Abstract: Background/Aims: The metabolic syndrome (MeSy) may be related to Alzheimer’s disease (AD). Our aims were to investigate the association of the MeSy with incident dementia in a multi
TL;DR: Celecoxib 200 mg bid did not slow the progression of AD in this study, and the occurrence of adverse events was as expected for an elderly population with a complex chronic medical condition.
Abstract: Background/Aims: Cyclooxygenase-2 (COX-2) may play an important role in the neuropathology of Alzheimer’s disease (AD). The efficacy and safety of celecoxib (200 mg bid), a COX-2 selective inhibitor, were assessed in patients ≧50 years with established mild-to-moderate AD to determine whether treatment was effective in retarding deterioration of cognitive function. Methods: This was a 52-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The primary efficacy end points were the change from baseline to week 52 in the Alzheimer’s Disease Assessment Scale-Cognitive Behavior (ADAS-cog) composite score and the week 52 Clinician’s Interview-Based Impression of Change Plus (CIBIC+). Results: At 52 weeks, change in ADAS-cog scores from baseline was similar for placebo and celecoxib 200 mg bid groups (5.00 and 4.39, respectively). CIBIC+ scores were also similar (4.83 and 4.92). Two extension studies were conducted but were terminated early based on these efficacy results. Safety data from all 3 studies indicated that celecoxib was generally well-tolerated. Conclusion: Celecoxib 200 mg bid did not slow the progression of AD in this study, and the occurrence of adverse events was as expected for an elderly population with a complex chronic medical condition.
TL;DR: In this group of nondepressed outpatients meeting criteria for probable AD, apathetic subjects displayed significant perfusion differences compared to nonapathetic subjects.
Abstract: Background/Aims: To assess the association between regional cerebral blood flow (rCBF) and apathy in Alzheimer’s Disease (AD). Methods: SPECT and MRI scans were obtained from 51 nondepressed outpatients meeting criteria for probable AD (age 77.6 ± 6.6 years; MMSE 22.3 ± 5.1; 23 apathetic, 28 nonapathetic) and 23 healthy elderly (75.6 ± 3.8 years) controls. The following regions of interest (ROIs) were compared between apathetic and nonapathetic AD patients and then referenced against aged controls: anterior cingulate, orbitofrontal cortex, middle medial temporal cortex, hippocampus, medial superior temporal cortex, thalamus/hypothalamus and pons. Results: Apathetic and nonapathetic patients had significant differences in rCBF. Relative to nonapathetic AD patients, apathetic AD patients had lower perfusion in 2 ROIs (right orbitofrontal cortex and left anterior cingulate) and higher perfusion in 5 ROIs (right and left hippocampi, left medial superior temporal gyrus, and right and left middle medial temporal cortex). Comparison of rCBF in these 7 ROIs to healthy elderly controls confirmed hypoperfusion in the left anterior cingulate and right orbitofrontal cortex and suggested a relative sparing of perfusion among apathetic AD patients in the remaining 5 ROIs. Conclusions: In this group of nondepressed patients with AD, apathetic subjects displayed significant perfusion differences compared to nonapathetic subjects.
TL;DR: DM1 patients with more than 30 years ofDM have a similar cognitive profile and better MRI ratings than age- and education-matched DM2 patients with only 7 years of DM, which is similar to other types of diabetes mellitus.
Abstract: Background/Aims: Diabetes mellitus (DM) may affect the central nervous system, resulting in cognitive impairments. It has been suggested that cognitive impairments are more pronounc
TL;DR: Statin use did not show a beneficial effect on the risk of dementia or Alzheimer’s disease, and further study and independent confirmation of the association between statin use and dementia and Alzheimer's disease in larger clinical trials are warranted.
Abstract: Background/Aim: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are thought to reduce the amount of Abeta peptides by reducing cholesterol from blood and/or cer
TL;DR: The results support a fast impairment of complex visual functions in hallucinating PD patients, but also a progressive decline in multiple cognitive domains, which have been identified as a risk of developing dementia in PD.
Abstract: Objective: To evaluate the decline in specific neuropsychological functions in nondemented Parkinson’s disease (PD) patients with a history of visual hallucinations (VH). M
TL;DR: It is concluded that structural brain change is associated with the APOE genotype and that it is more salient in younger ageing individuals.
Abstract: Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer’s disease (AD) and has also been implicated in cardiovascular disease, cognitive decline and cognit
TL;DR: Valproate is not effective for the management of agitation in moderate-to-severe AD, and may be poorly tolerated in this population of institutionalized AD patients.
Abstract: Background/Aims: To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer’s disease (AD). Methods:
TL;DR: APOE Ε4 allele appears to significantly impact rate of volume loss over time in the hippocampus in nondemented older adults, and detailed cognitive characterization of the sample is necessary to reliably interpret the relationship between cognition and brain structure.
Abstract: Background/Aims: Because of conflicting findings across studies, we sought to better determine the relationship between apolipoprotein E (APOE) genotype, hippocampal volume, and cog
TL;DR: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting, better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation.
Abstract: Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer’s disease. The outcome of continuous long-term treatment in
TL;DR: The factor structure of the NPI-NH in nursing home patients is consistent with the clinical taxonomy of symptoms, is relatively stable across dementia stages, and is only moderately influenced by psychoactive medication use.
Abstract: Background/Aims: To examine the influence of dementia stage and psychoactive medication use on the factor structure of the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) i
TL;DR: Investigating the relationship between cerebral abnormalities detected by magnetic resonance imaging (MRI) and cognitive performance in nondemented outpatients with heart failure found MTA was related to cognitive dysfunction, involving memory impairment and executive dysfunction, whereas WMH wasrelated to depression and anxiety.
Abstract: Background/Aims: We purposed to investigate the relationship between cerebral abnormalities detected by magnetic resonance imaging (MRI) and cognitive performance in nondemented outpatients with heart failure (HF). Methods: In 58 patients with HF neuropsychological assessment was performed including tests of mental speed, executive functions, memory, language and visuospatial functions. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated on MRI of the brain. Correlations between MRI findings and the cognitive measures were calculated. Results: MTA correlated with memory (r = -0.353, p < 0.01), with executive functions (r = -0.383, p < 0.01) and the Mini Mental State Examination (r = -0.343, p < 0.05). Total WMH and deep WMH were found to correlate with depression and anxiety scores, but not with cognitive measures. Age, estimated premorbid intelligence and MTA were independent predictors of diminished cognitive performance. Conclusions: In HF patients, MTA was related to cognitive dysfunction, involving memory impairment and executive dysfunction, whereas WMH was related to depression and anxiety.
TL;DR: All MCI subtypes are at risk of converting to AD if the groups are carefully defined by an abnormal psychometric domain, and all subtypes except subjective memory loss converted to AD at higher than expected rates.
Abstract: Background/Aims: To evaluate baseline characteristics and conversion to dementia in mild cognitive impairment (MCI) subtypes. Methods: We prospectively evaluated
TL;DR: The prevalence of anxiety symptoms, depressive symptoms and comorbid anxiety and depressive symptoms seems to increase in the early phase of cognitive decline, and decreases as cognitive functioning further declines.
Abstract: Background/Aims: Anxiety and depression are common inpatients with cognitive decline and Alzheimer’s disease (AD), and recognition and treatment of these symptoms can improve their quality of life. The present study investigates anxiety and depression in different phases of cognitive decline. Methods: The sample consisted of five groups of elderly people in different phases of cognitive decline; four from a community-based sample (Longitudinal Aging Study Amsterdam), and one group of elderly people diagnosed with AD. ANOVAs were performed to investigate group differences in the severity and prevalence of anxiety and depression, and comorbid anxiety and depressive symptoms. Results: The prevalence rates of anxiety, comorbid anxiety and depressive symptoms and depressive symptoms follow a pattern of an increasing prevalence as cognitive performance declines and a decrease in the prevalence when cognitive functioning is severely impaired. AD patients report fewest anxiety symptoms. Conclusion: We found that the prevalence of anxiety symptoms, depressive symptoms and comorbid anxiety and depressive symptoms seems to increase in the early phase of cognitive decline, and decreases as cognitive functioning further declines. Elderly diagnosed with AD report less anxiety as expected, probably due to lack of insight caused by AD.
TL;DR: Galantamine appears to be an effective and safe therapy for patients with DLB.
Abstract: Background Dementia with Lewy bodies (DLB) is a common dementia of the elderly. A significant cholinergic deficit has been demonstrated that may be responsive to treatment by cholinesterase inhibitors (ChEIs). Methods A 24-week, open-label study was designed to assess the efficacy and safety of a ChEI, galantamine, in 50 patients with DLB. Results This study showed beneficial effects with galantamine in 2 of the 3 primary efficacy parameters. The scores on the Neuropsychiatric Inventory (NPI-12) improved by 8.24 points from baseline (p = 0.01) especially in visual hallucinations and nighttime behaviors (p = 0.004). The scores on the Clinician's Global Impression of Change improved by 0.5 points from baseline (p = 0.01). The third primary efficacy parameter, the Cognitive Drug Research Computerized Cognitive Assessment System, was unchanged from baseline. Adverse events were generally mild and transient. Conclusion Galantamine appears to be an effective and safe therapy for patients with DLB.
TL;DR: In this population of moderate and severe AD patients, treatment with memantine was associated with reducing worsening of clinical symptoms in AD during the 6-month study period.
Abstract: Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and delaying disease worsening is a relevant treatment outcome. Methods: Data from 6 randomized, double-blind, placebo-controlled, 6-month studies were pooled and a subgroup of patients (867 on placebo, 959 on memantine) with moderate to severe AD (Mini- Mental State Examination Results: More placebo-treated than memantine-treated patients showed any clinical worsening (28 vs. 18%; p Conclusion: In this population of moderate and severe AD patients, treatment with memantine was associated with reducing worsening of clinical symptoms in AD during the 6-month study period.
TL;DR: Depression in VAD was quantitatively and qualitatively different from that in AD regardless of the severity of dementia and gender; depression was more prevalent, severer and more retarded and vegetative in VaD than in AD.
Abstract: Background/Aims: To compare the prevalence and characteristics of depression in vascular dementia (VaD) and Alzheimer’s disease (AD) after adjusting for dementia severity and gender. Methods: One hundred and eight pairs of VaD and AD patients matched for dementia severity and gender were assessed. Results: Major depressive disorder (MDD) was more prevalent in the VaD group than in the AD group (20.4% in VaD, 10.2% in AD, p = 0.04, Cochran-MantelHaenszel, CMH, test) regardless of the dementia severity and gender. The odds ratio for developing MDD in the VaD group versus the AD group was estimated to be 2.20 (95% confidence interval = 1.02–4.74). Neurovegetative symptoms such as ‘felt tired and weak all the time’ (30.6% in VaD, 13.9% in AD, p = 0.003, CMH test) and ‘changed weight without trying’ (16.7% in VaD, 6.5% in AD, p = 0.02, CMH test) were more prevalent in the VaD group than in the AD group. Conclusion: Depression in VaD was quantitatively and qualitatively different from that in AD regardless of the severity of demen