Showing papers in "Dementia and Geriatric Cognitive Disorders in 2003"
TL;DR: The aim of this study was to detect behavioral subsyndromes of the 12-item Neuropsychiatric Inventory (NPI) in patients with dementia living in the community, and found the presence of mood/apathy, psychosis, and hyperactivity.
Abstract: The aim of this study was to detect behavioral subsyndromes of the 12-item Neuropsychiatric Inventory (NPI). Cross-sectional data of 199 patients with dementia living in the community were collected. Principal component analysis (with Varimax rotation) was used for factor analysis. Results showed the presence of three behavioral subsyndromes: mood/apathy, psychosis, and hyperactivity. Anxiety was regarded as a separate symptom. The subsyndrome mood/apathy was the most common, occurring in almost 80% of the patients, versus psychosis and hyperactivity, which occurred in 37 and 60% of the patients, respectively.
248 citations
TL;DR: The uniquely profound visual-perceptual and attentional-executive impairments that characterize DLB are consistent with the most frequent locations of Lewy bodies in frontal, cingulate, and inferior temporal cortex and may be related to the characteristic visual hallucinations and clinical fluctuations of this disease.
Abstract: To resolve differences in the literature, we have systematically reviewed 21 controlled comparisons of the cognitive performance of patients with dementia with Lewy bodies (DLB) These were identified by end May 2002 by Medline and PsycInfo searches, checking reference lists and contacting authors. Nine had comparisons between DLB patients (total n = 180) and age-matched controls (n = 172). Sixteen had comparisons between DLB (n = 312) and Alzheimer's disease (AD, n = 380). Three compared DLB (n = 48) with Parkinson's disease (PD, n = 65). Two raters independently scored the methodological quality. This was variable with a lack of high-quality studies (median rating 3 on a 0-7 scale, Kw = 0.41). There was a significant heterogeneity in results with marked discrepancies between studies. In a meta-analysis, DLB patients were more cognitively impaired than were AD or PD patients (95% CI of inverse variance weighted average of effect size relative to controls DLB 2.0-2.2; AD 1.4-1.6; PD 0.7-1.0). To permit an analysis of impairments in specific cognitive areas, the cognitive abilities underpinning the wide variety of tasks used were classified by a group of experienced neuropsychologists. Reducing overlapping task classifications using factor analysis showed large effect sizes relative to controls, AD and PD on two factors (combined variance 30%): attentional/executive impairment (effect sizes 1.1-2.9) and visual-perceptual impairment (0.7-3.6). There were small differences on two other factors (combined variance 39%): general verbal/non-verbal impairment (-0.12 to -0.5) and relative verbal memory impairment (-0.33 to 0.21). The cognitive performance is also more variable in DLB than in controls or in AD, but not PD (ratio of DLB to comparator standard deviations estimated from linear regression: DLB/controls 2.5-3.6; DLB/AD 2.1-2.6; DLB/PD 0.8-1.0). The greater variability of patients with DLB is seen only on tasks needing timed or motor responses, visual learning, executive or attentional abilities, or with visual content. Further stratification indicated that recent consensus diagnostic criteria, clinical diagnoses, and milder dementia were all associated with a more distinctive cognitive profile. The uniquely profound visual-perceptual and attentional-executive impairments that characterize DLB are consistent with the most frequent locations of Lewy bodies in frontal, cingulate, and inferior temporal cortex and may be related to the characteristic visual hallucinations and clinical fluctuations of this disease. These findings need to be confirmed in prospective, longitudinal, clinicopathological studies.
210 citations
TL;DR: The neuropsychological profile of PD patients without dementia was compared with a control group consisting of 38 healthy elderly subjects, and subjects with mild cognitive impairment were older, had a later onset of the disease, and more severe motor symptoms than cognitively intact subjects.
Abstract: Cognitive deficits are often associated with Parkinson's disease (PD), although their prevalence in PD patients without dementia is still unknown. In order to describe the neuropsychological profile of PD patients without dementia, a sample of 103 PD patients was compared with a control group consisting of 38 healthy elderly subjects. Psychometric assessment consisted of the Mini Mental State Examination, the Dementia Rating Scale and a battery of neuropsychological tests. The Beck Depression Inventory was used to assess depression in PD patients. Dementia was diagnosed in 27 patients. Among non-demented subjects, 34 (45%) had no cognitive impairment and 42 (55%) had a mild cognitive impairment. Subjects with mild cognitive impairment were older, had a later onset of the disease, and more severe motor symptoms than cognitively intact subjects. Identification of mild cognitive impairment is important, since these symptoms are important for patient management and may also facilitate to determine prognosis.
205 citations
TL;DR: This study suggests that low CSF-Aβ42 is found also in an unselected population-based sample of old demented patients and provides the first evidence of a disturbance in the metabolism of Aβ, specifically involving Aβ42, before the onset of clinical symptoms in AD.
Abstract: Deposition of β-amyloid (Aβ) is an early pathogenic event in Alzheimer’s disease (AD). We measured Aβ42 and Aβ40 in cerebrospinal fluid (CSF) in a population-based sample of 85-year-olds, 27 demented
193 citations
TL;DR: There is good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.
Abstract: It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer's disease (AD). We measured the levels of alpha(1)-antichymotrypsin (ACT), alpha(1)-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.
159 citations
TL;DR: Kinematic handwriting analysis was used to quantify differences in fine hand motor function in patients with probable AD and mild cognitive impairment (MCI, as an assumed initial stage of AD) compared to depressed patients and healthy controls.
Abstract: A variety of studies have demonstrated that motor disorders, parkinsonism and extrapyramidal motor symptoms (EPMS) are common in patients with Alzheimer’s disease (AD). Several studies have reported an association of EPMS with severity, progression and poor prognosis of AD. The majority of these studies used clinical assessments for the rating of EPMS. In this study, kinematic handwriting analysis was used to quantify differences in fine hand motor function in patients with probable AD and mild cognitive impairment (MCI, as an assumed initial stage of AD) compared to depressed patients and healthy controls. Both patients with MCI and patients with probable AD exhibited loss of fine motor performance. Movements of AD patients were significantly less regular than those of healthy controls.
136 citations
TL;DR: The role of dopamine in the modulation of the WM function in PD patients is highlighted as L-dopa administration had a ameliorative effect on accuracy and reaction times in both visual-spatial and visual-object tasks.
Abstract: Visual-spatial working memory (WM) impairment is frequently associated with the early stage of Parkinson's disease (PD). The aim of this study was to evaluate the performance of a group of PD patients in visual-spatial and visual-object WM tasks and to investigate the effect of administering the dopaminergic agonist apomorphine (experiment 1) or the dopamine precursor L-dopa (experiment 2) on the performance of tests assessing these functions. To study WM processes, the PD patients and age-matched normal controls were given an n-back task paradigm. In both experiments, the PD patients were submitted to two evaluations: one after a 12-hour therapy washout and the other 15 min after a subcutaneous infusion of apomorphine (average 0.04 mg/kg) or 20/30 min after L-dopa intake (200 mg p.o.). The apomorphine infusion had a worsening effect on reaction times in both visual-spatial and visual-object WM tasks, but it did not influence performance accuracy. Instead, L-dopa administration had a ameliorative effect on accuracy and reaction times in both visual-spatial and visual-object tasks. These results highlight the role of dopamine in the modulation of the WM function in PD patients.
122 citations
TL;DR: The positive effects on the efficacy outcome measures combined with no additional costs from a societal perspective indicate that donepezil is a cost-effective treatment, representing an improved strategy for the management of patients with AD.
Abstract: The costs and consequences of donepezil versus placebo treatment in patients with mild to moderate Alzheimer's disease (AD) were evaluated as part of a 1-year prospective, double-blind, randomized, multinational clinical trial. Patients received either donepezil (n = 142; 5 mg/day for 28 days followed by 10 mg/day according to the clinician's judgement) or placebo (n = 144). Unit costs were assessed in 1999 Swedish kronas (SEK) and converted to US dollars (USD). Donepezil-treated patients gained functional benefits relative to placebo on the Progressive Deterioration Scale (p = 0.042) and Instrumental Activities of Daily Living scale (p = 0.025) at week 52. Caregivers of donepezil-treated patients spent an average of 400 h less annually providing care than caregivers of placebo-treated patients. Mean annual healthcare costs were SEK 137,752 (USD 16,438) per patient for the donepezil group and SEK 135,314 (USD 16,147) in the placebo group. With the average annual cost of donepezil at SEK 10,723 (USD 1,280) per patient, the SEK 2,438 (USD 291) cost difference represented a 77% cost offset. When caregiver time and healthcare costs were included, mean annual costs were SEK 209,244 (USD 24,969) per patient in the donepezil group and SEK 218,434 (USD 26,066) in the placebo group, a total saving associated with donepezil treatment of SEK 9,190 (USD 1,097) per patient [95% CI of SEK -43,959 (USD -5,246), SEK 25,581 (USD 3,053); p = 0.6]. The positive effects on the efficacy outcome measures combined with no additional costs from a societal perspective indicate that donepezil is a cost-effective treatment, representing an improved strategy for the management of patients with AD.
108 citations
TL;DR: The results suggest that simvastatin acts directly on the processing of APP by inhibiting both the α- and the β-secretase pathways.
Abstract: We investigated the clinical and biological effects of cholesterol-lowering treatment with a statin in 19 patients with Alzheimer’s disease. They received simvastatin 20 mg/day for 12 weeks in an open
103 citations
TL;DR: An overview will be presented of music therapy, art therapy, movement therapy and reminiscence therapy, memory training, reality orientation, validation therapy, self-maintenance therapy, behaviour therapy, milieu therapy and staff training.
Abstract: An overview will be presented of music therapy, art therapy, movement therapy and reminiscence therapy, memory training, reality orientation, validation therapy, self-maintenance therapy, behaviour therapy, milieu therapy and staff training. The overview will examine the aims of each, the principles on which procedures are based and the proof of their effectiveness. The principal aim of non-drug therapies is to influence symptomatic dementia beneficially and to improve the abilities remaining to the patient. The potential benefits are usually deduced from studies made without control groups. At the present time, proof of the effectiveness of these therapies is still lacking as controlled, randomized studies have yet to be conducted, and so a fundamental evaluation of the therapeutic benefits of non-drug therapies in the treatment of dementia cannot yet be made.
101 citations
TL;DR: Results indicate that the executive and attentional dysfunctions associated with PD and DLB are unlikely to be a direct and specific consequence of caudate atrophy as assessed on MRI.
Abstract: Objective: To compare whole brain and caudate volume on MRI in subjects with Parkinson’s disease without cognitive impairment (PD), Parkinson’s disease with dementia with Lewy bodie
TL;DR: The concentration of plasma total homocysteine is increased in AD patients and may be associated with the T/T genotype in the MTHFR gene; however, the distribution of the M THRF C677T polymorphism in the Polish population does not differ in AD and controls.
Abstract: Background: Alzheimer’s disease (AD) is the most common dementia disorder in elderly people. Currently, the only known genetic factor associated with the development of sporadic AD
TL;DR: When treated with a vitamin B12-B6-folate combination, patients with mild cognitive impairment and hyperhomocysteinaemia appear to improve their blood-brain barrier function and may also stabilise their cognitive status.
Abstract: Thirty patients had mild cognitive impairment and increased homocysteine levels in serum. On average, they were supplemented orally with a high dose of a vitamin B12-B6-folate combination for 270 days. All patients had normal serum B12 and folate levels at baseline. Cerebrospinal fluid levels of the tau protein (CSF-tau) and the albumin ratio were measured before and after treatment. The serum homocysteine levels were normalised after treatment. The albumin ratio significantly correlated with vascular risk factors. At baseline, the ratio was higher in the patients in comparison with age-matched controls. After treatment, the ratio was significantly reduced, which may indicate a tightening of the blood-brain barrier. The CSF-tau levels did not change significantly although there was a numeric decline. None of the patients progressed into dementia during the treatment period. When treated with a vitamin B12-B6-folate combination, patients with mild cognitive impairment and hyperhomocysteinaemia appear to improve their blood-brain barrier function. They may also stabilise their cognitive status. Further investigations are warranted on the role of blood-brain barrier dysfunction in the pathogenesis of dementia.
TL;DR: FTD patients reveal a different pattern of qEEG changes than AD patients, which demonstrates the importance ofqEEG for FTD diagnosis and indicates Cognition is selectively better in FTD than in AD.
Abstract: Objective: To investigate the relationship between quantitative EEG (qEEG) measurements in frontotemporal dementia (FTD), Alzheimer’s disease (AD) and healthy controls and to study
TL;DR: Impairments of cognitive processing speed, working memory and executive functions are frequent in elderly stroke patients without dementia and represent the main cognitive components of early cognitive impairments.
Abstract: Background: Few studies have examined the profile of cognitive impairments in older stroke patients without dementia. Method: A standardized evaluation including
TL;DR: The newest DSM-IV classification found more cases of delirium especially among acutely ill, hospitalized patients, and the largest number of patients not overlapping with any other diagnostic group.
Abstract: A cross-sectional study was performed to evaluate the concordance of the present criteria of delirium among elderly (>70 years) geriatric hospital patients (n = 230) and nursing home residents (n = 195). Different subjects were diagnosed as having delirium when operationalized criteria according to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III, DSM-III-R, DSM-IV) and the World Health Organization's International Classification of Diseases (ICD-10) were used. Whereas 132 subjects (31.1%) met the criteria for delirium by at least 1 classification, only 25 (5.9%) met all 4. The most inclusive was the DSM-IV (24.9% of the subjects) followed by DSM-III-R (19.5%), DSM-III (18.8%) and ICD-10 (10.1%), respectively. The DSM-IV and ICD-10 had the largest number of patients not overlapping with any other diagnostic group. The newest DSM-IV classification found more cases of delirium especially among acutely ill, hospitalized patients.
TL;DR: Investigation of the validity and reliability of the clinical criteria using a computerized ‘dementia diagnosis system’ for each of 6 sets of criteria concluded that the forced use of decision trees through aComputerized system enhances the accuracy of theclinical diagnoses of dementia.
Abstract: Data from 204 participants from the Oxford Project to Investigate Memory and Ageing, who were diagnosed post-mortem using the histopathological criteria of the Consortium to Establish a Registry for A
TL;DR: The RDST is a new psychometric screening tool to support the diagnosis of dementia that includes a word generation task and a number transcoding task and can be interpreted as age-appropriate or below average with good sensitivity and specificity.
Abstract: The Rapid Dementia Screening Test (RDST) is a new psychometric screening tool to support the diagnosis of dementia. It includes two parts – a word generation task and a number transcoding task; it is
TL;DR: Estimates of the total glial cell population in 14 AD cases and 20 controls to determine whether brains from AD patients have a different number of neocortical glial cells than controls were obtained.
Abstract: Most studies agree that specific regions of the hippocampus and specific subcortical regions show neuronal loss in Alzheimer’s disease (AD). The aim of the study was to use design-based stereological
TL;DR: SMI was weakly associated with previous cognitive decline and was not associated with APOE e4, and cognitive impairment was most strongly associated in urban residents, particularly rural-to-urban migrants.
Abstract: Correlates of subjective memory impairment (SMI) were investigated using data from a community study of 1,204 individuals aged 65 or over in an urban and rural area of South Korea. SMI and depression were ascertained from the Geriatric Mental State Schedule and cognitive function from the Korean version of the Mini-Mental State Examination (MMSE-K). 686 participants had also completed the MMSE-K two years earlier. SMI was present in 22% of the sample and was associated with depression and lower MMSE-K scores. Depression and SMI were most strongly associated in the presence of cognitive impairment. SMI was weakly associated with previous cognitive decline and was not associated with APOE e4. SMI and cognitive impairment were most strongly associated in urban residents, particularly rural-to-urban migrants.
TL;DR: It is suggested that the many mWCST scores could be reduced to three major factors, and that the perseveration score may effectively represent an aspect of executive dysfunction in AD and MCI patients.
Abstract: In order to explore the factor structure of a modified version of the Wisconsin Card Sorting Test (mWCST) and to identify the dimensions of deficit in patients with Alzheimer’s disease (AD) and mild c
TL;DR: Evidence is provided that high tHcy levels are associated with cognitive impairment, in particular that of frontal-executive function, and must receive greater attention as a risk factor for cognitive impairment.
Abstract: Background: Elevated total homocysteine (tHcy) levels are associated with an increased risk of cerebrovascular disease. It is uncertain whether tHcy is also an independent risk fact
TL;DR: Evidence is provided that dementia per se, independently from physical disability, is a strong predictor of death in the elderly, in a population-based study carried out in Italy.
Abstract: Dementia is known to be associated with excess mortality. Physical disability, as a marker of dementia severity, is often considered the last step on the way from disease to death. The objective of th
TL;DR: It is concluded that atrophy of the substantia innominata on MRI helps to predict response to donepezil treatment in patients with Alzheimer’s disease.
Abstract: To investigate whether atrophy of the substantia innominata as shown on magnetic resonance imaging (MRI), reflecting degeneration of cholinergic neurons in the nucleus basalis of Meynert, predicts response to donepezil treatment in patients with Alzheimer's disease (AD), we studied correlations between the thickness of the substantia innominata and clinical efficacy Eighty-two patients were divided into responders, including transiently and continuously responding groups, and nonresponders, based on the changes in the Mini-Mental State Examination (MMSE) score from baseline at 3 months and at 12 months Atrophy of the substantia innominata was more pronounced in transiently and continuously responding groups than nonresponders, but no significant change in the thickness between transiently and continuously responding groups was found The MMSE score changes from baseline at 3 months and at 12 months significantly inversely correlated with the thickness of the substantia innominata Logistic regression analysis revealed that the overall discrimination rate with the thickness of the substantia innominata was 70% between responders and nonresponders We conclude that atrophy of the substantia innominata on MRI helps to predict response to donepezil treatment in patients with AD
TL;DR: In conclusion, galantamine offered sustained efficacy to patients with ‘advanced moderate’ AD, confirming the benefits seen in published studies of patients with mild-to-moderate AD and has potential for broader use in clinical practice.
Abstract: Galantamine (Reminyl®), a novel agent with a dual mode of action, modulates nicotinic acetylcholine receptors and inhibits acetylcholinesterase. Galantamine has consistently demonstrated a
TL;DR: Since verbs are supposed to be more demanding of executive resources than nouns, a higher sensitivity to verbs should be expected in any brain pathology, but mostly in FTD in which executive resources are typically reduced.
Abstract: Object and action naming and comprehension were tested in frontotemporal dementia (frontal variant, FTD), in Alzheimer's disease (AD) and in controls. Although lower scores were obtained by all groups, we can confirm that actions were proportionally more impaired in FTD. The correlation between action naming deficit and severity of dementia was stronger in this group than in AD. The correlation analysis also suggested that the naming disorder was different in nature in FTD (mostly a dysexecutive deficit) and in AD (mostly a linguistic disorder). Our explanation is that since verbs are supposed to be more demanding of executive resources than nouns, a higher sensitivity to verbs should be expected in any brain pathology, but mostly in FTD in which executive resources are typically reduced.
TL;DR: Results suggest that frontal function, as assessed by SPECT, affects the patient’s response to treatment with donepezil, and may aid in the selection of possible treatment responders.
Abstract: We attempted to identify the characteristic patterns in regional cerebral blood flow (rCBF) of patients with Alzheimer's disease who responded to donepezil therapy. Sixty-one patients treated with donepezil were divided into two groups (responders and nonresponders) on the basis of changes in their Mini Mental State Examination (MMSE) scores from baseline to study endpoint. We analyzed single-photon emission computed tomography data (SPECT) at baseline using three-dimensional stereotactic surface projections and compared differences in rCBF between the two groups. Statistical maps showed a significantly lower rCBF of the lateral and medial frontal lobes in the nonresponders than in the responders. There was a significant inverse correlation between the relative rCBF reduction in the frontal lobe and the MMSE change. These results suggest that frontal function, as assessed by SPECT, affects the patient's response to treatment with donepezil. Measuring rCBF may aid in the selection of possible treatment responders.
TL;DR: The data show that the mutant H63D allele potentially interacts with the ApoE Ε4 allele to significantly reduce age at onset of AD compared to Apolipoprotein E (ApoE) Ε 4 carriers alone, but has no effect on age at start of AD in ApOE ε4 non-carriers.
Abstract: The H63D mutation in the hemochromatosis gene (HFE) has recently been considered as a risk factor in Alzheimer`s disease (AD) with advancing age at onset of the disease, independently of the apolipopr
TL;DR: Attentional and executive impairments are underpinned by WMH in fronto-striato-thalamo-frontal circuits inFrontal atrophy is identified as a novel substrate of cognitive decline in stroke patients.
Abstract: Aim: The current study determines the MRI correlations of the early neuropsychological post-stroke cognitive deficits. Method: Detailed neuropsychological assessments (attention and working memory) were undertaken in 50 stroke survivors >75 years of age [38 with ageing-associated cognitive decline (AACD)] and 15 age-matched controls. A 1.5-tesla General Electric MRI scanner was used. Standardized visual ratings were undertaken of white matter hyperintensities (WMH). Grey matter volumes were assessed using voxel-based morphometery. Results: Associations were identified between processing speed and executive function and the severity of WMH in key areas. In addition, atrophy in the fronto-subcortical circuits was associated with AACD. Conclusion: Attentional and executive impairments are underpinned by WMH in fronto-striato-thalamo-frontal circuits. Frontal atrophy is identified as a novel substrate of cognitive decline in stroke patients.
TL;DR: The Short Cognitive Evaluation Battery appears to be a highly sensitive and specific tool for discriminating between patients with mild AD and healthy elderly individuals and in combination with clinical evaluation, the SCEB could improve the specificity of the difficult discrimination between mildAD and depression.
Abstract: Because Alzheimer’s disease (AD) tends to be underdiagnosed, there is an increasing need for accurate neuropsychological screening tools that are easy to administer by general practitioners or special