Behaviour in frontotemporal dementia, Alzheimer's disease and vascular dementia

OBJECTIVES: The study aimed to increase understanding of behavioural changes in frontotemporal dementia (FTD) and identify features that best differentiate FTD from Alzheimer's disease (AD) and cerebrovascular dementia (CvD). METHODS: A semi-structured questionnaire was administered to carers of 30 FTD, 75 AD and 34 CvD patients. RESULTS: Behavioural changes that strongly discriminated FTD from AD and to a lesser extent CvD were loss of emotions and insight, selfishness, disinhibition, personal neglect, gluttony and sweet food preference, wandering, motor and verbal stereotypies, loss of pain, echolalia and mutism. Irritability, hyposexuality and hypersomnia did not discriminate. Emotional, eating and stereotyped behaviours correctly classified 95% of patients using regression analysis. CONCLUSIONS: Behavioural characteristics accurately differentiate FTD from AD and CvD. The findings highlight the particular importance of affective change in FTD, and underline the role of the frontotemporal lobes in emotion.     

Picture naming deficits in vascular dementia and Alzheimer's disease

Abstract

Picture naming deficits in Alzheimer's disease (AD) have been extensively studied but less is known about anomia in vascular dementia (VaD). We tested sources of anomia in these two dementia types by administering an extensive naming battery to 10 patients with VaD, 13 patients with probable AD, and 20 healthy age-and education-matched controls. Both dementia groups evidenced a semantic component in their anomia but the semantic deficit was more clearcut in the patients with AD than in the patients with VaD even though the groups were matched on dementia severity. Case-by-case analyses showed considerable performance variability but confirmed that when anomia is present, it commonly has a semantic component in both VaD and AD.     

Distinctive cognitive profiles in Alzheimer's disease and subcortical vascular dementia

BACKGROUND: There are inconsistencies in published reports regarding the profile of cognitive impairments in vascular dementia, and its differentiation from Alzheimer's disease. OBJECTIVES: To identify the overall profile of cognitive impairment in subcortical vascular dementia as compared with Alzheimer's disease; and the tests which best discriminate between these groups. METHODS: 57 subjects participated: 19 with subcortical vascular dementia, 19 with Alzheimer's disease, and 19 controls. The dementia groups were matched for age, education, and general levels of cognitive and everyday functioning. Subcortical vascular dementia was defined by clinical features (prominent vascular risk factors plus a previous history of transient ischaemic events or focal neurological signs) and substantial white matter pathology on magnetic resonance imaging. All subjects were given a battery of 33 tests assessing episodic and semantic memory, executive/attentional functioning, and visuospatial and perceptual skills. RESULTS: Despite a minimal degree of overall dementia, both patient groups had impairments in all cognitive domains. The Alzheimer patients were more impaired than those with vascular dementia on episodic memory, while the patients with vascular dementia were more impaired on semantic memory, executive/attentional functioning, and visuospatial and perceptual skills. Logistic regression analyses showed that the two groups could be discriminated with 89% accuracy on the basis of two tests, the WAIS logical memory--delayed recall test and a silhouette naming test. CONCLUSIONS: Subcortical vascular dementia and Alzheimer's disease produce distinctive profiles of cognitive impairment which can act as an adjunct to diagnosis. Many of the neuropsychological deficits thought to characterise Alzheimer's disease are also found in subcortical vascular dementia.     

Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia

OBJECTIVE: To explore the neuropsychiatric manifestations in patients with Alzheimer's disease (AD) and cortical and subcortical vascular dementia (VaD). METHODS: We investigated consecutive patients with dementia. All the participants received brain computed tomography. The diagnosis of dementia was confirmed by clinical criteria and the imaging findings. Only patients with probable AD, and subcortical and cortical VaD were included. The Mini Mental State Examination (MMSE) was used to evaluate global cognitive function, and the Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms. RESULTS: Of the 536 participants with dementia, 320 (59.7%) had AD, 161 (30%) had subcortical VaD, 35 (6.4%) had cortical VaD, and 16 (2.9%) had mixed cortical and subcortical VaD. Cortical VaD patients had the highest mean composite NPI scores in all domains and AD patients had the lowest composite scores in most domains. The mean composite scores of the apathy and sleep disturbance domains in patients with cortical VaD were significantly higher than those in the patients with AD after controlling for years of education and MMSE score (p < 0.01). CONCLUSIONS: There were few differences among the patients with AD, subcortical VaD and cortical VaD. The most consistent differences were the high sleep disturbance scores in those with cortical VaD.     

Cerebrospinal fluid pyruvate levels in Alzheimer's disease and vascular dementia

Increased amounts of CSF pyruvate and lactate were found in patients with AD and patients with vascular dementia (VaD). In the AD group, CSF pyruvate values did not show any overlap with those obtained in controls; within the VaD group, the highest values were observed in possible VaD cases. A significant correlation between the severity of dementia and these biochemical parameters was also observed in both AD and possible VaD. The similarities of CSF pyruvate patterns observed in AD and possible VaD patients implicate a neurodegenerative component in this VaD subgroup.     

Neuropsychological differentiation of Alzheimer's disease from vascular dementia

The purpose of this study was to determine whether cognitive test performances alone could distinguish patients with probable Alzheimer's disease from those with probable vascular dementia. Sixty-eight outpatients with clinical diagnoses of either Alzheimer's disease or vascular dementia were administered a brief battery of neuropsychological tests. Scores from the Boston Naming Test and the Hopkins Verbal Learning Test were identified as most discriminating of the groups. Seventy-seven per cent of the sample was correctly classified by a stepwise discriminant function analysis. Results of this study indicate that selected neuropsychological tests have moderate concurrent utility in the differential diagnosis of dementia.     

Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia

Background/Aims:

The aim of the following study is to compare the behavioral and psychological symptoms of dementia (BPSD) in patients of Alzheimer disease (AD) and vascular dementia (VaD).

Materials and Methods:

We used National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer''s Disease and Related Disorders Association criteria for diagnosing AD and National Institute of Neurological Disorders and Stroke-Association International pour la Recherche et l’Enseignement en Neurosciences Criteria for diagnosing VaD. VaD cohort was further subcategorized into small vessel and large vessel disease. The severity of cognitive impairment and the BPSD were studied by means of the Clinical Dementia Rating Scale (CDR) and the Neuropsychiatric Inventory respectively.

Results:

We studied 50 AD and 50 VaD patients of whom 38 were small vessels and 12 were large vessels VaD. The severity of dementia was comparable in both groups. The agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, irritability, aberrant motor behavior, appetite and eating behavior and night-time behaviors occurred significantly more frequently in patients with VaD than AD. We found a weak positive correlation between the CDR score and the number of neuropsychiatric symptoms per patient in both cohorts. Elation/euphoria, agitation/aggression was significantly more frequent in patients with large vessel in comparison to small vessel VaD.

Conclusions:

BPSD are common in both types of dementia and they are more severe in VaD than AD when the groups have similar levels of cognitive impairment.     

Local and systemic GM-CSF increase in Alzheimer's disease and vascular dementia

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of brain damage in dementia. The aim of the present study was to investigate patterns of local and systemic cytokine release in patients with Alzheimer's disease (AD) and vascular dementia (VAD). The intrathecal levels of cytokines were related to neuronal damage and cerebral apoptosis. Twenty patients with early AD and 26 patients with VAD were analyzed with respect to cerebrospinal fluid (CSF) and serum levels of pro- and anti-inflammatory cytokines. In addition, CSF levels of Fas/APO-1 and bcl-2, a measure for apoptosis, and Tau protein, a marker for neuronal degradation, were studied. Significantly increased CSF levels of GM-CSF but not of other cytokines were observed in both dementia groups. These patients displayed a significant correlation between the GM-CSF levels and the levels of Fas/APO-1 and Tau protein in CSF. Our study demonstrates an intrathecal production of GM-CSF, a cytokine stimulating microglial cell growth and exerting inflammatogenic properties. It is suggested that GM-CSF once secreted induces programmed cell death in the brain tissue of patients with dementia.     

Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease, and vascular dementia

BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in the major dementias, particularly dementia with Lewy bodies (DLB), where it is one of three core clinical diagnostic features. OBJECTIVES: To examine the frequency, characteristics, and diagnostic utility of FC in dementia using clinical, attentional, and EEG markers. Method:- A total of 155 subjects (61 with AD, 37 with DLB, 22 with vascular dementia [VaD], 35 elderly controls) received clinical evaluation for FC using a semiquantified measure applied by experienced clinicians and 90-second cognitive choice reaction time (CRT) and vigilance reaction time (VIGRT) trials. Forty subjects also received an evaluation of mean EEG frequency across 90 seconds. RESULTS: Patients with DLB had a greater prevalence and severity of FC than did patients with AD or VaD rated using clinical, attentional, and EEG measures. The 90-second cognitive and EEG trials demonstrated that FC occurs on a second-to-second basis in patients with DLB. Patients with VaD had a higher prevalence of FC than did those with AD, although the profile of FC was different from that expressed by DLB cases. Optimal cutoff values on the clinical scale achieved good discrimination between the dementia groups (sensitivity 81%, specificity 92%, DLB versus AD; sensitivity 81%, specificity 82%, DLB versus VaD; sensitivity 64%, specificity 77%, VaD versus AD). CONCLUSION: Standardized assessment methods demonstrate that FC is significantly more common and severe in DLB than in other major dementias. The periodicity of FC is different in DLB and VaD cases, with important implications for the underlying causal mechanisms and for differential diagnosis.     

Preclinical cognitive trajectories differ for Alzheimer's disease and vascular dementia

We investigated differences between Alzheimer's disease (AD) and vascular dementia (VaD) from the appearance of the first cognitive symptoms, focusing on both time of onset and rate of accelerated decline for different cognitive functions before dementia diagnosis. Data from a longitudinal population-based study were used, including 914 participants (mean age = 82.0 years, SD = 5.0) tested with a cognitive battery (word recall and recognition, Block Design, category fluency, clock reading) on up to four occasions spanning 10 years. We fit a series of linear mixed effects models with a change point to the cognitive data, contrasting each dementia group to a control group. Significant age-related decline was observed for all five cognitive tasks. Relative to time of diagnosis, the preclinical AD persons deviated from the normal aging curve earlier (up to 9 years) compared to the preclinical VaD persons (up to 6 years). However, once the preclinical VaD persons started to decline, they deteriorated at a faster rate than the preclinical AD persons. The results have important implications for identifying the two dementia disorders at an early stage and for selecting cognitive tasks to evaluate treatment effects for persons at risk of developing AD and VaD.     

1H-MRS evaluation of metabolism in Alzheimer's disease and vascular dementia

Proton magnetic resonance spectroscopy (1H-MRS) allows major metabolites to be measured noninvasively in defined regions of the living brain, and can detect biochemical abnormalities where conventional structural imaging appears normal. MRS can be performed in 10 min as part of a clinical MRI examination. Biochemical abnormalities in Alzheimer's Disease (AD), vascular dementia (VaD) and other primary degenerative dementias have been investigated using MRS. Characteristic and consistent abnormalities in AD are decreased N-acetyl aspartate (NAA) and elevated myo-inositol (mI) in the mesial temporal and parieto-occipital cortex. These are thought to represent neuronal loss/dysfunction and gliosis, in anatomic distributions which reflect early pathological involvement and atrophy patterns in AD. Less consistent disturbances of glutamine and glutamate (Glx) and choline-containing compounds (Cho) have also been reported. Similar changes are seen in VaD; mostly in white matter, whereas in AD they predominate in cortical grey matter. The regional distribution of grey matter involvement may differ between AD and other degenerative dementias. Hence, both the nature and anatomic distribution of metabolite abnormalities contribute to diagnostic discrimination with MRS. NAA/mI ratios from short echo time spectra of the posterior cingulate region cortex discriminate reliably between AD subjects, normal individuals and those with VaD, and provides a useful clinical test, as an adjunct to structural imaging. Elevated mI is detected in mild cognitive impairment (MCI) and quantitative metabolite measures correlate with degrees of cognitive impairment in AD; these suggest a possible role for MRS in early diagnosis and for surrogate biochemical markers for monitoring disease progression and therapeutic response.     

Qualitative analyses of clock drawings in Alzheimer's disease and vascular dementia

Although quantitative analyses of clock drawings (CD) have achieved widespread clinical use as a cognitive screening, little is known about the qualitative profiles of CD in Alzheimer's disease (AD) and vascular dementia (VD). To address this issue, the present study examined the significance of qualitative analyses of CD in AD and VD. Sixty-seven AD patients, 44 VD patients and eight controls underwent a clock drawing test and took the Mini-Mental State Examinations (MMSE). In the dementia groups, quantitative scores significantly decreased compared with controls and were significantly correlated with MMSE scores. Qualitative analysis demonstrated that in AD patients qualitative error patterns were stable and independent of severity. In contrast, in VD patients the frequency of graphic difficulties and conceptual deficit increased, while the frequency of spatial and/or planning deficit decreased, as severity worsened. In mild dementia groups the frequency of spatial and/or planning deficit was significantly higher in VD. In moderate dementia groups, the frequency of graphic difficulties was significantly higher in VD and the difference in the frequency of spatial and/or planning deficit seen in mild dementia disappeared. The present study suggests that qualitative analyses of clock drawings could demonstrate the neuropsychological profiles of AD and VD and their differences between these dementias.     

Intrathecal release of nitric oxide in Alzheimer's disease and vascular dementia

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of brain damage in dementia. We have recently demonstrated that patients with Alzheimer's disease (AD) and vascular dementia (VaD) display an intrathecal production of proinflammatory cytokines. TNF-alpha, one of these cytokines, leads to the production of nitric oxide (NO), a potent inflammatory mediator, by induction of inducible NO synthase. The aim of the present study was to investigate the intrathecal levels of nitrate, one of the main metabolites of NO, and to relate its levels to the degree of intellectual impairment, in patients with AD and VaD. Twenty patients with early AD and 26 patients with VaD were analyzed with respect to cerebrospinal fluid levels of nitrate by gas chromatography/mass spectrometry. Interestingly, in patients with AD but not VaD, the intrathecal levels of nitrate were significantly and inversely correlated (r = -0.68, p = 0.002) to the degree of intellectual impairment. Our study demonstrates an inverse correlation between the intrathecal levels of nitrate and the degree of cognitive impairment in patients with AD, suggesting a neuroprotective effect of NO in AD.     

Cytokines in Alzheimer's disease.

1. Human astrocytoma cells produced biologically active interleukin-6 when treated with a variety of agents including bacterial lipopolysaccharides, viruses, and interleukin-1. 2. Both human recombinant IL-6 and IL-6 produced by stimulated astrocytes promoted differentiation of cultured neuronal cells and reduced survival time in culture. 3. Interleukin-6 and interleukin-1 stimulated the synthesis of the Alzheimer's disease beta-amyloid precursor protein. 4. Cytokines may be involved in stimulation of dystrophic neuritic sprouting, neuronal death, and amyloid deposition noted in the brains of Alzheimer's disease patients.     

Neuropsychiatric symptoms and functional status in Alzheimer's disease and vascular dementia patients

Neuropsychiatric symptoms (NPS) are increasingly recognized as common in patients with dementia, both of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). In this study, 302 demented patients, 166 with AD and 136 with VaD, were evaluated for NPS according to the Neuropsychiatric Inventory (NPI) score at the Alzheimer's Evaluation Unit of Casa Sollievo della Sofferenza Hospital-IRCCS, San Giovanni Rotondo, Italy. A comprehensive geriatric assessment was also performed in all demented patients. The means of NPI scores did not differ in two groups. The overall prevalence of NPS was similar in both groups of patients (69.7% vs. 69.4%). Patients with AD had higher frequency in agitation/aggression and irritability/lability than VaD patients. Logistic analysis demonstrated a significant association between severity of the cognitive impairment and depression and eating disorders in both AD and VaD patients. The association with agitation/aggression, irritability/lability, and aberrant motor activity was found in AD only, and with apathy in VaD patients only. In both AD and VaD patients, there was a significant association between the impairment in activities of daily living (ADL) and the majority of NPI domains. A significant association was also found between the impairment of the instrumental activities of daily living (IADL) and agitation/aggression, anxiety, aberrant motor activity in AD and depression, apathy, irritability/lability, sleep disturbance and eating disorders in both AD and VaD patients. In particular, a causal mediation analysis was performed to better understand whether the relationship of NPS to functional impairment was direct or mediated by severity of cognitive dysfunction, i.e., Clinical dementia rating scale (CDR) score. Only agitation/aggression was mediated by the CDR score in affecting ADL status in VaD patients (OR: 1.12, 95% CI: 1.01-1.27). The NPI-Distress scores showed a significantly higher levels of distress in caregivers of AD than VaD. There were significant differences between AD and VaD patients with NPS, and these symptoms varied according to dementia subtype and severity and induced marked disability in ADL and IADL, increasing, prevalently, the distress of the caregivers of AD patients.     

Estrogen receptor gene polymorphisms in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia

The association between the estrogen receptor (ER-alpha) gene and dementia was examined in 223 patients with Alzheimer's disease (AD), 66 with vascular dementia (VD), 17 with alcohol-associated dementia (ALD) and 134 healthy elderly control subjects. The PvuII and XbaI restriction fragment length polymorphisms of the ER-alpha gene were represented as Pp (PvuII) and Xx (XbaI), with capital letters signifying the absence of restriction sites and small letters the presence of restriction sites. We found that the frequency of the ER-alpha gene P allele and X allele in the late-onset AD (LOAD) group (P allele was 0.51, X allele was 0.30) was significantly higher than that in controls (P 0.38, p < 0.01; X 0.20, p < 0.01), and that the frequency of the ER-alpha gene P allele and PP genotype was significantly different between apolipoprotein E epsilon4 carriers and noncarriers in LOAD. These findings suggest that the genotype of the ER-alpha gene may be specific in LOAD, and that the ER-alpha gene was an additional risk for LOAD.