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.     

Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia

The prevalence of Alzheimer's disease (AD) and vascular dementia (VAD) increases with aging of the population. The role of lipoproteins in the pathogenesis of AD is unclear: apoE₂ offers protection and apoE₃ is neutral, while apoE₄ promotes the development of the disease. Recently, several studies have confirmed the role of oxidative stress in the pathogenesis of AD and VAD. HDL-associated paraoxonase is one of the antioxidative enzymes that may reduce LDL oxidation. In our study, we investigated the lipid parameters of the sera and the serum paraoxonase activity in patients with AD and VAD. Lipid parameters were determined by an autoanalyzer in 30 AD patients, 40 VAD patients and 40 healthy, age-matched control (C) subjects. Paraoxonase activity was measured spectrophotometrically using paraoxon as the substrate. The phenotypic distribution of paraoxonase was determined by the dual substrate method, using paraoxon and phenylacetate as substrates. In our results, we found that most of the patients with AD had the apoE4 isoform, consistent with other studies. In the VAD and AD patients we found significantly higher total-cholesterol compared to the control group (C: 4.71 ± 0.89, VAD: 6.3 ± 0.8, AD: 6.52 ± 0.7 mmol/l; p < 0.01) and LDL-cholesterol levels (C: 2.6 ± 0.6, VAD: 3.96 ± 0.8, AD: 3.84 ± 0.6 mmol/l; p < 0.001). The HDL-associated antioxidant, paraoxonase activity did not differ significantly in the patient groups, but compared to the healthy control subjects, paraoxonase activity was significantly lower in both of the patient groups (C: 188 ± 55 U/l; AD: 131 ± 37, VAD: 151 ± 50 l; p < 0.05). Our results suggest that the defect in HDL-associated antioxidant capacity plays a role in the pathogenesis of Alzheimer's disease and vascular dementia. Received: 30 November 2001 / Accepted: 24 January 2002     

Olfactory dysfunction in dementia of Alzheimer's type and vascular dementia

Background: Olfactory function in vascular dementia has not been extensively investigated to date. We studied olfactory function in vascular dementia (VD) and dementia of Alzheimer's type (DAT). Methods: We studied olfactory functioning in 12 patients suffering from dementia of Alzheimer's type, 11 patients with vascular dementia and 30 normal subjects. For these subjects we examined a 12‐item version of the Pennsylvania smell identification test and mini‐mental state examinations. These three groups were matched for age, sex and educational level. Results: Although the dementia scores were comparable in the DAT and VD groups, the smell identifications were low in DAT patients compared with VD patients and normal control subjects. Conclusions: These results suggest that the smell identification test may be useful in differential diagnosis between DAT and VD patients     

Differential verbal fluency deficits in the preclinical stages of Alzheimer's disease and vascular dementia

We examined patterns of early and late word generation in category and letter fluency among persons in the preclinical stages of Alzheimer's disease (AD) and vascular dementia (VaD). The sample consisted of 20 preclinical VaD persons, 66 preclinical AD persons, and 267 control persons, sampled from the community. Persons in the preclinical phase of AD and VaD were similarly impaired in letter fluency, although the preclinical VaD group outperformed their AD counterparts in category fluency. This pattern of results is consistent with the notion that category fluency is relatively more dependent on the medial-temporal lobe, whereas letter fluency relies more on frontal regions. The patterns of fluency impairment in preclinical AD and VaD generalized across early and late word retrieval.     

Prevalence of Alzheimer's disease, vascular dementia and dementia with Lewy bodies in a Japanese population

We studied the prevalence of dementing disorders in a rural town of Japan (Amino-cho), using a door-to-door two-phase design. Of the 170 persons screened as having cognitive impairment, 142 cases were diagnosed as having dementia. The prevalence (cases/100 aged 65 years older) was 3.8 for all types of dementia, 2.1 for Alzheimer's disease (AD), 1.0 for vascular dementia (VD) and 0.7 for other types of dementia. Among other types of dementia, there were four male patients with dementia with Lewy bodies (prevalence: 0.1), but no patients with frontotemporal lobar degeneration. The overall prevalence was higher in women for AD, while that of VD was the same in both sexes. With results similar to many previous studies in Western countries and some recent surveys in Japan, the present sudy clearly showed that AD is more prevalent than VD.     

阿尔茨海默氏病与血管性痴呆临床特点的对照研究

目的比较阿尔茨海默氏病（AD）与血管性痴呆（VD）的临床特点。方法对39例AD和38例VD患者的精神行为症状特点、伴随的躯体疾病、头颅CT检查以及脑电图检查进行比较。结果AD组与VD组在幻觉、妄想等精神病性症状方面无明显差异,在抑郁、焦虑等情绪障碍以及行为脱抑制方面有显著差异;AD组伴随的躯体疾病无明显特异性,VD组多伴发高血压、冠心病;AD组头颅CT多表现为脑萎缩,VD组多表现为脑梗塞;脑电图检查AD组无明显特异性,VD组界限脑电图居多。结论AD与VD患者的BPSD及所伴随的躯体疾病可有不同特点,CT和脑电图的检查等对痴呆的诊断与鉴别诊断均具有重要价值。     

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.     

阿尔茨海默病与血管性痴呆患者临床特征和影像学比较

目的 探讨阿尔茨海默病(AD)和血管性痴呆(VaD)患者的临床特征和影像学改变,以期寻找鉴别诊断的方法. 方法 收集武警广东医院老年病科自2006年8月至2011年6月收治的162例和同期本地区痴呆症状调查发现的42例痴呆患者的临床资料,采用简易精神状况检查(MMSE)量表进行筛选,其中AD患者114例、VaD患者90例,分析并比较AD、VaD患者的认知能力、行为症状和影像学资料. 结果 与VaD患者比较,AD患者女性较多,文化程度普遍较高,病程更长,差异有统计学意义(P＜0.05);VaD患者注意和计算分项评分低于AD患者,AD患者短程记忆、语言复述和阅读理解分项评分低于VaD患者,差异有统计学意义(P＜0.05); AD患者重复收敛行为的发生高于VaD患者,差异有统计学意义(P＜0.05);AD患者海马萎缩的比例高于VaD患者,VaD患者脑区域发生血管病变的发生率明显高于AD患者,差异均有统计学意义(P＜0.05). 结论 AD和VaD患者具有不同的临床特征和影像学改变,是由各自的病变本质、病变部位和病理机制所共同导致的.     

Apolipoprotein E polymorphism, Alzheimer's disease and vascular dementia among elderly Finnish men

An association between late-onset Alzheimer's disease, vascular dementia and the common polymorphic alleles of the gene coding for apolipoprotein E, ɛ2, ɛ3 and ɛ4, was assessed in a population sample of 393 elderly Finnish men aged 70 to 89 years. Of them, 7%, suffered Alzheimer's disease and 3% had vascular dementia. Among those who suffered Alzheimer's disease, there was a statistically significant excess of the ɛ4 allele. No such an association was observed between the apolipoprotein E alleles and vascular dementia. We conclude that the apolipoprotein E polymorphism confers information about a risk of Alzheimer's disease in this population sample of elderly Finnish men.     

Oligoclonal immunoglobulin bands in cerebrospinal fluid of patients with Alzheimer''s disease and vascular dementia

We examined serum and cerebrospinal fluid (CSF) of 16 patients with Alzheimer's disease (AD), 28 patients with vascular dementia (VD), their age-matched controls and multiple sclerosis (MS) patients in order to evaluate the humoral immune response within the central nervous system both quantitatively and qualitatively. Intra-blood-brain barrier (BBB) protein synthesis was calculated by CSF IgG index. The presence of oligoclonal banding (OCB) was investigated with agarose isoelectric focusing (IEF) followed by immunoblotting with antihuman IgG. No patient with AD and only 4 patients with VD had slightly elevated IgG indexes, and no statistically significant differences in the indexes were found between the two groups. No bands were found in the CSF of AD patients but 3 VD patients had OCB in both serum and CSF. One VD patient had bands in serum but no bands in CSF. No kappa or lambda free light chains were found in those demented patients with demonstrable bands in the CSF and serum. No OCB were found in control sera and CSF. For comparison, the majority of patients with MS had OCB in CSF. Thus, no consistent increase of intrathecal protein synthesis was found in patients with AD and VD. Methodological differences explain at least part of the conflicting results published earlier.     

Cognitive deficits of mild dementia:A comparison between dementia of the Alzheimer's type and vascular dementia

Abstract This study was designed to examine the profiles of cognitive deficits in 11 mildly demented patients with dementia of Alzheimer's type (DAT), five with vascular dementia with multiple subcortical lacunar infarcts (VDS), and seven with vascular dementia with extensive white matter lesions (VDW) in comparison with 23 aged individuals without dementia. Memory, attention, abstract thinking, and visuospatial function were assessed using the Japanese translation of the Wechsler Memory Scale-Revised (WMS-R) and the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Compared with normal aged individuals, three dementia groups were significantly impaired in the memory and abstract thinking. However, the performances on several tests on attention (i.e. Mental Control and Visual Memory Span Backward from WMS-R) and visuospatial function (i.e. Object Assembly from WAIS-R) differed significantly between the DAT and VDS groups, with VDS being the worst in terms of performance than was DAT. This study suggests that, in the mildly demented stage, the patients with DAT have few problems in the attention and visuospatial function, but those with VDS have impairments in these cognitive abilities.     

Serum and cerebrospinal fluid cystatin C levels in vascular and Alzheimer's dementia

INTRODUCTION: Cystatin C, a cysteine protease inhibitor, has been implicated in the neurodegenerative and repair processes of the nervous system, and the deposition of the same protein together with beta amyloid peptide was found as cerebral amyloid angiopathy (CAA) in different types of dementias. OBJECTIVE AND METHODS: Because of the differential diagnostic importance, serum and cerebrospinal fluid (CSF) cystatin C levels of 24 late onset Alzheimer's demented (AD) and 16 ischemic type of vascular demented (VD) probands were compared with 17 aged control (AC) persons. RESULTS: The serum and CSF cystatin levels were found in the normal range in all groups. The ischemic VD probands had the tendency to have higher cystatin C levels than the AD. No correlation has been found with the severity and duration of dementia and with the other measured parameters. CONCLUSION: These results indicate that lower than normal CSF cystatin C level is not a diagnostic marker in ischemic VD and CAA related to AD.     

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.     

老年性阿尔茨海默病与血管性痴呆患者的行为和精神症状的比较

目的探讨阿尔茨海默病痴呆患者的行为和精神症状。方法选取本院2011年5月至2015年5月诊治的痴呆性老年患者80例,其中血管性痴呆(VD)患者40例为VD组,阿尔茨海默病(AD)患者40例为AD组,均行AD行为评分表(Behave-AD)评定,比较两组患者的行为和精神症状。结果 AD组患者偏执和妄想发生率、行为紊乱发生率、攻击行为发生率、焦虑和恐惧发生率均明显高于VD组,AD组患者偏执和妄想评分、行为紊乱评分、攻击行为评分、焦虑和恐惧评分、总评分均明显高于VD组,差异有统计学意义(P0.05)。AD组患者幻觉发生率高于VD组,AD组患者日间节律紊乱发生率、情感障碍发生率均低于VD组,AD组患者幻觉评分高于VD组,AD组患者日间节律紊乱评分、情感障碍评分均低于VD组,但差异无统计学意义(P0.05)。结论 AD患者偏执和妄想、行为紊乱、攻击行为、焦虑和恐惧等病症较为严重,其发生机制可能与AD患者存在较明显的额-枕叶萎缩有关。     

Neuropsychological differentiation between normal aging, Alzheimer''s disease and vascular dementia

A random sample of 182 elderly community residents and 211 demented patients were studied using the D-Test Battery based on the Luria's neuropsychological investigation method. A steady but selective cognitive impairment was observed with increasing age in normal healthy subjects. The most sensitive areas of cognition to the effects of normal aging were mnestic and conceptual functions, as well as arithmetical skills. The age-related changes could be clearly differentiated from the changes found in patients with mild degree of dementia. The test also differentiated patients with mild, moderate and severe dementia from each other on the basis of their social competence. It failed to demonstrate specific patterns of impairment and to clearly differentiate between patients with Alzheimer's disease and vascular dementia who had the same degree of cognitive decline. Further qualitative analyses are needed to improve the sensitivity and specificity of the test.     

Alzheimer's disease and frontal variant of frontotemporal dementia

The aim of this study was to investigate whether a brief neuropsychological battery consisting of a limited number of cognitive tests and an evaluation of the behavioural domains intended to discriminate between frontotemporal dementia (fv–FTD) and Alzheimer's disease (AD), constitutes a useful instrument for making a differential clinical diagnosis between these two pathologies. Nineteen fv–FTD and 39 AD patients were compared on cognitive tasks (assessing memory, executive functions, language and constructional praxis) and on the NPI behavioural assessment. A stepwise discriminant analysis was performed to identify the linear combination of cognitive and behavioural measures able to best discriminate between the two groups. One test for each of the investigated cognitive domains (Delayed Prose Recall, FAS verbal fluency, Boston naming test, Rey's Figure A Copy) and the four subscales of the Neuropsychiatry Inventory (NPI) which best differentiated between fv–FTD and AD patients (apathy, disinhibition, euphoria, aberrant motor behaviour) were used. The analysis selected Rey's Figure A Copy, FAS verbal fluency and NPI apathy subscale as the best discriminants between fv–FTD and AD patients. The final equation assigned 73.7% of the fv–FTD patients and 94.7% of the AD patients to the correct diagnostic group. A validation study conducted on a new independent sample of 11 fv–FTD and 22 AD patients confirmed the high sensitivity (82.6 %) and specificity (81.8%) of the diagnostic equation in assigning fv–FTD and AD patients to the correct dementia group. Although both cognitive and behavioural differences exist between FTD and AD, previous studies have aimed at differentiating the two pathologies by considering the two aspects separately and discriminant analyses were focused only on neuropsychological or neuropsychiatric evaluations. The present results emphasise the importance of rating both cognitive and behavioural clinical features of the two syndromes as objectively as possible to improve differential diagnostic accuracy.     

Apolipoprotein E phenotypes in healthy normal controls and demented subjects with Alzheimer's disease and vascular dementia in Mie Prefecture of Japan

In order to clarify the association between apolipoprotein E4 (ApoE4) and the pathogenesis of Alzheimer's disease (AD), we analyzed the distribution of the apolipoprotein E (ApoE) phenotypes and the frequency of the apo E alleles epsilon2, epsilon3, and epsilon4 in Japanese healthy controls (n = 1090, an average age of 51.2+/-12.6 years) and demented patients (n=103, mean age of 73.6+/-9.2 years). Demented subjects were divided into three subgroups: early-onset AD group (EOAD; n=25, mean age 63.0+/-6.2 years), late-onset AD group (LOAD; n=33, mean age 79.3+/-5.1 years), and vascular dementia group (VD; n=45, mean age 75.3+/-8.0 years). The apolipoprotein E phenotype was determined by isoelectric focusing and immunoblotting. There were no significant differences in the distribution of the apo E phenotypes by gender or age, and the estimated frequencies of epsilon2, epsilon3 and epsilon4 were 0.05, 0.86 and 0.09, respectively, in the normal controls. There was a significant difference in the distribution of the apo E phenotypes between LOAD and elderly controls aged more than 65 years (P<0.0001). The distribution of the apo E phenotypes in EOAD was the same as that in LOAD. The frequency of the epsilon4 allele was significantly higher in LOAD (0.35, P<0.0001) and EOAD (0.28, P<0.0001) than that in the control subjects (0.07), but not in VD (0.12, P=0.1630). The present findings suggest that ApoE4 is related with both EOAD and LOAD, but not with VD, and support the hypothesis that it is a genetic risk factor of AD.