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.     

Olfactory identification is impaired in clinic-based patients with vascular dementia and senile dementia of Alzheimer type

AIMS: It is now well established that there are abnormalities in the sense of smell in patients suffering from Alzheimer's disease (AD). They have both raised olfactory thresholds and impaired odour identification. The situation in vascular dementia is unclear. We used the University of Pennsylvania Smell Identification Test (UPSIT), a 40-item, forced choice, cued, 'scratch-and- sniff' test, to examine olfactory identification in vascular dementia and to determine whether it would differentiate the disorder from AD and normal elderly. METHODS: We investigated three matched subject groups: 13 people having a Cambridge Examination for Mental Disorders in the Elderly (CAMDEX) diagnosis of definite senile dementia of Alzheimer type, 13 having a CAMDEX diagnosis of definite vascular dementia and 13 non-cognitively impaired controls. The subjects were then tested with the UPSIT in their own home by an independent blind researcher to see if the test could distinguish the different diagnostic groups in this setting. RESULTS: The median UPSIT score was 30 (out of a maximum of 40) for controls, 12 for the vascular group and 15 for the AD group. The difference was significant (p = 0.05) between both demented groups and the normal controls. Similarly there was a significant difference in the UPSIT score between the AD group and controls (p = 0.001) and between the vascular dementia group and controls (p = 0.001), but there was no significant difference between the AD group and the vascular dementia group. The UPSIT score correlated strongly with the degree of cognitive impairment as measured by the CAMCOG (r(s) = 0.683, p = 0.01) CONCLUSIONS: Patients with vascular dementia had a similar degree of olfactory impairment to those with AD. The UPSIT successfully differentiated between dementia patients and normal elderly British subjects tested in their own homes. The UPSIT did not differentiate between those with AD and vascular dementia.     

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     

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.     

Apolipoprotein E in patients with dementia of the Alzheimer type and vascular dementia

The phenotypes of apolioprotein E (ApoE) in the plasma of patients with dementia of the Alzheimer type (DAT) and vascular dementia (VD) were determined by the isoelectric focusing method. The ApoE mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the control subjects, the frequency of the ApoE ε4 allele was significantly higher in the DAT group as well as the VD group, but was not significantly different in the cerebrovascular disease without dementia (CVD) group. The skin fibroblast ApoE mRNA level in the DAT group and the VD group was significantly lower than that in the control group. These findings suggest that the phenotype of ApoE is associated with DAT and VD, and that the lower level of ApoE mRNA may play an important role in the development of DAT as well as VD.     

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.     

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.     

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.     

99mTc-HMPAO-SPECT in the diagnosis of senile dementia of Alzheimer's type — a study under clinical routine conditions

Summary This study was designed to evaluate, whether investigations of cerebral blood flow can be a helpful diagnostic tool in the differential diagnosis between (senile) dementia of Alzheimer's type [(S)DAT] and geriatric depression with cognitive impairment. Under clinical routine conditions we performed Single Photon Emission Computed Tomography (SPECT) using^99mTc-Hexa-methylpropyleneamine Oxime (HMPAO) in 23 patients with (S)DAT (14 f, 9 m; mean age 68.9 y), 17 patients with geriatric depression (9 f, 8 m; mean age 66.4 y) and 12 age-matched controls (9 f, 3m; mean age 69.2 y). Semiquantitative analysis (corticocerebellar ratios) of eight different regions of interest (ROI) revealed a significantly (p < 0.05) reduced perfusion in the (S)DAT patients compared to the control group. The depression group exhibited perfusion values between the (S)DAT and control group. The difference between the depression and (S)DAT group was most prominent in the left parieto-occipital ROI (p=0.008). We discuss the data with extensive regard to the literature and conclude that^99mTc-HMPAO SPECT is a valuable additional tool in the differential diagnosis of depression and dementia in the elderly.     

Concentration of monoamines and their metabolites in the cerebrospinal fluid from patients with senile dementia of the Alzheimer type and vascular dementia of the Binswanger type

Summary We measured the concentrations of total (conjugated and unconjugated) monoamines (dopamine, DA; norepinephrine, NE) and monoamine metabolites (homovanillic acid, HVA; 3-methoxy-4-hydroxyphenyleneglycol, MHPG; 5-hydroxyindoleacetic acid, 5-HIAA) in the cerebrospinal fluid (CSF), using HPLC-ECD in 11 patients with Alzheimer's disease (AD) or senile dementia of the Alzheimer type (SDAT), 17 patients with vascular dementia of the Binswanger type (VDBT), and 15 controls. In AD/SDAT, there was a significant decrease in the DA concentration and a significant increase in the MHPG concentration. The average NE concentration was not altered, but significantly increased with the progression of intellectual disability. There were no significant changes in HVA and 5-HIAA concentrations. Patients with VDBT showed a significant increase in the DA concentration and a significant decrease in HVA and 5-HIAA concentrations. The DA concentrations increased significantly with the progression of dementia and ventricular enlargement. These results indicate that the noradrenergic and dopaminergic system in particular are altered in AD/SDAT, while the dopaminergic and serotonergic systems are mainly involved in VDBT.     

Increased chemiluminescence response of neutrophils from the peripheral blood of patients with senile dementia of the Alzheimer's type

The metabolic activity of circulating neutrophils from patients with senile dementia of the Alzheimer's type (SDAT) was investigated by a chemiluminescence assay and compared with that of old and young healthy controls. Neutrophils from demented patients showed a higher and faster chemiluminescence emission than those of controls when activated in vitro by autologous or heterologous sera. Granulocytes from patients with Parkinson's disease did not show an increased chemiluminescence activity. Moreover, serum from patients with SDAT depressed the chemiluminescence emission of granulocytes from young donors. Serum levels of α₁-antichymotrypsin (α₁-ACT) were also determined and were found to be higher in demented subjects than in old and young controls. These data suggest that peripheral and systemic indexes of inflammation are present in the disease and might be associated with mental deterioration.     

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。     

The urate and xanthine concentrations in the cerebrospinal fluid in patients with vascular dementia of the Binswanger type, Alzheimer type dementia, and Parkinson's disease

Summary We determined the urate and xanthine concentrations in the cerebrospinal fluid (CSF) in patients with vascular dementia of the Binswanger type (VDBT), Alzheimer type dementia (ATD), and Parkinson's disease (PD). We found that the urate concentration was significantly increased in VDBT patients, but significantly decreased in ATD patients compared with controls. The ratio of the concentrations of uric acid (U_CSF) to xanthine (X_CSF) in the CSF (U_CSF/X_CSF) had a significant correlation with the ratio of the U_CSF to the urate concentration in serum (U_serum) (U_CSF/U_serum) in ATD and PD, whereas U_CSF/U_serum increased independently of U_CSF/X_CSF in VDBT. We concluded that the significant increase in the urate concentration in VDBT is mainly due to an impairment of the blood-brain barrier (BBB), and its significant reduction in ATD may reflect impaired brain metabolism.     

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.     

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.     

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.     

Parkinson's disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson's, Alzheimer's and vascular dementia patients

Summary. Antioxidant profiles in Parkinson's disease (PD; n = 15), dementias of Alzheimer's type (DAT; 18) and Vascular (VD; 15), and control subjects (C; 14) were studied. Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione system (GLU) and thiobarbituric acid reactive substances (TBARS) were measured in erythrocytes; antioxidant capacity (TRAP) in plasma. Biochemical variables were analyzed simultaneously using multivariate and non-parametric methods. Clinical diagnostic resulted associated with the main source of variability in antioxidant variables (Kruskal-Wallis: H = 32.58, p = 0.000001). Comparison of PD and C resulted highly significant (z = 4.47, p = 0.000047), demonstrating an association between oxidative stress and PD. SOD and TBARS were significantly higher in pathological groups against C (p = 0.0000001, p = 0.051); TRAP resulted lower (p = 0.00015). Discriminant functions constructed using biochemical variables separated pathological groups (93% success) from C, and DAT (88.9%) from VD (73.3%); but not PD from DAT or VD. Antioxidant profiles of PD patients showed characteristics overlapping with DAT (60%) and with VD (40%), suggesting biochemical similarities between them. Received October 5, 2000; accepted June 1, 2001     

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.     

Visual cognitive function in dementia of Alzheimer's type: a comparison of visual event-related potentials and Stroop test

Background: Many published studies on dementia of Alzheimer’s type (DAT) have utilized event‐related potentials (ERP) and the Stroop test. However, most of this research has performed these analyses separately. Therefore, in the present research, these two examinations were carried out together following the same paradigm in order to clarify the characteristics of visual dysfunction in DAT patients. Methods: Subjects included 30 normal adults, 10 normal elderly and 10 DAT patients. A visual categorically deviant paradigm was utilized during ERP measurement. The target stimulus was red and non‐target stimuli were blue, yellow and green. The stimuli were displayed as square figures. During the Stroop test, the subjects read color names from word cards, named colors from color cards, and the text color of a printed color word. Reading times and differences in reading times were measured for each task. Results: Regarding ERP, the normal elderly and DAT groups displayed increased latencies and decreased amplitudes compared to the normal adult group. The normal elderly and DAT groups displayed no significant differences in N100 latencies and amplitudes. However, for P300, the DAT group displayed significantly decreased amplitudes in comparison to the normal elderly group. On the Stroop test, the normal elderly and DAT groups displayed significantly extended differences in reading times compared to the normal adult group. No significant differences were observed between the normal elderly and DAT groups. Conclusion: Age‐related changes were observed in the latency of ERP and the increase of the Stroop effect. Characteristic changes in DAT were indicated by latencies and amplitudes of P300, but were not indicated by the Stroop test. Characteristic abnormalities in the stimulation evaluation process were observed for DAT; however, changes other than those related to aging were not apparent in the selection process reaction.