Olfactory dysfunction discriminates probable Alzheimer's dementia from major depression: a cross-validation and extension

The present study was conducted to cross-validate and extend the hypothesis that olfactory dysfunction could discriminate between groups of patients with Alzheimer's disease and major depression. Forty patients meeting the DSM-IV criteria for either Alzheimer's disease or major depression (20 per group) underwent assessment with the Pocket Smell Test (PST), a three-item screening measure of odor identification, and the Mini-Mental State Examination (MMSE). A PST score of < or = 1 (1 or 0 correct) discriminated between the groups with a hit rate of 97.5% (sensitivity = 95%, specificity = 100%). The optimal hit rate for the MMSE (< or =24) was less effective (hit rate = 90%, sensitivity = 80%, specificity = 100%). Age, gender, and education had minimal impact on the PST for both groups. Olfactory assessment continues to add to the diagnostic utility in the differential diagnosis of Alzheimer's disease versus major depression in elderly patients.     

Validity of the Short-Memory Questionnaire in vascular dementia

PURPOSE. To determine whether the Short-Memory Questionnaire (SMQ) being administered by caregivers to patients with Alzheimer's disease (AD) is also valid when given to patients with vascular dementia (VaD). METHODS. Subjects were 58 patients with VaD, 26 patients with cerebrovascular disorders free of cognitive deficit (CVD) and 62 healthy controls. All subjects received the Mini-Mental State Examination (MMSE), and their primary caregivers (or family members with same household) received the SMQ. RESULTS. In the VaD patients, the SMQ score was highly correlated with the MMSE score. When 39/40 was defined as a cutoff point based on the results of previous study, the SMQ properly classified 55 of the 58 VaD patients and 61 of the 62 controls, but only about half of the 26 CVD patients, as cases. CONCLUSION. The SMQ, a simple quantitative rating test for memory disturbance, is useful for the assessment and screening of VaD patients as well as AD patients, although careful attention should be paid to the assessment of CVD patients.     

不同严重程度血管性痴呆与老年性痴呆的神经心理特点

目的 探讨不同严重程度的血管性痴呆（vascular dementia,VaD）与老年性痴呆（Alzheimer disease,AD）
的神经心理学特点。
方法 对广东省人民医院神经科门诊及病房的252例痴呆患者（VaD组127例,AD组125例）,和正常对
照组159例进行一组神经心理量表检查。神经心理量表包括：简易精神状态检查（mini-mental state
examination,MMSE）、Fuld物体记忆测验（fuld object memory,FOM）、言语流畅性测验（rapid verbal
retrieve,RVR）、数字广度测验（digit span,DS）和积木测验（block design,BD）。分析这两种类型不同
严重程度的痴呆患者认知障碍的特点。
结果 两种类型的轻、中、重度痴呆患者神经心理检查有统计学差异（P <0.01）。轻度痴呆患者MMSE、
RVR评分在VaD、AD组间存在统计学差异（P <0.05）,在中、重度痴呆患者,神经心理评分在VaD、AD组
间无统计学差异（P >0.05）。
结论 神经心理量表评估有助于VaD、AD的严重程度分级,RVR测验可辅助鉴别诊断轻度VaD和AD。     

Validation of the Addenbrooke's cognitive examination for detecting early Alzheimer's disease and mild vascular dementia in a German population

We assessed the diagnostic accuracy of the German version of the Addenbrooke's Cognitive Examination (ACE) in identifying early Alzheimer's disease (AD) and mild vascular dementia (VaD) in comparison with the conventional Mini-Mental State Examination (MMSE). The study refers to 50 patients with mild dementia of AD, 26 patients with mild dementia of vascular etiology and to 54 cognitively normal subjects. The ACE and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic workup. Statistical analysis was performed using the receiver operator characteristics method. The optimal cut-off score for the ACE for detecting dementia in patients with early AD was 85/86, which had a sensitivity of 93% and a specificity of 86%. The optimal cut-off for the ACE for the identification of dementia in patients with mild VaD was also 85/86 and it had a sensitivity of 93% and a specificity of 100%. The kappa values imply a substantial agreement between the diagnoses made by the ACE and the MMSE. The German version of the ACE is a short and practical but accurate test battery for the identification of AD and VaD, assessing a broad range of cognitive functions and providing a wide profile of cognitive functions/dysfunctions.     

同型半胱氨酸与阿尔茨海默病及血管性痴呆

目的研究同型半胱氨酸(Homocysteine,Hcy)及叶酸、维生素B_(12)与阿尔茨海默病(Alzheimer Dis- ease,AD)和血管性痴呆(Vascular dementia,VaD)的关系,并通过Hcy揭示AD发病的血管危险因素。方法用美国国立神经病学、语言障碍和卒中-阿尔茨海默病和相关疾病学会(NINCDS-ADRDA)标准的可能标准严格筛选AD患者35例,用ADDTC诊断标准筛选VaD患者30例,并同期选择31例无临床脑血管病史、无认知功能障碍的健康查体中心志愿者为对照组。取肝素抗凝的血浆用循环酶法进行Hcy的测定。取血清由全自动化学发光免疫检测仪进行叶酸和维生素B_(12)的测定。结果AD组和VaD组血浆Hcy水平显著高于对照组,血清叶酸和VitB_(12)水平显著低于对照组。VaD组存在痴呆程度越高血浆Hcy水平越高这一显著正相关关系,而AD组这一正相关关系无统计学意义;且发现VaD组患者MMSE评分越低其血浆Hcy水平越高这一显著负相关关系,而AD组这一关系仍无统计学意义。在所有研究对象中存在血浆Hcy水平与血清叶酸及VitB_(12)水平的显著负相关关系。结论提示高Hcy血症可能是引起AD和VaD的一个重要危险因素,Hcy作为一个新的血管因素加强了AD与血管危险因素之间的联系,并且提示积极治疗高Hcy血症在预防AD和VaD方面可能有积极意义。     

Neuropathological evaluation of mixed dementia

Mixed dementia (MD) refers to a combination of definite Alzheimer disease (AD) and vascular encephalopathy, but the distinction between both disorders is controversial. For the diagnosis of MD the clinical/neuroimaging criteria of possible AD plus cerebrovascular disease (CVD) as separate entities are used, but causal relations between vascular brain lesions and dementia are unclear. We proposed the combination of autopsy-proven AD with multiple vascular or ischemic lesions with about 30-50 ml of infarcted/damaged brain tissue. The population-based prevalence of MD is unknown. In retrospective and prospective autopsy studies, it ranges from 2 to 58% with reasonable means of 6-12%. In a consecutive autopsy series of 1500 demented elderly subjects, 830 of which with clinically probable AD, in Vienna, Austria, 41.5 to 52.0% showed "pure" AD, 7% atypical AD, 16-20% AD plus cerebrovascular lesions, and 9% AD plus Lewy body pathology; MD was diagnosed in 4.6 and 2.4%, and "pure" vascular dementia (VaD) in 11 and 2.0%, respectively, while 16.3/6.1% were other dementing disorders, and 1% showed no specific pathology. Like the MRC-CFAS and other studies, this indicates frequent coexistence of AD with multiple cerebrovascular lesions in cognitively impaired patients. In both AD and VaD, vascular lesions frequently involved subcortical regions (basal ganglia, thalamus, hippocampus, and white matter) or were multiple microinfarcts, whereas in MD, large/hemispheral infarcts and multiple microinfarcts were more frequent, suggesting different pathogenic mechanisms. In early/mild AD, critically located small vascular lesions may induce/promote cognitive decline, but in full-blown AD they appear of minor importance. Discussion of the major pathogenic factors inducing AD, VaD and MD suggests synergistic relations between these disorders. However, currently available morphological criteria for AD and VaD are of limited value for the diagnosis of MD and generally accepted and validated histopathological criteria for the diagnosis of VaD and MD are currently not available. Therefore, more distinct and critically evaluated clinico-pathological criteria are warranted.     

The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer's disease

BACKGROUND: Little is known about the rate of progression or associations of cognitive impairment in dementia with Lewy bodies (DLB), or the associations of accelerated decline. METHOD: Dementia patients from a case register were evaluated at baseline and 1 year follow-up using the Cambridge Assessment for Mental Disorders in the Elderly, section B (CAMCOG) and the Mini-Mental State Examination (MMSE) to determine the rate of cognitive decline. Operationalized clinical diagnoses were applied (NINCDS ADRDA for Alzheimer's disease (AD), NINCDS AIRENS for vascular dementia (VaD) and consensus criteria for DLB). RESULTS: One hundred and ninety-three patients completed annual MMSE schedules (AD, 101; DLB, 64; VaD, 38), of whom 154 completed the CAMCOG. The magnitude of cognitive decline (MMSE, 4-5 points; CAMCOG, 12-14 points) was similar in each of the dementias. The strongest predictor of accelerated cognitive decline in DLB was the apolipoprotein E4 allele (17.5 vs 8.3 points decline on the CAMCOG). CONCLUSION: Over 1 year, DLB, VaD and AD patients had similar rates of cognitive decline overall. Apolipoprotein E4 may be an important predictor of more rapid decline in DLB.     

One year follow-up of parkinsonism in dementia with Lewy bodies

The progression of parkinsonism over 1 year was evaluated in a prospective cohort of patients (n = 338), suffering from dementia with Lewy bodies (DLB), Alzheimer's disease (AD) or vascular dementia (VaD). Parkinsonism was assessed using the modified Unified Parkinson's Disease Rating Scale. Significant parkinsonism was significantly commoner in DLB sufferers (71%) than amongst patients with AD (7%) or VaD (10%). DLB patients with established parkinsonism had an annual increase in severity of 9%, but progression was more rapid (49% in 1 year) in patients with early parkinsonism. Parkinsonism was frequent at all severities in DLB patients, but usually only present in other dementias when MMSE <10.     

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.     

18FDG PET in vascular dementia: differentiation from Alzheimer's disease using voxel-based multivariate analysis.

The brain metabolic pattern of vascular dementia (VaD) remains poorly characterized. Univariate voxel-based analysis ignores the functional correlations among structures and may lack sensitivity and specificity. Here, we applied a novel voxel-based multivariate technique to a large ((18)F)2-fluoro-2-deoxy-D-glucose positron emission tomography data set. The sample consisted of 153 subjects, one-third each being probable subcortical VaD, probable Alzheimer disease (AD) (matched for Mini-Mental-State examination (MMSE) and age), and normal controls (NCs). We first applied principal component (PC) analysis and removed PCs significantly correlated to age. The remainders were used as feature vectors in a canonical variate analysis to generate canonical variates (CVs), that is, linear combinations of PC-scores. The first two CVs efficiently separated the groups. CV(1) separated VaD from AD with 100% accuracy, whereas CV(2) separated NC from demented subjects with 72% sensitivity and 96% specificity. Images depicting CV(1) and CV(2) showed that lower metabolism differentiating VaD from AD mainly concerned the deep gray nuclei, cerebellum, primary cortices, middle temporal gyrus, and anterior cingulate gyrus, whereas lower metabolism in AD versus VaD concerned mainly the hippocampal region and orbitofrontal, posterior cingulate, and posterior parietal cortices. The hypometabolic pattern common to VaD and AD mainly concerned the posterior parietal, precuneus, posterior cingulate, prefrontal, and anterior hippocampal regions, and linearly correlated with the MMSE. This study shows the potential of voxel-based multivariate methods to highlight independent functional networks in dementing diseases. By maximizing the separation between groups, this method extracted a metabolic pattern that efficiently differentiated VaD and AD.     

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.     

Differences in risk factors for dementia with neurodegenerative traits and for vascular dementia

In 229 patients with dementia and in 144 control subjects, polymorphisms of apolipoprotein E (ApoE), low-density-lipoprotein (LDL)-receptor-related protein, alpha(2)-macroglobulin, interleukin (IL) 1beta, angiotensin-converting enzyme and of methylene tetrahydrofolate reductase genes were investigated. In plasma, antibodies against Chlamydia pneumoniae and lipids were determined. Dementia was classified as probable Alzheimer's disease (AD), probable dementia of vascular origin (VaD) and mixed dementia (MD). An association of the disease with ApoE and IL-1beta polymorphism and increased levels of LDL cholesterol were observed in AD and in MD but not in VaD.     

Apolipoprotein E genotypes in hospitalized elderly patients with vascular dementia

BACKGROUND: Polymorphism in the apolipoprotein E (APOE) gene is the major genetic risk factor associated with late-onset Alzheimer's Disease (AD). However, it is still unclear if a relationship exists between the APOE epsilon4 allele and vascular dementia (VaD) in elderly subjects. OBJECTIVES: To evaluate the prevalence of APOE alleles in elderly patients with VaD compared to AD patients and to control subjects with no cognitive impairment (NoCI). PATIENTS AND METHODS: We evaluated 396 consecutive patients aged > or =65 years with definite or suspected cognitive impairment with a clinical (Mini-Mental State Examination, Clinical Dementia Rating, Geriatric Depression Scale), functional (Activities of Daily Living, Instrumental Activities of Daily Living), comorbidity (Cumulative Illness Rating Scale) and instrumental (CT scan, NMR) assessment. Diagnosis of dementia was made according to NINCDS-ADRDA and NINDS-AIREN Work Group and the DSM-IV. APOE genotypes were analyzed by a recently described method resulting in positive/negative chain reaction products for each APOE genotype. Statistical analysis was carried out using the Pearson chi(2), the Kruskal-Wallis test and the ANOVA post hoc comparisons. RESULTS: A total of 287 elderly patients (males = 138, females = 149, mean age = 77.8 +/- 6.9 years, range = 65-98) with diagnoses of VaD (n = 97), AD (n = 82) or NoCI (n = 108) were included in the study. A significantly higher APOE epsilon4 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects, while no differences were found between VaD patients and subjects with NoCI (AD = 24.3%, VaD = 10.3, NoCI = 8.7, p < 0.05). Furthermore, a significantly lower APOE epsilon3 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects but not between VaD and NoCI patients (AD = 71.3%, VaD = 80.9, NoCI = 83.4, p < 0.05). No significant differences were observed in the APOE epsilon2 allele (VaD = 8.8%, AD = 4.4, NoCI = 7.9, p = n.s.) among the 3 groups. CONCLUSIONS: In this population, the frequency of the APOE epsilon4 allele is lower in VaD than in AD.     

血管性痴呆患者电生理应用研究

目的观察血管性痴呆（vasculardementia,VaD）患者事件相关电位P300与脑电图（elec-troencephalography,EEG）的改变并探讨其临床意义。方法将124例脑卒中患者根据是否伴有痴呆分为VaD组和非VaD组,所有患者同时进行P300和EEG检查,用简易智能量表（Mini-MentalStateEx-amination,MMSE）考核其智能,比较P300潜伏期的延长率和EEG异常率在VaD组和非VaD组患者间的差异,分析患者P300潜伏期与MMSE得分的相关性,以及EEG改变与VaD患者痴呆程度的关系。结果VaD组和非VaD组患者P300潜伏期延长率分别为74.2%和6.7%,两组患者间差异有显著性（P〈0.01）,患者P300潜伏期与MMSE得分呈负相关。VaD患者EEG异常率达75%,而且患者EEG改变愈明显,其痴呆愈严重。结论P300潜伏期与EEG均可以作为VaD患者诊断和考核疗效的客观指标;对VaD患者同时进行P300和EEG检查可明显提高VaD患者的检出率。     

Mirror writing in elderly patients with Alzheimer disease and vascular dementia

BACKGROUND: The results showed that mirror writing (MW) was correlated with the development of written language, so that MW examination may be one of methods to examine the intelligence of elderly people. OBJECTIVE: To study the MW in elderly patients with Alzheimer disease (AD) and vascular dementia (VaD) and take appropriate scale for their evaluation. DESIGN: Taking the written portion of the Chinese Aphasia Examination Scale (1994) for assessment. SETTING: Department of Neurology, Neuropsychological Laboratory, Beijing Hospital. PARTICIPANTS: From March 1998 to January 2001, 33 patients with AD, 30 patients with VaD admitted into Department of Neurology, Beijing Hospital was enrolled into study. Criteria according to the Diagnostic and Statistical Manual of Mental Disorder, 4th edition (DSM-IV), published by the American Psychiatric Association was used to diagnose AD, while criteria according to the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l’ Enseignement en Neurosciences (NINDS-AIREN) and Alzheimer Disease Diagnostic and Treatment Center (ADDCT) were used for diagnosis of VaD. AD group contained 19 males and 14 females aged 60–83 years. Twenty-eight males and 2 females, aged 60–87 years made up the VaD group. The 63 healthy elderly subjects matched on age and education as controls were enrolled into study. The matched controls were categorized AD control (n =33) and VaD control (n =30). All patients and controls were understanding and agree with all items of assessment. METHODS: MW examination, Mini Mental State Examination (MMSE), Hachinski Ischemic Scale, the Global Deterioration Scale (GDS) were examined in all subjects. ① Use the written potion of the Chinese Aphasia examination Scale (1994), patient using MW for 91%–100% of dictation had complete MW, those using MW for 51%–90% of dictation had severe MW, those using MW for 11%–50% had moderate MW, those using MW for 1%–10% had mild MW. ② According to the MMSE, the patients were considered to have dementia if they were illiterate and had an MMSE score ≤ 17 score or educated time ≤ 6 years and MMSE ≤ 20 score or educated time > 6 years and MMSE ≤ 24 score. ③ Using the Hachinski Ischemic Scale to differentiate the AD and VaD, it included 6 items and total 9 scores. > 7 score was VaD, < 4 score was AD and 4–7 score was blended dementia. ④ Using the GDS to assess cognitive function: Standard criteria were divided in 7 degrees: 1 degree: no impairment of cognition and 7 degree: very severe impairment of cognition. MAIN OUTCOME MEASURES: The data of MW examination, evaluation of MMSE, Hachinski Ischemic Scale and the GDS of all assessed subjects. RESULTS: All 63 cases of AD and VaD and 63 healthy controls were entered for analysis. ①Results of MW examination: A total of 17 patients with AD were characterized as using MW, 3 with moderate MW and 14 patients with mild MW. In the corresponding control group, only 2 subjects were characterized as being mild MW. The VaD group has 23 patients with MW, 2 with moderate and 21 patients with mild MW. ② MMSE score: MMSE score of AD group was much lower than that of individuals in control group [(20.15±3.40), (29.73±0.40) score, P < 0.01], MMSE score of VaD group was much lower than that of individuals in control group [(19.33±2.75), (29.12±0.63) score, P < 0.01]. ③ Hachinski Ischemic Scale and GDS score: Rating according to the Hachinski Ischemic Scale was higher in VaD patients compared to AD patients [(9.61±1.69), (1.09±0.60) score, P < 0.01]. The GDS score did not significantly differ between the AD group and the VaD group. CONCLUSION: ① MW examination could be used as an indicator of intelligence in healthy elderly people and also could be used as one of methods to assess the intelligence in AD and VaD patients. ② Grade of severity of MW may indirectly reflect the degree of dementia.     

血清晚期糖基化终末产物和可溶性晚期糖基化终末产物受体与阿尔茨海默病及血管性痴呆关系的研究

目的探讨血清中晚期糖基化终末产物(AGEs)、可溶性晚期糖基化终末产物受体(sRAGE)的水平与阿尔茨海默病(AD)、血管性痴呆(Va D)的关系。方法收集兰州大学第二医院神经内科2017年2月到2018年1月收治的149例患者,根据MMSE量表及相应的纳入排除标准,将患者进行分组,其中AD组34例,脑梗死后痴呆(Va D)组64例,脑梗死非痴呆(N-Va D)组51例,选择同期在性别、年龄、文化程度上无差异、无严重疾病的住院体检者31例作为正常对照组。比较4组间的一般资料及简易智能精神状态检查量表(MMSE)评分,比较血清AGEs、sRAGE在不同组别之间的差异,并分析其与AD和Va D的关系。结果 AD组和N-Va D组的AGEs水平高于Va D组和正常对照组,差异有统计学意义(P 0. 05)。Va D组和正常对照组之间,AD组和N-Va D组之间的AGEs水平比较,差异无统计学意义(P 0. 05)。ROC曲线分析显示血清AGEs对AD有较低诊断价值。Spearman秩相关法分析显示,年龄(r=-0. 168,P 0. 05)与MMSE评分呈负相关;体重指数(r=0. 151,P 0. 05)与MMSE评分呈正相关。4组在性别、年龄、糖尿病方面不存在显著性差异(P 0. 05)。4组间sRAGE水平比较无显著性差异(P 0. 05)。结论血清AGEs可能与AD的发生、发展有关; AGEs对AD有较低的诊断价值。     

Vascular dementia in a population-based autopsy study

BACKGROUND: The validity of the clinical diagnosis of vascular dementia (VaD) remains suboptimal. OBJECTIVE: To investigate clinicopathologic correlations in VaD. METHODS: We used the medical records-linkage system of the Rochester Epidemiology Project to identify incident cases of dementia in Rochester, Minn, from January 1, 1985, through December 31, 1989. Dementia and Alzheimer disease (AD) were defined by the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Vascular dementia was defined by criteria including imaging results. Pathological characteristics of AD were quantified by means of standard scoring methods for neurofibrillary tangles and neuritic plaques. Vascular pathological findings were assessed by expert neuropathological opinion. RESULTS: Of 419 patients with dementia who died before the study, neuropathological examination results were available in 89 (21%) with median age at onset of 80 years (range, 50-96 years; 52 [58%] women). Pathological diagnoses were AD in 45 patients (51%), pure VaD in 12 (13%), combined AD and VaD in 11 (12%), and other diagnoses in the remaining 21 patients. Criteria for VaD that required either a temporal relationship between a stroke and dementia onset or worsening, or bilateral infarctions in specified locations demonstrated on imaging results (Mayo Clinic criteria) had 75% sensitivity and 81% specificity for pure VaD (positive likelihood ratio, 3.9; 95% confidence interval, 2.2-6.7). Five cases of pure VaD lacked the temporal relationship and accounted for the imperfect sensitivity of the criteria. CONCLUSIONS: In this population-based autopsy study, the presence of vascular pathological characteristics in the absence of major AD pathological findings was common. Pure VaD without overt clinical strokes remains a challenge for antemortem diagnosis.     

Taste in mild cognitive impairment and Alzheimer’s disease

In this prospective study we investigated the quantitative and qualitative taste function of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). 29 healthy, elderly subjects, 29 MCI and 30 AD patients were tested using a validated taste test, the “taste strips”. Additionally, odor identification, odor discrimination, odor threshold, the mini-mental state examination (MMSE) and Apo E epsilon 4 status were examined. Regarding taste, there was a significant reduction of total taste scores and also the score for individual tastes on either side of the tongue between controls and MCI/AD patients. There was no significant difference in the taste scores between MCI and AD patients. A taste test may be a useful procedure for differentiating between healthy subjects and patients with MCI/AD in a clinical context. For diagnosing MCI versus AD, further tests such as smell test, MMSE, Apo E epsilon 4 status, FDG-PET and MRI appear to be useful.     

Cerebrospinal fluid matrix metalloproteinases and tissue inhibitor of metalloproteinases in combination with subcortical and cortical biomarkers in vascular dementia and Alzheimer's disease

Alzheimer's disease (AD) and vascular dementia (VaD) are intertwined by mixed dementia (MD) harboring varying degrees of AD pathology in combination with cerebrovascular disease. The aim was to assess whether there is a difference in the cerebrospinal fluid (CSF) profile, of selected proteins, between patients with VaD and MD with subcortical vascular disease (SVD), AD, and healthy controls that could contribute in the separation of the groups. The study included 30 controls, 26 SVD patients (9 VaD and 17 MD) and 30 AD patients. The protein panel included total tau (T-tau), hyperphosphorylated tau 181 (P-tau(181)), amyloid β 1-42 (Aβ(1-42)), neurofilament light (NF-L), myelin basic protein (MBP), heart fatty acid binding protein (H-FABP), matrix metalloproteinases (MMP-1, -2, -3, -9, and -10), and tissue inhibitors of metalloproteinases (TIMP-1 and -2). Immunochemical methods were utilized for quantification of the proteins in CSF and data analysis was performed with a multivariate discriminant algorithm. The concentrations of MBP, TIMP-1, P-tau(181), NF-L, T-tau, MMP-9, Aβ(1-42), and MMP-2 contributed the most to the separation between SVD and AD, with a sensitivity of 89% and a specificity of 90% (AUC = 0.92). MBP and NF-L performed the best in discriminating SVD from controls, while T-tau and Aβ(1-42) contributed the most in segregating AD from controls. The CSF biomarkers reflecting AD pathology (T-tau, P-tau(181), and Aβ(1-42)), white matter lesions (NF-L and MBP) and matrix remodeling (MMP-9 and TIMP-1) perform well in differentiating between SVD and AD patients.     

Screening for dementia: comparison of three commonly used instruments.

The sensitivity and specificity of three cognitive screening measures - the Mini-Mental State Exam (MMSE), Mattis Dementia Rating Scale (MDRS), and Neurobehavioral Cognitive Status Examination (NCSE) - were compared in a cohort of subjects with dementia as well as normal elderly individuals. Twenty-two patients met criteria for probable Alzheimer' s disease (AD), 19 for vascular dementia (VaD), and 12 were normal control subjects. The use of standard cutpoints resulted in poor to good classification accuracy for the three measures, but measurable improvement in sensitivity was obtained by adjusting the cutpoints for each measure. Discriminatory power was maximized with an MMSE cutpoint of < or = 26, an MDRS cutpoint of < or = 134, and requiring one or more NCSE subtests to be in the impaired range. Use of age and education adjusted norms resulted in good to excellent classification accuracy for the MMSE and MDRS. The NCSE subtest score pattern failed to differentiate between AD and VaD.