Early diagnosis of Alzheimer dementia based on clinical and biological factors

Alzheimer's disease (AD) is common in elderly individuals; it causes distress for the patients and their relatives as well as large costs for the society. With the advent of symptomatic treatment at present and probable etiology-based cures in the future, it will be possible to relieve and put an end to these negative effects. Therefore, it is necessary to diagnose the disease as early as possible. In this review, we briefly summarize the state-of-the-art concerning various available clinical and biochemical methods for identifying AD. Increasing age, heritage, and presence of ApoE e4 allele have been confirmed as risk factors for AD as well as some putative factors (e.g., low education, hypertension, hypotension) based on epidemiological recent research. Selective impairment of episodic memory has been found to be a preclinical marker for future development of AD based on convergent data from asymptomatic AD-related mutation carriers, longitudinal studies of patients with mild cognitive impairment (MCI), and epidemiological studies of incident AD cases. Neurophysiological methods are inexpensive and useful for the identification of changes in brain dysfunction in AD and new promising methods are under development. Using magnetic resonance imaging (MRT), structural measurements of brain atrophy and specific brain structures such as the hippocampus have been reported to detect dementia development early in the course of disease. Similarly, functional measurements of brain activity (e.g., blood flow) have revealed that hypometabolism in bilateral parietotemporal brain areas early in the disease course. Finally, biochemical studies have demonstrated that certain proteins (e.g., tau the A beta 1-42/43 metabolite of the amyloid precursor protein) may be associated with the disease process in AD, although the specificity of these markers remains to be established. It is concluded that still no single marker of AD exists, which makes it necessary to rely on data from multiple sources in order to arrive at the best possible diagnosis of AD.     

Neuropathologic validation of clinical diagnosis of senile dementia of the Alzheimer type]

The purpose of this work was to establish a neuropathological confirmation of the clinical diagnosis of senile dementia of the Alzheimer type (SDAT) in a group of patients prospectively studied in a geriatric hospital since 1984 (Charles Richet Study). The sample consisted of 45 cases, 35 of which had received a clinical diagnosis of SDAT and 10 others a diagnosis of either vascular or mixed dementia. The mean age at death was 85 +/- 6.9 years (range 64-97). The neuropathological diagnosis was established independently of the clinical findings. Senile lesions typical of SDAT were found in 32/35 cases, giving a 91.4% rate of clinico-pathologic agreement. However, vascular lesions were present in 10 cases (28.5%) and the final pathologic diagnosis was mixed dementia, lowering the score of agreement for SDAT to 63%. Considering that the pathological criteria for the diagnosis of SDAT are not uniform, we independently applied 3 inclusion (senile lesions) and 3 exclusion (vascular lesions) criteria for the diagnosis of SDAT to each of the 45 cases. This permitted a comparison of nine combinations of neuropathological criteria with the clinical diagnosis. The sensitivity values ranged from 37 to 80% and the specificity values ranged from 55 to 100%. The highest agreement rate with the clinical diagnosis was achieved when were associated the criterion which specified that plaques and tangles must be present in the hippocampus regardless of neocortical findings and the criterion which excluded cases with vascular lesions of any site if their volume was 50 ml or more.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of factors of importance for clinical dementia diagnosis

Diagnosing clinical dementia is based on an assessment of different variables, such as the patient's medical history, known risk factors, and biochemical features. Partial least squares discriminant analysis was used to evaluate variables of importance for diagnosing dementia in a clinical dementia population. Polymorphism for genotypes of glutathione S-transferase (GST) and sulfotransferase 1A1, hypothetically of importance in dementia disorders, was also included in the analysis. The study population consisted of 73 patients with Alzheimer's disease (AD), 14 with mixed dementia, 75 patients with vascular dementia, and 28 control cases. We found that several of the variables, such as the presence of ApoE4 allele, high cerebrospinal fluid levels of total tau protein, low levels of beta-amyloid((1-42)), and a low score on the Mini-Mental State Examination, facilitated a discrimination between the diagnoses compared with the controls. The different diagnoses overlapped. There were indications that genotypes of GSTs contributed to a subgrouping within AD.     

阿尔茨海默病的早期诊断与治疗

老年性痴呆（又称阿尔茨海默病，Alzheimer disease，AD）是一种以认知功能减退、生活功能下降及精神行为异常为临床表现的神经系统退行性疾病，随着老龄人口的增加，痴呆的患病率逐年增加。根据Zhang等在1997--1998年对我国部分城市的流行病学调查，在55岁及以上的人群中，AD患病率为2．1％（732／34807）。围绕AD的发病机制，     

临床前期阿尔茨海默症的早期诊断与干预

随着人口老龄化的加剧,以阿尔茨海默病（Alzheimer Disease,AD）为主的老年认知障碍问题日趋严重.作为一种多因素、多阶段并有伴随疾病的临床综合征,老年认知障碍在临床症状出现后将进展成不可逆性痴呆.因此,在无症状性临床前期AD症（PCAD）阶段进行早期诊断与干预成为了国内外研究的热点.现对PCAD的危险因素和针对其诊断干预的探索性研究进行综述,试图寻找在早期病理进程中新的可用于临床早期诊断的生物标记物及早期干预的药物靶点.     

Early diagnosis of dementia: neuroimaging

The use of neuroimaging is reviewed in the diagnosis of dementia, especially Alzheimer’s disease (AD). Computed tomography (CT) may be used to exclude other causes of dementia than AD. The finding of cortical or subcortical atrophy on CT or magnetic resonance imaging (MRI) itself does not indicate AD. Hippocampal atrophy on CT/MRI provides a useful early marker, although further longitudinal and neuropathological study is required. CT- and MRI-based measurements of hippocampal atrophy show promise in providing useful diagnostic information for discriminating patients with probable AD from normal elderly individuals. Using a standardized imaging protocol, including some assessment of hippocampal atrophy, can save costs since patients with suspected AD must undergo a cross-sectional imaging study to exclude other (treatable) causes of dementia. Combining an assessment of hippocampal atrophy with cerebral blood flow measurements by single photon emission computed tomography is not warranted either from a clinical or from an economic point of view. Received: 4 November 1997 Accepted: 23 July 1998     

Early diagnosis of dementia: neuropsychology

Neuropsychology contributes greatly to the diagnosis of dementia. Cognitive deficits can be detected several years before the clinical diagnosis of dementia. The neuropsychological profile may indicate the underlying neuropathology. Neuropsychological assessment at an early stage of dementia has two goals: (a) to determine a memory disorder, not always associated with a memory complaint, and (b) to characterize the memory disorder in light of the cognitive neuropsychology and to assess other cognitive (and noncognitive) functions toward integrating the memory disorder in a syndrome. We review the global tools, the memory tests that describe the memory profile and indicate the underlying pathology, the assessment of other cognitive functions, and the neuropsychological patterns of typical Alzheimer’s disease, frontotemporal dementia, primary progressive aphasia, semantic dementia, Lewy body dementia, subcortical dementia, and vascular dementia. These patterns must be interpreted in the light of the history, rate of progression, imaging results, and nature of existing behavioral disturbances. Moreover, there may be overlap between two or more pathologies, which complicates the diagnostic process. Follow-up of patients is necessary to improve diagnostic accuracy. Received: 20 July 1998 Accepted: 23 July 1998     

脑脊液生物学标志物诊断阿尔茨海默病与血管性痴呆

目的探讨脑脊液β-淀粉样蛋白（Aβ1～42）、tau蛋白和磷酸化tau蛋白诊断阿尔茨海默病与血管性痴呆的敏感性和特异性。方法采用酶联免疫吸附法检测阿尔茨海默病与血管性痴呆患者脑脊液中Aβ1～42、tau蛋白和磷酸化tau蛋白浓度的变化,根据受试者工作特征曲线观察脑脊液中这3种生物学标志物用于诊断阿尔茨海默病与血管性痴呆的敏感性和特异性;采用单因素方差分析以及受试者工作特征曲线对所获结果进行统计学分析。结果阿尔茨海默病组患者脑脊液Aβ1～42浓度低于对照组（P=0.010）,tau蛋白浓度高于对照组（P=0.001）和血管性痴呆组（P=0.030）,磷酸化tau蛋白浓度高于对照组（P=0.004）。脑脊液Aβ1～42、tau蛋白和磷酸化tau蛋白用于诊断阿尔茨海默病的敏感度为60.00%～96.70%,特异度可达70.00%～90.00%。Aβ1～42、tau蛋白和磷酸化tau蛋白联合检测可提高阿尔茨海默病与血管性痴呆鉴别诊断的敏感性和特异性,敏感度可达86.57%,特异度为90.00%。结论脑脊液Aβ1～42、tau蛋白和磷酸化tau蛋白浓度的变化,不仅对诊断阿尔茨海默病具有较高的敏感性和特异性,而且亦可作为阿尔茨海默病与血管性痴呆鉴别诊断的生物学指标。     

Delusional depression as differential dementia of the Alzheimer type diagnosis

For several years, a 68-year-old patient had been treated for a dementia of Alzheimer's type and finally admitted to a closed gerontopsychiatric nursing home. According to information from his relatives, he first developed psychotic symptoms 3 years prior to admission in our psychiatric department. Several months later, he developed a lack of drive, lack of interests, and reduced emotional reaction. After a standard diagnostic work-up (psychiatric, neurological, and general medical examination, CSF examination, laboratory analyses, cranial computerized tomography), we began electroconvulsive therapy (ECT) with a working hypothesis of major depression with psychotic symptoms. The ECT was able to ameliorate rapidly the psychiatric status of the patient. After 10 weeks of inpatient treatment, he could be discharged from the hospital and was able to take up his usual professional activities on a voluntary basis. This article describes the need for an early differential diagnosis of dementias. Standardized and differential diagnoses of dementias are necessary for an antidementive therapy as well as for the detection of potentially curable diseases.     

Frontal assessment battery and differential diagnosis of frontotemporal dementia and Alzheimer disease

BACKGROUND: The different distribution of pathologic features in frontotemporal dementia (FTD) and Alzheimer disease (AD) predicts a predominant dysexecutive syndrome in FTD. The Frontal Assessment Battery (FAB) has previously been validated in diseases associated with a frontal lobe dysfunction. OBJECTIVE: To evaluate the sensitivity of the FAB to differentiate FTD and AD. DESIGN: Comparison study. SETTING: Memory Clinic of the Salpêtrière Hospital, Paris, France. PATIENTS: Twenty-six patients with FTD and 64 patients with AD. MAIN OUTCOME MEASURES: Comparison of FAB and Mini-Mental State Examination (MMSE) scores between patients with FTD and those with AD. RESULTS: The mean +/- SD FAB scores significantly differed between patients with FTD (7.6 +/- 4.2) and those with AD (12.6 +/- 3.7) (P<.001), but not MMSE scores. The FAB correctly identified 78.9% of the patients. These results were maintained in a subgroup of mildly demented patients (MMSE score, > or =24). In these patients, a cutoff score of 12 on the FAB was optimal to differentiate both disorders (sensitivity, 77%; specificity, 87%). CONCLUSIONS: The FAB takes less than 10 minutes to administer and provides an objective measure to distinguish FTD from AD in mildly demented patients.     

Alzheimer病的病理与临床诊断

对生前经过痴呆调查与临床诊断的９例老人院住院老人死亡后进行尸解神经病理学观察。结果发现９例尸检脑均有不同程度的萎缩与锥全细胞减少，脂褐素沉积，胶质细胞增生，淀粉样小体存在。其中３例尚在皮层与海在量老年斑（ＳＰｓ）与神经原纤维缠结（ＮＴＦｓ），病理确诊为Ａｌａｈｅｉｍｅｒ病（ＡＤ）；其余６例明确为非Ａｌｚｈｅｉｍｅｒ病老年脑（ＮＡＤ）。该病理结果与临床诊断全部痊愈，提示ＮＩＮＣＤＳ－ＡＤＲＤＡ之ＡＤ     

Alois Alzheimer on presenile dementia

The work of Alois Alzheimer on presenile dementia is a landmark in the history of psychiatry not fully appreciated by contemporary psychiatrists. In this paper, the history of his landmark work is reviewed in the context of the growing importance of psychiatric involvement in Alzheimer's disease. Annotated excerpts from Alzheimer's second paper (1911), never before translated into English, are presented. The historical significance of Alzheimer's findings vis-a-vis Kraepelinian psychiatry and the relationship of his investigations to modern psychiatric research in primary degenerative dementia of the Alzheimer type are discussed.     

阿尔茨海默病和血管性痴呆的临床症状研究

目的：了解阿尔茨海默病(AD)和血管性痴呆(VD)患者不同严重程度痴呆时临床症状。方法：认知功能测试量表采用简易智力状态检查(MMSE)、日常生活活动能力量表(ADL)，精神行为症状采用汉密尔顿抑郁量表(HAMD)、老年临床评定量表(SCAG)对住院AD157例及VD150例进行测试。结果：两组患者有不同程度的认知功能障碍及精神行为症状。AD组患者认知功能较差，VD组患者躯体生活自理较差。结论：不同严重程度的AD和VD患者临床症状有差异。