Frontal lobe degeneration of non-Alzheimer type. IV. White matter changes

The cerebral white matter in 16 cases of frontal lobe non-Alzheimer degeneration with dementia (FLD), four cases of Pick's disease and five age-matched controls was studied microscopically. All cases of dementia had white matter alterations, consisting of gliosis and loss of myelin, with a regional spread of changes that roughly corresponded with that of the cortical degeneration. The white matter changes were less severe than the cortical alterations, although the relative degree of severity between grey and white matter pathology varied from case to case. The white matter changes were in some respects similar in FLD and Pick's disease. They differed from those of other organic dementias. In FLD, they seem to be part of the histopathologic picture and to be secondary to the cortical degeneration.     

Frontal lobe degeneration of non-Alzheimer type. I. Neuropathology

Among 158 cases of organic dementia in a prospective study concerning both psychiatry and regional cerebral blood flow there were 26 cases with a mainly frontal or fronto-temporal dementia. Careful neuropathological investigation disclosed 20 cases of a mainly frontal or fronto-temporal grey matter degeneration, in four of them compatible with Pick's disease (2.5%) whereas 16 cases (10%) appeared to form a separate group without histological Alzheimer features and therefore named 'frontal lobe degeneration of non-Alzheimer type' (FLD). The remaining group of dementias of a clinically similar type proved to consist of cases of Jakob-Creutzfeldt's and Alzheimer's disease with frontal predominance and also a case of normal frontal cortex with a projected dysfunction caused by bilateral thalamic infarctions. Also other similar conditions are accounted for from the literature. The validity of the pathological changes described here, particularly with regard to their severity and regional distribution as well as their tendency to spare certain areas is attested by the clinical picture including neuropsychiatric symptoms and the regional cerebral blood flow pattern, both consistently producing the picture of a frontal and fronto-temporal disease of a progressive degenerative type. These features are dealt with in the following papers by Gustafson (1987) and Risberg (1987). FLD is in some morphological respects similar to other dementing disorders such as the ALS dementia complex and progressive subcortical gliosis, though with both clinical and clear-cut pathoanatomical differences. For the time being it seems safest to conclude that we are faced with a hitherto not fully recognized if not a new type of dementia caused by 'simple' neuronal degeneration of mainly the frontal or frontal and temporal lobes. It makes up about 10% of organic dementias, a figure that would be higher in purely clinical classifications due to the admixture of other frontal lobe disorders or frontally projected dysfunction clinically simulating FLD of the pathoanatomical type here described.     

Psychometric characteristics in patients with frontal lobe degeneration of non-Alzheimer type

Twenty patients, selected from a longitudinal study of patients with presenile and senile dementia, underwent psychometric assessment including semi-structured observations of behaviour in the test situation and examination for dysphasia. The patients were chosen on the basis of post-mortem investigation and showed frontal lobe degeneration (FLD) of non-Alzheimer type in 16 cases and Pick's disease in four cases. The patients are described with reference to cognition, language function, behaviour and emotional reactions in the test situation. The test results were analyzed and compared with psychometric results from other groups of demented patients, above all with Alzheimer's disease. The cognitive dysfunction was less severe in patients with onset of dementia below the age of 56 years as compared to patients with later onset, i.e., 56 years or older. Dysfunction of expressive speech was the most consistent finding in the patients with frontal lobe degeneration, while receptive speech functions were relatively less frequently affected.     

Presenile dementia combined with amyotrophy: a review of 34 Japanese cases

Thirty-four Japanese cases exhibiting presenile dementia combined with amyotrophy were reviewed with four case reports. The clinical feature of dementia was generally unspecific and could not be clearly diagnosed as Pick's disease or Alzheimer's disease. But most of these patients did not exhibit manifest visual agnosia or apraxia suggesting 'posterior dementia'. Brain CTs showed mild diffuse atrophy with non-circumscribed fronto-temporal accentuation. PSD (periodic synchronous discharge on EEG) as seen in Creutzfeldt-Jakob disease (CJD) was not noted in any of these cases. Although individual neurological findings were not contradictory to amyotrophy lateral sclerosis (ALS), the clinicopathologic findings, on the whole, could be regarded as indicative of an atypical spinal progressive muscular atrophy. The brain pathology lacked specific changes. A mild to moderate degree of glial proliferation, subcortical gliosis and a moderate spongy state of the upper cortical layers were seen mainly in the fronto-temporal area. Nigral degeneration was observed in half of the cases. No Pick's cells, Pick's balls, Alzheimer's neurofibrillary changes or senile plaques were observed except in two cases, in whom it could be regarded as physiological. Brain weight was lighter than that of normal Japanese but heavier than that of Pick's disease, Alzheimer's disease or CJD. The brain pathology was similar to that of progressive subcortical gliosis. We have concluded that the disease under discussion might be a new disease entity.     

Serum amyloid A in Alzheimer's disease brain is predominantly localized to myelin sheaths and axonal membrane.

Immunohistochemical localization of the injury specific apolipoprotein, acute phase serum amyloid A (A-apoSAA), was compared in brains of patients with neuropathologically confirmed Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD); Pick's disease (Pick's), dementia with Lewy bodies (DLB), coronary artery disease (CAD), and schizophrenia. Affected regions of both AD and MS brains showed intense staining for A-apoSAA in comparison to an unaffected region and non-AD/MS brains. The major site of A-apoSAA staining in both diseases was the myelin sheaths of axons in layers V and VI of affected cortex. A-apoSAA contains a cholesterol binding site near its amino terminus and is likely to have a high affinity for cholesterol-rich myelin. These findings, along with our recent evidence that A-apoSAA can inhibit lipid synthesis in vascular smooth muscle cells suggest that A-apoSAA plays a role in the neuronal loss and white matter damage occurring in AD and MS.     

Progressive subcortical gliosis of Neumann: a clinicopathologic study of two cases with review

A clinico-pathological report is given of two cases of progressive dementia of fronto-temporal type associated with variable cortical neuronal loss and extensive subcortical and deep white matter gliosis. There was minimal demyelination of white matter, significant gliosis of thalamus and inferior olivary nuclei. The authors review the condition of progressive subcortical gliosis, compare such changes with white matter changes in other dementias, examine the relationship to Kraepelin's disease, contrast the disorder with atypical Pick's dementia, progressive dementia with motor neuron disease and Creutzfeldt-Jakob dementia.     

Gallyas-Braak银染法在神经系统变性疾病中的应用

目的 评估Gallyas-Braak银染色方法在几种神经系统变性疾病病理诊断中的作用和价值。方法 采用修订Gallyas-Braak染色法,对经临床和常规病理方法诊断的22例神经系统变性病的脑和脊髓标本进行了回顾性研究。结果 Gallyas-Braak银染色可良好显示Alzheimer病（AD）,其他变性病痴呆,正常老年人的海马及额、颞叶皮层神经原纤维缠结,且较Bodian染色清楚。在4例有痴呆症状和明显锥体外体征患者的中脑,基底节观察到大量神经元球形团样缠结,同时在运动皮层,基底节,中脑观察到星形细胞丛状缠结,其中2例符合进行性核上性麻痹的病理诊断标准,另2例观察到运动皮层和基底节区星形细胞斑,加之皮层神经元气球样变,符合皮质基底节变性的病理特征。3例多系统萎缩的脑和脊髓白质显示广泛分布少突胶质细胞包涵体。1例AD病的颞叶和海马皮质2－3层神经毡内显示嗜银颗粒,而Bodian染色未观察到这些病理改变。结论 Gallyas-Braak染色除显示神经原纤维缠结外,还能较好显示胶质细胞变性和神经毡异常结构,因此对进行性核上性麻痹,皮质基底节变性,多系统萎缩,嗜银颗粒病的病理诊断有重要价值。     

Pick's disease. A special type of pathological aging of the brain

Pick's disease (circumscribed lobar atrophy of the brain) in its typical form, is a so-called presenile type of dementia, i.e. a cerebral disease which begins in the sixth decade of life, and leads to a progressive loss of intellectual capacity traits. Neuropathologically, Pick's disease is characterised by severe focal atrophy of the cerebral cortex, mainly of basal parts of the temporal and frontal lobe. In the long run, all the nerve cells of the affected areas and their processes are destroyed. This also involves the subcortical white matter (loss of nerve fibres and cicatrisation). Concomitant atrophies of other parts of the brain are frequent. The article reports on the results of the clinico-neuropathological examination of 30 cases of Pick's disease basing on the author's own observations. Special emphasis is placed on "neuronal atrophising dystrophy" of cortical systems as a characteristic change caused by Pick's disease; this phenomenon is interpreted as an endogenous disturbance of the neuronal structural metabolism. This process is, as a matter of principle, identical with the physiological "atrophising dystrophy" which represents part of cerebral aging. There are also pathogenetical parallels to orthological neuronal reactions to damaging of the axis cylinder processes. Pick's disease is characterised by the pathological extent and type of manifestation of "neuronal atrophising dystrophy". This pathological distortion of physiological processes is probably due to a specifically genetic and sometimes hereditary constellation. Finally, the article discusses the functional neuropathology or neuropsychology of Pick's disease. The importance of the basal temporofrontal cortex for the quality and preservation of human personality is emphasised; the changes of the high-class performances of the human brain, as caused by Pick's disease, are interpreted. Referring to the peculiarities of Pick's disease compared with normal cerebral aging, particular attention is drawn to the concept of "disease" and the definition of senile cerebral aging.     

The role of routine laboratory studies and neuroimaging in the diagnosis of dementia: a clinicopathological study

OBJECTIVE: To determine the neuropathological diagnoses of longitudinally followed patients with potentially reversible causes of dementia and to examine the results of the "dementia work-up," especially neuroimaging, by comparison with the pathological diagnosis. DESIGN: A neuropathologic series of 61 consecutive patients, with review of clinical, laboratory, neuroimaging, and pathological results. RESULTS: Of the 61 patients, forty-eight (79%) had a clinical diagnosis of probable or possible Alzheimer's disease (AD). Compared with the pathological diagnosis, the sensitivity and specificity of the clinical diagnosis of AD were 96% and 79%, respectively. Of the 61 patients, 9 had abnormal laboratory tests, the correction of which did not improve the subsequent course. These patients were found to have AD8 and frontotemporal dementia on pathology. In two patients, neuroimaging was helpful in the clinical diagnoses of frontotemporal dementia and progressive supranuclear palsy (PSP). Neuroimaging revealed cerebrovascular disease in 18 patients, only two of whom were suspected clinically. Pathology confirmed AD in 17 and PSP in 1 of these patients. Sensitivity and specificity for the clinical diagnosis of cerebrovascular disease in comparison with pathology were 6% and 98%, respectively. With the added information from neuroimaging, that sensitivity increased to 59% and specificity decreased to 81%. CONCLUSIONS: All cases with abnormal laboratory or neuroimaging results had AD or some other neurodegenerative disease on pathology. The "dementia work-up" did not reveal any reversible causes for dementia in this group of patients. Neuroimaging may have a role, especially in the diagnosis of possible AD with concomitant cerebrovascular disease.     

383例老年人尸检资料中痴呆的病因分析

目的分析经尸检证实的老年人痴呆原因,提高对老年期痴呆各种病因的认识。方法对383例≥60岁有脑病理检查的患者进行临床和病理资料回顾性分析。结果383例老年人尸检病例中,有临床病史和相关病理改变的痴呆患者78例,痴呆发生率为20．4％。其中血管性痴呆30例,占老年人痴呆病例的38．5％;变性病痴呆20例,占25．6％,其中阿尔茨海默病11例,路易体痴呆、皮质基底节变性、进行性核上性麻痹、皮克病、帕金森病合并痴呆等非阿尔茨海默病型痴呆共9例;各种内科疾病包括肝性脑病、肺性脑病、低血糖反复发作引起认知功能障碍共16例,占老年人痴呆的20．5％。另外还有脑肿瘤、正常颅压脑积水和慢性硬膜下血肿等疾患共12例占15．4％。结论老年期痴呆是多病因所至的临床综合征,应该重视临床病史和现有的辅助检查方法对痴呆病因诊断的作用。     

Other neurologic diseases with dementia as a sequela

Less-common causes of dementia are briefly discussed. Disorders covered include Pick's disease, primary progressive aphasia, progressive supranuclear palsy, Huntington's disease, olivopontocerebellar atrophies, closed head injury, dementia pugilistica, and Creutzfeldt-Jakob disease. Pseudodementia is also discussed. These disorders are compared and contrasted with the more common etiologies of dementia that are reviewed in other articles in the issue. Topics covered include treatment, differential diagnosis, clinical features, and pathogenesis.     

Some cerebral proteins and enzyme systems in Alzheimer's presenile and senile dementia.

The water-soluble proteins of the cerebral gray matter and some enzyme systems (cholinesterase, acetylcholinesterase, lactate dehydrogenase, malate dehydrogenase, acid phosphatase) were studied in 9 autopsy cases of Alzheimer's presenile or senile dementia, 1 case of Pick's disease and 1 case of cerebral arteriosclerosis. The proteins and enzyme patterns were visualized on polyacrylamide gradient gels after electrophoresis. In all patients studied, the profiles of cerebral gray-matter proteins were normal. In the patients with advanced dementia, the enzyme patterns usually were abnormal. Particularly in Alzheimer's disease, the activity of malate dehydrogenase was markedly increased.     

Is dementia a disease?

BACKGROUND: It is customary for many neurologists to think that dementia is a disease. This view is based on the following reasons: (1) a brain disease is the cause of cognitive impairment; (2) therefore, such cognitive impairment is substituted for the disease, becoming dementia, which is then also regarded as a mental disease. OBJECTIVE: In this brief article, I take exception to such a view, contrary to the common belief in the medical field, on the ground that senile plaques and/or neurofibrillary tangles or any other factors cause neuronal apoptosis but they do not cause dementia directly. METHODS: Literature on dementia and aphasia are critically and briefly reviewed to get the historical perspective that it is the progressive neuronal losses, losing brain functions as a result, that cause dementia; that is, brain diseases cause neuronal losses which then result in the decrease of brain functions, thereby leading to dementia. RESULTS: There is no direct cause-effect relationship between brain disease, be it caused by vascular factors or not, and dementia which is the consequence or sequela of neuronal losses. CONCLUSIONS: It is concluded that dementia is not a disease and yet it occurs not only in Parkinson's disease, Alzheimer's disease (AD), Huntington's disease and Pick's disease, but also in any other neurodegenerative disease, e.g., spinocerebellar ataxia, or vascular disease, e.g., Binswanger's disease, as part of the process of aging; in fact, AD is now regarded by some as a vascular disorder with neurodegenerative consequence, rather than a neurodegenerative disorder with vascular consequence. But vascular disorder is misleading if AD includes both neurofibrillary tangles and senile plaques; on the other hand, AD cannot be a vascular disorder if it includes only neurofibrillary tangles, as it should. Dementia, in this context, is re-defined as the differential manifestation of deteriorating brain functions over time as a part of aging due to cell deaths in the brain caused by any neurodegenerative disease. Its prominent symptoms are language disorders which must be distinguished from aphasias. It is also suggested that in fairness to Fischer, senile plaques be designated as Fischer's disease separate from neurofibrillary tangles for which AD was originally named as an eponym.     

Incidence of dementia,Alzheimer's disease,and vascular dementia in Italy. The ILSA Study

OBJECTIVES: To estimate the incidence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in older Italians and evaluate the relationship of age, gender, and education to developing dementia. DESIGN: Cohort incidence study in the context of the Italian Longitudinal Study on Aging. SETTING: Population sample from eight Italian municipalities. PARTICIPANTS: A dementia-free cohort of 3,208 individuals (aged 65-84), individuated after a baseline evaluation performed in 1992 / 93, aimed at detecting prevalent cases. MEASUREMENTS: The dementia-free cohort was reexamined in 1995 to identify incident cases. The Mini-Mental State Examination (cutoff 23 / 24) was employed to screen for dementia. Trained neurologists evaluated the individuals who screened positive. Final diagnoses had to meet Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria for dementia, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD, and International Classification of Diseases, Tenth Revision criteria for VaD. RESULTS: Before the follow-up examination, 382 individuals had died (232 had reliable information). Of the 2,826 survivors, 2,266 completed the study. Overall, 127 new dementia cases were identified. Average incidence rates per 1,000 person-years were 12.47 (95% confidence interval (CI)=10.23-14.72) for dementia, 6.55 (95% CI=4.92-8.17) for AD, and 3.30 (95% CI=2.14-4.45) for VaD. Both AD and VaD showed age-dependent patterns. Education was protective against dementia and AD. Women carried a significantly higher risk of developing AD (hazard ratio=1.67, 95% CI=1.02-2.75), and men of developing VaD (hazard ratio=2.23, 95% CI=1.06-4.71). CONCLUSIONS: Incidence of dementia in Italy paralleled that in most industrialized countries. About 150,000 new cases per year are expected. A significant gender effect was evidenced for major dementia subtypes. The burden of VaD, especially in men, offers opportunities for prevention.     

A neuropathological study of dementia in nursing homes in Shimane prefecture, Japan: evaluation of the age and gender effect.

BACKGROUND: Vascular dementia (VD) has been held responsible for the majority of all dementia cases in both epidemiological and neuropathological studies in Japan. The aim of this study was to clarify relative frequencies of dementia neuropathologically in Japanese nursing home residents over a 17-year period and to clarify the gender and age effect on the relative frequencies. METHODS: Three hundred ten aged nursing home residents (146 men and 164 women), including dementia cases in Shimane prefecture, Japan, were evaluated clinically and neuropathologically over a period of 17 years. RESULTS: One hundred twenty-two (48 men and 74 women) of the 310 autopsied (39%) had shown signs of dementia during their lives. In classifying dementia type, Alzheimer's disease (AD) accounted for 34% (41); VD 35% (42); mixed dementia 11% (14); and "other" dementia 20% (25) of all samples. As to the gender and age effect, the most characteristic findings were as follows: (a) There were only VD cases in the 57-69-year-old group; (b) the 70-79 male age group lacked any cases with only AD; (c) more AD than VD was found in elderly men; and (d) in women, AD was the major cause of dementia in total. CONCLUSIONS: VD is responsible for the major cause of dementia in the younger women and the men under 90 years of age; AD is the leading cause of dementia in the elderly men and the women over 79 years of age in nursing homes, Shimane prefecture, Japan.     

Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series.

OBJECTIVES: Most clinico-neuropathological correlative studies of Alzheimer's Disease (AD) are based on research cohorts that are not necessarily generalizable to patients seen in the general medical community. In this study, we examine the accuracy of the criteria used in diagnosing AD in a community-based case series of patients with memory complaints. DESIGN AND PARTICIPANTS: Clinical and neuropathological diagnoses were obtained from 134 patients evaluated for dementia who subsequently underwent autopsy. SETTING: Subjects who exhibited new symptoms of dementia and were enrolled in the University of Washington/Group Health Cooperative Alzheimer's Disease Patient Registry were eligible for this study. MEASUREMENTS: Clinico-pathological correlation was performed using NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. RESULTS: Ninety-five of the 134 cases studied met CERAD neuropathological criteria for AD. The sensitivity of NINCDS-ADRDA "probable AD" was 83% (diagnosing AD correctly) and overall clinical diagnostic accuracy was 75%. However, there was a high rate of additional neuropathological findings. Only 34 of the 94 cases had pure AD on neuropathology, whereas the remainder frequently had coexisting vascular or Parkinson's disease lesions. CONCLUSIONS: This study of a large series of community-based incident dementia cases provides a way of judging the adequacy of currently available clinical diagnostic criteria. It also shows that co-existing neuropathological findings are common in community-based AD.     

Induction of complement C9 messenger RNAs in human neuronal cells by inflammatory stimuli: relevance to neurodegenerative disorders

Neurons express proteins of the classical complement pathway, including C9. Both the mRNA and protein levels for C9 are sharply upregulated in brain areas affected by Alzheimer's disease (AD). Since little is known about the signals that are responsible for this upregulation, we evaluated in human SH-SY5Y neuroblastoma cells the factors which stimulate C9 production. Interferon-gamma, phorbol myristate acetate and interleukin-6 all stimulated C9 mRNA expression but the inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, as well as the anaphylatoxin C5a and the bacterial lipopolysaccharide, were ineffective. Immunohistochemical analysis of postmortem human brains for C9 protein demonstrated its presence in many cortical pyramidal neurons in AD, Down's syndrome, the parkinsonism dementia complex of Guam and pallido-ponto-nigral degeneration, as well as in thalamic neurons of progressive supranuclear palsy and ballooned neurons of Pick's disease. Since C9 is required for the membrane attack complex of complement to become functional, interfering with signaling pathways that stimulate its production could offer new therapeutic strategies for treating various neurodegenerative disorders.     

Rapid detection of apolipoprotein E genotypes in Alzheimer's disease using polymerase chain reaction-single strand conformation polymorphism

Apolipoprotein E (APOE) gene on chromosome 19q13.2 is encoded by three common alleles designated as epsilon2, epsilon3 and epsilon4. In Alzheimer's disease (AD) the epsilon4 allele is over-represented and is considered to be a major genetic risk factor. Several methods have been developed to determine APOE genotypes. Among them, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) appears to be highly reliable. In this study, we improved the nonisotopic PCR-SSCP method for determining APOE genotypes in 42 cases of AD patients, 40 cases of non-AD dementia patients, and 49 cases of age-matched controls. DNA from the target sequence on APOE was amplified by PCR from peripheral blood genomic DNA. PCR products were electrophoresed in a non-denaturing polyacrylamide gel and visualized by silver staining. We found that the epsilon4 allele had a significantly high frequency of occurrence in AD patients (33.3%) compared with age-matched controls (13.3%) (chi(2) = 10.43, p = 0.001) and non-AD dementia (10%) (chi(2) = 13.02, p<0.001) whereas the epsilon3 allele was of high frequency in non-AD dementia (90%) compared with age-matched controls (85.7%) and AD patients (66.7%). APOE epsilon4 homozygotes were found only in AD groups. On the other hand, the epsilon2 allele was found only in an age-matched control. This study confirmed that the APOE psilon4 allele is a risk factor in Thai AD subjects and that the PCR-SSCP method is a rapid and useful means of detecting the APOE genotype in AD.     

Evaluation of respiratory chain activity in lymphocytes of patients with Alzheimer disease

Alzheimer disease (AD) is a progressive neurodegenerative disease associated with cognitive impairment in multiple domains, such as memory and executive functions. Studies reveal damage in the electron transport chain of patients with AD, suggesting that this mitochondrial dysfunction plays an important role in the pathophysiology of the disease. Blood samples were taken from patients with AD (n?=?20) and older subjects without dementia (n?=?40) to evaluate the activity of complexes I, II, II-III, and IV of the mitochondrial respiratory chain in isolated lymphocytes. Results from the patient and control groups were compared. The activity of complexes II and IV was increased among patients compared to the control group. No significant difference was observed between controls who were not using psychotropic medication and patients. Our findings point out a mechanism of cellular compensation in which the mitochondrial respiratory chain requires an increase in electron transport to supply the energy needed for cellular functioning. Additional studies are needed to better clarify the mechanisms involved in the mitochondrial dynamics of AD.     

血清SAA、sNFL水平对老年阿尔茨海默病的预测价值分析

目的探讨血清淀粉样蛋白A（SAA）、血清神经丝蛋白轻链（sNFL）水平对老年阿尔茨海默病（AD）的预测价值。 方法选取亳州市人民医院神经内科自2016年5月至2021年5月收治的147例具有AD危险因素的老年患者为研究组，另选取同期128例老年健康体检者（认知功能正常）为对照组，均行SAA、sNFL水平检测并对比。对研究组患者进行随访，观察其进展为AD的情况，并据此将其分为进展组与未进展组，对比SAA、sNFL水平，且采用受试者工作特征（ROC）曲线分析SAA、sNFL水平单项及联合对老年AD的预测价值。 结果研究组SAA、sNFL水平高于对照组，差异具有统计学意义（P<0.05）。随访1~5（2.65±0.67）年，147例老年患者中进展为AD的有39例（进展组），进展率为26.53%。进展组SAA、sNFL水平均高于未进展组，差异具有统计学意义（P<0.05）。147例老年患者中5年后随访到8例，队列保持率为5.44%，其中随访5年进展为AD的有3例，未进展为AD的有5例。ROC结果显示，SAA、sNFL联合预测AD的灵敏度均高于单独预测（P<0.05），曲线下面积也高于单独预测（P<0.05），特异度与单独预测比较差异无统计学意义（P>0.05）。 结论SAA、sNFL水平在AD患者中较非AD者升高，且均对AD具有一定预测价值，但二者联合预测价值更高。