The decline and resurgence of vascular dementia.

Arteriosclerotic narrowing of cerebral arteries was once viewed as the key to mental decline. As Alzheimer''s disease gained recognition and the concept of multi-infarct dementia achieved acceptance, vascular dementia came to be regarded as uncommon. The changing nature of cerebral vascular disease, the aging of the population and the widespread use of brain imaging techniques have brought new prominence to vascular dementia, chiefly in the form of an epidemic of "Binswanger''s disease". Growing evidence suggests that not only grey matter lesions but also white matter lesions contribute to dementia, that vascular factors commonly coexist and interact with Alzheimer changes and that Alzheimer''s disease has a vascular and potentially treatable component. Vascular dementia needs to be redefined, reappraised and reinvestigated.     

Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: population based study.

OBJECTIVE--To determine the association between the e4 allele of apolipoprotein E and Alzheimer''s disease in a randomly selected population sample. DESIGN--Cross sectional population based study. SUBJECTS--980 people aged 69 to 78 (349 men, 631 women). SETTING--Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES--Presence of e4 allele and diagnosis of Alzheimer''s disease by detailed neurological and neurophysiological evaluation. RESULTS--46 (4.7%) subjects were classified as having probable or possible Alzheimer''s disease. The frequency of the apolipoprotein E e4 allele was 0.359 in patients with Alzheimer''s disease and 0.165 subjects without dementia (P < 0.0001). The prevalence of Alzheimer''s disease was 2.9% in subjects with no e4 alleles, 7.6% in subjects with one e4 allele, and 21.4% in subjects with two e4 alleles of apolipoprotein E. CONCLUSIONS--Allele e4 of apolipoprotein is associated with Alzheimer''s disease in a dose-response fashion in a randomly selected elderly population.     

Diagnosing dementia: do we get it right?

To find out whether the diagnosis of dementia agreed with findings at necropsy a detailed assessment of 27 elderly patients (mean age 82 (range 70-94] presenting with dementia was conducted at a combined department of geriatric medicine and psychiatry for the elderly. On the basis of the results the cause of the dementia was diagnosed clinically. Neuropathological examinations were performed after death. The clinical diagnosis made during life was not supported by the findings at necropsy in 11 cases. Alzheimer''s disease was overdiagnosed in life (13 cases, of which only six were confirmed at necropsy). Although the clinical investigation was limited by availability of resources, neither cranial computed tomography nor the Hachinski score helped to distinguish between multi-infarct dementia and Alzheimer''s disease in this age group. This study confirms the value of neuropathological studies in the precise diagnosis of dementia.     

Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study.

OBJECTIVE--To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. DESIGN--Population based cross sectional study. SETTING--Ommoord, a suburb of Rotterdam. SUBJECTS--7528 participants of the Rotterdam study aged 55-106 years. RESULTS--474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimer''s disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinson''s disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. CONCLUSIONS--The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimer''s disease. In this study an inverse dose-response relation was found between education and dementia--in particular, Alzheimer''s disease.     

Relation between severity of Alzheimer's disease and costs of caring

BACKGROUND: Data from the Canadian Study of Health and Aging (CSHA) were used to examine the relation between severity of Alzheimer''s disease, as measured by the Mini-Mental State Examination (MMSE), and costs of caring. METHODS: The CSHA was a community-based survey of the prevalence of dementia, including subtypes such as Alzheimer''s disease, among elderly Canadians. Survey subjects with a diagnosis of possible or probable Alzheimer''s disease were grouped into disease severity levels of mild (MMSE score 21-26), mild to moderate (MMSE score 15-20), moderate (MMSE score 10-14) and severe (MMSE score below 10). Components of care available from the CSHA were use of nursing home care, use of medications, use of community support services by caregivers and unpaid caregiver time. Costs were calculated from a societal perspective and are expressed in 1996 Canadian dollars. RESULTS: The annual societal cost of care per patient increased significantly with severity of Alzheimer''s disease. The cost per patient was estimated to be $9451 for mild disease, $16,054 for mild to moderate disease, $25,724 for moderate disease and $36,794 for severe disease. Institutionalization was the largest component of cost, accounting for as much as 84% of the cost for people with severe disease. For subjects living in the community, unpaid caregiver time and use of community services were the greatest components of cost and increased with disease severity. INTERPRETATION: The societal cost of care of Alzheimer''s disease increases drastically with increasing disease severity. Institutionalization is responsible for the largest cost component.     

Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study

ObjectivesTo evaluate a simple three step procedure to identify people in the general population who are in the preclinical phase of Alzheimer''s disease and dementia.DesignThree year population based cohort study.SettingKungsholmen cohort, Stockholm, Sweden.Participants1435 people aged 75-95 years without dementia.AssessmentsSingle question asking about memory complaints, assessment by mini-mental state examination, and neuropsychological testing.ResultsNone of the three instruments was sufficiently predictive of Alzheimer''s disease and dementia when administered separately. After participants had been screened for memory complaints and global cognitive impairment, specific tests of word recall and verbal fluency had positive predictive values for dementia of 85-100% (95% confidence intervals range from 62% to 100%). However, only 18% of future dementia cases were identified in the preclinical phase by this three step procedure. Memory complaints were the most sensitive indicator of Alzheimer''s disease and dementia in the whole population, but only half the future dementia cases reported memory problems three years before diagnosis.ConclusionThis three step procedure, which simulates what might occur in clinical practice, has a high positive predictive value for dementia, although only a small number of future cases can be identified.

What is already known on this topic

Alzheimer''s disease is characterised by a preclinical phase, during which cognitive deficits are seen before diagnosisElderly people with subjective memory complaints and objective global cognitive impairment have a high risk of developing Alzheimer''s disease and dementia

What this study adds

This three step procedure (self report of memory complaints, test of global cognitive functioning, and then domain specific cognitive tests) has a positive predictivity of 85-100% for Alzheimer''s disease and dementia at three yearsHowever, only 18% of people in the preclinical phase can be identified using this procedureAbout half of the people in the preclinical phase of Alzheimer''s disease and dementia do not report problems with their memory three years before diagnosis     

Smoking and dementia in male British doctors: prospective study

ObjectiveTo assess the possible association between smoking and dementia.DesignProspective study.SettingCohort of British male doctors followed up since 1951.Subjects34 439 male British doctors, with 24 133 deaths recorded.ResultsFor all types of dementia combined the relative risk was 0.96 (95% confidence interval 0.78 to 1.18), based on 473 deaths at a mean age of 81 years. For probable or definite Alzheimer''s disease, the relative risk in continuing smokers was 0.99 (0.78 to 1.25), based on 370 deaths at a mean age of 82 years. In aggregate, however, the other prospective studies indicate a direct, although not clearly significant, association between smoking and the onset of dementia in general and of Alzheimer''s disease in particular. ConclusionsContrary to previous suggestions persistent smoking does not substantially reduce the age specific onset rate of Alzheimer''s disease or of dementia in general. If anything, it might increase rather than decrease the rate, but any net effect on severe dementia cannot be large in either direction.     

Relation between nicotine intake and Alzheimer's disease.

OBJECTIVE--To study the association between Alzheimer''s disease and nicotine intake through smoking. DESIGN--Population based case-control study. SETTING--City of Rotterdam and four northern provinces of The Netherlands. SUBJECTS--198 patients with early onset Alzheimer''s disease, 198 controls matched for age and sex, and families of 17 patients in whom Alzheimer''s disease was apparently inherited as an autosomal dominant disorder. MAIN OUTCOME MEASURES--Age of onset of dementia, relative risk of Alzheimer''s disease. RESULTS--89 of 193 patients with Alzheimer''s disease had a history of smoking compared with 102 of 195 controls. Among the patients and controls with a family history of dementia, smoking was significantly less common in those with dementia (40/95 with dementia v 55/96 controls; relative risk 0.35; 95% confidence interval 0.16 to 0.78). The risk of Alzheimer''s disease decreased with increasing daily number of cigarettes smoked before onset of disease (relative risk 0.3 in those smoking greater than 21/day v 1 in non-smokers). In six families in which the disease was apparently inherited as an autosomal dominant disorder, the mean age of onset was 4.17 years later in smoking patients than in non-smoking patients from the same family (p = 0.03). CONCLUSIONS--These findings suggest an inverse association between smoking and Alzheimer''s disease, although smoking cannot be advocated for other health reasons. We speculate that nicotine may have a role in the aetiology of both Alzheimer''s disease and Parkinson''s disease.     

A Clinical Index to Predict Progression from Mild Cognitive Impairment to Dementia Due to Alzheimer's Disease

Background

Mild cognitive impairment is often a precursor to dementia due to Alzheimer''s disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment.

Objective

To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings.

Design and Participants

382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer''s Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study.

Main Predictors Measures

Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales.

Main Outcome Measure

Progression to probable Alzheimer''s disease.

Key Results

Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer''s disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell''s c-statistic was 0.71(95% CI: 0.68–0.75). Fourteen percent of subjects with low risk scores (0–2 points, n = 124) converted to probable Alzheimer''s disease over 3 years, compared to 51% of those with moderate risk scores (3–8 points, n = 223) and 91% of those with high risk scores (9–16 points, n = 35).

Conclusions

An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer''s disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression.     

Neurochemical characteristics of early and late onset types of Alzheimer's disease.

Brains of 49 patients who had died with Alzheimer''s disease and 54 controls were examined. The Alzheimer group exhibited noticeably reduced activity of the cholinergic marker enzyme choline acetyltransferase in the cerebral cortex, but cortical concentrations of noradrenaline, gamma-aminobutyric acid, and somatostatin were also significantly reduced. Analysis of the results according to age at death showed that the older patients, dying in their 9th and 10th decades, had a relatively pure cholinergic deficit confined to temporal lobe and hippocampus, together with a reduced concentration of somatostatin confined to temporal cortex. By contrast, the younger patients, dying in their 7th and 8th decades, had a widespread and severe cholinergic deficit together with the abnormalities of noradrenaline, gamma-aminobutyric acid, and somatostatin, and the younger patients accounted for most of the abnormalities in these systems observed in the overall group. Comparison of the young subjects with Alzheimer''s disease with the older controls did not support the concept of Alzheimer''s disease representing an acceleration of the aging process. These results suggest that Alzheimer''s disease in people aged under 80 may represent a distinct form of presenile dementia which differs in important respects from the dementia of old age.     

Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. Groupe Fran?ais d'Etude de la Tetrahydroaminoacridine.

OBJECTIVE--To see whether combined treatment with oral tacrine (tetrahydroaminoacridine; THA) and lecithin improves the symptoms of patients with Alzheimer''s disease. DESIGN--Multicentre double blind, placebo controlled, random order crossover trial with individual determination of maximum tolerated dosage and four month follow up. SETTING--Outpatient departments at six university neurological centres. PATIENTS--67 Outpatients (24 men, 43 women) aged 53-81 (mean 66 (SD 7.3)) selected according to the following criteria: probable Alzheimer''s disease as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer''s Disease and Related Disorders Association; absence of mood disorder; mini mental state score lower than 26; availability of a close relative able to complete questionnaires; and informed consent of the patient or his or her closest relative, or both. INTERVENTIONS--Mean of 114 mg tacrine or placebo daily plus 1200 mg lecithin daily given in three divided doses for one four week active treatment period and one four week control period without washout at crossover. MAIN OUTCOME MEASURES--Cognitive state as assessed by Folstein''s mini mental state rating scale, behavioural state as assessed by the Stockton geriatric rating scale, and overall state as assessed with a visual analogue scale rated by both the relative and the physician. RESULTS--Compared with placebo tacrine did not improve either the mini mental state score (mean 14.9 (SD 7.3) v 14.8 (7.3)) or the Stockton geriatric score (28.2 (15.7) v 28.7 (17.8)), but a slight and statistically significant improvement occurred in the physician''s score on the visual analogue scale (6.3 (10.2) v 11.6 (17.9)). Seven patients dropped out. Six patients were excluded because of acute hepatitis and one withdrew for personal reasons not related to treatment. Two other patients developed acute hepatitis at the end of the eight week crossover trial and another during the follow up study. Twenty patients complained of gastrointestinal side effects. CONCLUSIONS--Neither short term nor long term treatment with oral tacrine at dosages lower than 125 mg/day improves the symptoms of Alzheimer''s disease. Moreover, these dosages may induce hepatitis (nine of 67 patients in this series).     

阿尔茨海默病和血管性痴呆与血糖代谢水平的关系及危险因素分析

目的:研究阿尔茨海默病和血管性痴呆与血糖代谢水平的关系及危险因素。方法:选取2013年12月到2014年12月我院收治的阿尔茨海默病80例(A组)和血管性痴呆70例(B组),另选取同时期无痴呆者70例(对照组),测量三组入选者血糖各指标水平,并分析阿尔茨海默病和血管性痴呆的危险因素。结果:A组和B组空腹血糖(FPG)均显著高于对照组,胰岛素降解酶(IDE)显著低于对照组,比较差异具有统计学意义(P0.05);B组糖尿病、冠心病和高血压疾病的发病率显著高于A组和对照组,比较差异具有统计学意义(P0.05),A组和B组高血脂发病率均显著高于对照组,比较差异具有统计学意义(P0.05)。结论:阿尔茨海默病和血管性痴呆均与FPD、IDE以及高血脂有较大关系,高血压、冠心病和糖尿病与血管性痴呆有较大关系。     

Low blood pressure and dementia in elderly people: the Kungsholmen project.

OBJECTIVE--To examine the relation between blood pressure and dementia in elderly people. DESIGN--Cross sectional, population based study. SETTING: Kungsholmen district of Stockholm, Sweden. SUBJECTS-- 1642 subjects aged 75-101 years. MAIN OUTCOME MEASURES--Prevalence and adjusted odds ratio of dementia by blood pressure. RESULTS--People with systolic pressure < or = 140 mm Hg were more often diagnosed as demented than those with systolic pressure >140 mm Hg: odds ratios (95% confidence interval) adjusted for age, sex, and education were 2.98 (2.17 to 4.08) for all dementias, 2.91 (1.93 to 4.38) for Alzheimer''s disease, 2.00 (1.09 to 3.65) for vascular dementia, and 5.07 (2.65 to 9.70) for other dementias. Similar results were seen in subjects with diastolic pressure < or = 75 mm Hg compared with those with higher diastolic pressure. When severity and duration of dementia were taken into account, only moderate and severe dementia were found to be significantly related to relatively low blood pressure, and the association was stronger in subjects with longer disease duration. Use of hypotensive drugs and comorbidity with cardiovascular disease did not modify the results for all dementias, Alzheimer''s disease, and other dementias but slightly reduced the association between vascular dementia and diastolic blood pressure. CONCLUSIONS--Both systolic and diastolic blood pressure were inversely related to prevalence of dementia in elderly people. We think that relatively low blood pressure is probably a complication of the dementia process, particularly Alzheimer''s disease, although it is possible that low blood pressure may predispose a subpopulation to developing dementia.     

Las noticias de Madrid (News from Madrid)

Over 5,000 participants attended the 10th International Conference on Alzheimer's Disease (ICAD) and Related Disorders in Madrid, Spain from July 15–20, 2006. Highlights of the conference included reports on brain imaging, the discovery of mutations in the progranulin gene that cause frontotemporal dementia, the finding that neuregulin-1 is a substrate for BACE1 and new interest in the connection between Alzheimer's disease and metabolic syndromes.     

Prevalence of multiple sclerosis in Saskatoon.

In an epidemiologic survey based on a search of all available medical records for 1955 to 1980 at the city''s three general hospitals the prevalence in Saskatoon of probable multiple sclerosis was found to be 111/100,000 and that of combined probable and possible multiple sclerosis 134/100,000 on Jan. 1, 1977. The average annual incidence over the three decades was 4.8/100,000. These prevalence and incidence rates were two to three time greater than those reported for other Canadian cities. Of the 150 individuals with probable multiple sclerosis 87 were living in Saskatoon at the time of onset of the disease; thus, the prevalence of the disease among residents was 64/100,000. The prevalence was 77/100,000 among Saskatchewan-born residents, including those born in Saskatoon, and 48/100,000 among immigrants from other provinces and outside Canada.     

Apolipoprotein E genotype and association between smoking and early onset Alzheimer's disease.

OBJECTIVE--To investigate the hypothesis that differential survival between smokers and non-smokers leading to a decrease in the frequency of the e4 allele of the apolipoprotein E gene may explain the inverse relation between smoking history and early onset Alzheimer''s disease. DESIGN--A population based case-control study. SETTING--The four northern provinces of the Netherlands and metropolitan Rotterdam. SUBJECTS--175 patients with early onset Alzheimer''s disease and two independent control groups of 159 and 457 subjects. MAIN OUTCOME MEASURES--Frequencies of the apolipoprotein e4 allele and relative risk of early onset Alzheimer''s disease. RESULTS--The inverse association between smoking history and early onset Alzheimer''s disease could not be explained by a decrease in the frequency of the apolipoprotein e4 allele. Among carriers of this allele with a family history of dementia subjects with a history of smoking had a strongly reduced risk of early onset Alzheimer''s disease (odds ratio 0.10 (95% confidence interval 0.01 to 0.87)). CONCLUSIONS--The results suggest that the inverse relation between smoking history and early onset Alzheimer''s disease cannot be explained by an increased mortality in carriers of the apolipoprotein e4 allele who smoke. The association is strongly modified by the presence of the apolipoprotein e4 allele as well as by a family history of dementia.     

Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease

The activity of the noradrenergic marker enzyme dopamine-beta-hydroxylase was measured in brains removed postmortem from control patients and patients with Alzheimer''s disease. Enzyme activity was decreased in the frontal and temporal cortices and hippocampus in patients with Alzheimer''s disease, but was within the normal range in patients with depression, multiinfarct dementia, and terminal coma.The decrease in enzyme activity in Alzheimer''s disease may reflect an abnormality of cortical noradrenergic fibres in some patients with the disease.     

Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study.

OBJECTIVE: To determine the association between features of the insulin resistance syndrome and Alzheimer''s disease. DESIGN: Cross sectional population based study. SUBJECTS: 980 people aged 69 to 78 (349 men, 631 women). SETTING: Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES: Presence of features of the insulin resistance syndrome and diagnosis of Alzheimer''s disease by detailed neurological and neuropsychological evaluation. RESULTS: 46 (4.7%) subjects were classified as having probable or possible Alzheimer''s disease. In univariate analyses, apolipoprotein E4 phenotype (odds ratio; 95% confidence interval 3.24: 1.77 to 5.92), age (1.16; 1.05 to 1.29), low level of education (0.82; 0.72 to 0.93), low total cholesterol concentration (0.77; 0.59 to 1.00), high systolic blood pressure (1.01; 1.00 to 1.03), high fasting and 2 hour plasma glucose concentrations (1.11; 1.01 to 1.23 and 1.08; 1.03 to 1.13, respectively), high fasting and 2 hour insulin concentrations (1.05; 1.02 to 1.08 and 1.003; 1.00 to 1.01, respectively), and abnormal glucose tolerance (1.86; 1.23 to 2.80) were significantly associated with Alzheimer''s disease. In multivariate analysis including apolipoprotein E4 phenotype, age, education, systolic blood pressure, total cholesterol concentration, fasting glucose concentration, and insulin concentration, apolipoprotein E4 phenotype, age, education, total cholesterol, and insulin were significantly associated with Alzheimer''s disease. In 532 non-diabetic subjects without the e4 allele hyperinsulinaemia was associated with an increased risk for Alzheimer''s disease (prevalence of disease 7.5% v 1.4% in normoinsulinaemic subjects, P = 0.0004). In contrast, in the 228 with the e4 allele hyperinsulinaemia had no effect on the risk of disease (7.0% v 7.1%, respectively). CONCLUSION: Features of the insulin resistance syndrome are associated with Alzheimer''s disease independently of apolipoprotein E4 phenotype.     

基于BP神经网络和RBF神经网络预测老年痴呆症疾病进展的对比研究

目的:比较反向传播算法(BP)神经网络和径向基函数(RBF)神经网络预测老年痴呆症疾病进展的效果。方法:以老年痴呆症随访数据为研究对象,以性别、年龄、受教育程度、有无高血压、有无高胆固醇、有无心脏病、有无中风史、有无家族史8个指标作为输入变量,以五年随访的MMSE差值为输出变量,构建基于BP神经网络和RBF神经网络的老年痴呆症疾病进展预测模型。结果:与BP神经网络模型相比,RBF神经网络预测的结果更好,能够有效地预测老年痴呆症疾病进展。结论:神经网络模型将老年痴呆症疾病进展预测问题转化为随访数据中相关测量指标与MMSE差值的非线性问题,为复杂的老年痴呆症疾病进展预测提供了新思路。