The Mini Mental State Examination at the Time of Alzheimer's Disease and Related Disorders Diagnosis,According to Age,Education, Gender and Place of Residence: A Cross-Sectional Study among the French National Alzheimer Database

The aim of this study

was firstly to describe the MMSE (Mini-Mental State Examination) score upon initial diagnosis of Alzheimer''s disease and related disorders among the French population, according to age. Secondly, education, gender and place of residence were studied as factors potentially associated with delayed Alzheimer''s disease diagnosis.

Design

we conducted a cross sectional analysis of the French National Alzheimer database (BNA). Data from 2008 to 2012 were extracted. Patients were selected at the moment of their first diagnosis of AD (n = 39,451).

Results

The MMSE score at initial diagnosis dropped significantly with increasing age. The test score increased with the degree of educational background regardless of age. Gender and place of residence were significantly related to the MMSE score, women and persons living in medical institutions having lower MMSE scores under the age of 90 years and at all educational levels.

Conclusions

Health care professionals should be aware of these risk factors in order to maximize chances of earliest possible diagnosis of Alzheimer''s disease and related disorders.     

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.     

重酒石酸卡巴拉汀与盐酸多奈哌齐对阿尔兹海默症患者认知功能及血清 缓激肽水平的影响

目的:探讨重酒石酸卡巴拉汀联合盐酸多奈哌齐对阿尔兹海默症患者认知功能及血清缓激肽水平的影响。方法:收集我院就诊或住院治疗的96例阿尔兹海默症患者,随机分为实验组和对照组,每组48例。对照组患者给予盐酸多奈哌齐片治疗,实验组患者在对照组基础上给予重酒石酸卡巴拉汀胶囊治疗。观察并比较两组患者治疗前后简易智能状态量表(MMSE)评分、痴呆量表(Blessed-Roth)评分、阿尔兹海默症评定量表(ADAS-Cog)评分以及血清缓激肽(BK)水平的变化情况。结果:与治疗前相比,两组患者治疗后MMSE评分升高(P0.05),Blessed-Roth评分以及ADAS-Cog评分下降(P0.05),血清BK水平下降(P0.05);与对照组相比,实验组患者的MMSE评分较高(P0.05),Blessed-Roth评分,ADAS-Cog评分以及血清BK水平较低(P0.05);结论:重酒石酸卡巴拉汀联合盐酸多奈哌齐能够更有效改善阿尔兹海默症患者的认知功能,可与其降低血清BK水平有关。     

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。     

阿尔茨海默病患者血清IL-10、IL-17、IL-33与肠道菌群相对丰度和认知功能的相关性分析

摘要 目的：分析阿尔茨海默病（AD）患者血清白介素（IL）-10、IL-17、IL-33与肠道菌群相对丰度和认知功能的相关性。方法：选择上海交通大学医学院附属第九人民医院老年科以及黄浦分院神经内科于2020年4月~2023年4月期间收治的AD患者 98例作为研究对象。根据临床痴呆评定量表（CDR）将AD患者分为轻度组（n=36）、中度组（n=39）、重度组（n=23）。对比三组患者的IL-10、IL-17、IL-33、肠道菌群相对丰度、认知功能评分。采用Pearson相关性分析AD患者血清IL-10、IL-17、IL-33与肠道菌群相对丰度和认知功能的相关性。结果：重度组、中度组的IL-17水平高于轻度组,且重度组高于中度组（P<0.05）。重度组、中度组IL-10、IL-33水平低于轻度组,且重度组低于中度组（P<0.05）。重度组、中度组的梭菌纲、厚壁菌门、梭菌科、梭菌目低于轻度组,且重度组低于中度组（P<0.05）。重度组、中度组的拟杆菌门、拟杆菌纲、拟杆菌目、产碱杆菌科高于轻度组,且重度组高于中度组（P<0.05）。重度组、中度组简易精神状态量表（MMSE）评分低于轻度组,且重度组低于中度组（P<0.05）。Pearson相关性分析结果显示,IL-10、IL-33与MMSE评分、厚壁菌门、梭菌纲、梭菌目、梭菌科呈正相关,与拟杆菌门、拟杆菌纲、拟杆菌目、产碱杆菌科呈负相关（P<0.05）。IL-17与MMSE评分、厚壁菌门、梭菌纲、梭菌目、梭菌科呈负相关,与拟杆菌门、拟杆菌纲、拟杆菌目、产碱杆菌科呈正相关（P<0.05）。结论：AD患者认知功能下降,血清IL-10、IL-17、IL-33水平异常变化,患者体内肠道菌群相对丰度异常,且IL-10、IL-17、IL-33水平与肠道菌群相对丰度、认知功能存在一定的相关性。     

Economic Impact of Dementia by Disease Severity: Exploring the Relationship between Stage of Dementia and Cost of Care in Taiwan

Objective

Given the shortage of cost-of-illness studies in dementia outside of the Western population, the current study estimated the annual cost of dementia in Taiwan and assessed whether different categories of care costs vary by severity using multiple disease-severity measures.

Methods

This study included 231 dementia patient–caregiver dyads in a dementia clinic at a national university hospital in southern Taiwan. Three disease measures including cognitive, functional, and behavioral disturbances were obtained from patients based on medical history. A societal perspective was used to estimate the total costs of dementia according to three cost sub-categories. The association between dementia severity and cost of care was examined through bivariate and multivariate analyses.

Results

Total costs of care for moderate dementia patient were 1.4 times the costs for mild dementia and doubled from mild to severe dementia among our community-dwelling dementia sample. Multivariate analysis indicated that functional declines had a greater impact on all cost outcomes as compared to behavioral disturbance, which showed no impact on any costs. Informal care costs accounted for the greatest share in total cost of care for both mild (42%) and severe (43%) dementia patients.

Conclusions

Since the total costs of dementia increased with severity, providing care to delay disease progression, with a focus on maintaining patient physical function, may reduce the overall cost of dementia. The greater contribution of informal care to total costs as opposed to social care also suggests a need for more publicly-funded long-term care services to assist family caregivers of dementia patients in Taiwan.     

Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group

ObjectiveTo evaluate the efficacy and safety of galantamine in the treatment of Alzheimer''s disease.DesignRandomised, double blind, parallel group, placebo controlled trial.Setting86 outpatient clinics in Europe and Canada.Participants653 patients with mild to moderate Alzheimer''s disease.InterventionPatients randomly assigned to galantamine had their daily dose escalated over three to four weeks to maintenance doses of 24 or 32 mg.ResultsAt six months, patients who received galantamine had a significantly better outcome on the 11 item cognitive subscale of the Alzheimer''s disease assessment scale than patients in the placebo group (mean treatment effect 2.9 points for lower dose and 3.1 for higher dose, intention to treat analysis, P<0.001 for both doses). Galantamine was more effective than placebo on the clinician''s interview based impression of change plus caregiver input (P<0.05 for both doses v placebo). At six months, patients in the higher dose galantamine group had significantly better scores on the disability assessment for dementia scale than patients in the placebo group (mean treatment effect 3.4 points, P<0.05). Apolipoprotein E genotype had no effect on the efficacy of galantamine. 80% (525) of patients completed the study.ConclusionGalantamine is effective and well tolerated in Alzheimer''s disease. As galantamine slowed the decline of functional ability as well as cognition, its effects are likely to be clinically relevant.     

Effects of Gingko biloba supplementation in Alzheimer's disease patients receiving cholinesterase inhibitors: Data from the ICTUS study

Ginkgo biloba (Gb) is currently the most investigated and adopted herbal remedy for cognitive disorders and Alzheimer's disease (AD). Nevertheless, its efficacy in the prevention and treatment of dementia still remains controversial. Specifically, the added effects of Gb in subjects already receiving “conventional” anti-dementia treatments have been to date very scarcely investigated. We evaluated whether the use of Gb is associated with additional cognitive and functional benefit in AD patients already in treatment with cholinesterase inhibitors (ChEIs).Data are from mild to moderate AD patients under ChEI treatment recruited in the Impact of Cholinergic Treatment USe (ICTUS) study. Mixed model analyses were performed to measure six-monthly modifications in the Mini Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score, and the Activities of Daily Living (ADL) scale over a follow-up of 1 year according to the additional Gb supplementation.A total of 828 subjects were considered for the present analyses. Significantly different modifications at the MMSE score over the 12-month follow-up were reported between patients on combined therapy compared to those only taking ChEIs. On the contrary, the modification of the ADAS-Cog score between the two groups did not show statistically significant differences, although similar trends were noticed. No significant modifications of the two adopted outcome measures were observed at the mid-term 6-month evaluation. The modifications over time of the ADL score did not show statistically significant differences between the two groups of interest.Our findings suggest that Gb may provide some added cognitive benefits in AD patients already under ChEIs treatment. The clinical meaningfulness of such effects remains to be confirmed and clarified.     

血清NGF、BDNF、GFAP水平与老年血管性痴呆严重程度的相关性分析

目的:探讨血清神经生长因子(Nerve Growth Factor,NGF)、脑源性神经营养因子(Brain Derived Neural Nutrition Factor, BDNF)、胶质纤维酸性蛋白(Glial Fibrillary Acidic Protein,GFAP)水平与老年血管性痴呆严重程度的相关性。方法:选择我院2016年1月至2018年12月收治的81例老年血管性痴呆患者,根据简易精神状态检查表(MMES)评分将其分为三组,以MMSE评分21～26分者为轻度组(26例),10～20分者为中度组(28例),0～9分者为重度组(27例),同时选择来院体检的50例健康者作为对照组,检测和比较各组的血清NGF、BDNF、GFAP水平,分析血清NGF、BDNF、GFAP水平与老年血管性痴呆患者MMSE分值的相关性。结果:老年血管性痴呆者的血清NGF、GFAP水平明显高于对照组(P0.05),血清BDNF水平明显低于对照组(P0.05)。轻度组、中度组、重度组的血清NGF、GFAP、BDNF水平对比差异均有统计学意义(P0.05):NGF水平:轻度组中度组重度组,BDNF水平:轻度组中度组重度组;GFAP水平:轻度组中度组重度组。血清NGF、BDNF水平与MMSE分值评分呈显著正相关(r_1=0.652,r_2=0.671,P0.05),血清GFAP水平与MMSE分值呈显著负相关(r3=-0.681,P0.05)。结论:血清NGF、BDNF、GFAP水平均与老年血管性痴呆的严重程度密切相关,可能用于评估老年血管性痴呆病情的严重程度。     

Gray and White Matter Changes in Subjective Cognitive Impairment,Amnestic Mild Cognitive Impairment and Alzheimer's Disease: A Voxel-Based Analysis Study

Subjective cognitive impairment may be a very early at-risk period of the continuum of dementia. However, it is difficult to discriminate at-risk states from normal aging. Thus, detection of the early pathological changes in the subjective cognitive impairment period is needed. To elucidate these changes, we employed diffusion tensor imaging and volumetry analysis, and compared subjective cognitive impairment with normal, mild cognitive impairment and Alzheimer''s disease. The subjects in this study were 39 Alzheimer''s disease, 43 mild cognitive impairment, 28 subjective cognitive impairment and 41 normal controls. There were no statistically significant differences between the normal control and subjective cognitive impairment groups in all measures. Alzheimer''s disease and mild cognitive impairment had the same extent of brain atrophy and diffusion changes. These results are consistent with the hypothetical model of the dynamic biomarkers of Alzheimer''s disease.     

Community occupational therapy for older patients with dementia and their care givers: cost effectiveness study

Objective To assess the cost effectiveness of community based occupational therapy compared with usual care in older patients with dementia and their care givers from a societal viewpoint.Design Cost effectiveness study alongside a single blind randomised controlled trial.Setting Memory clinic, day clinic of a geriatrics department, and participants’ homes.Patients 135 patients aged ≥65 with mild to moderate dementia living in the community and their primary care givers.Intervention 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision.Main outcome measures Incremental cost effectiveness ratio expressed as the difference in mean total care costs per successful treatment (that is, a combined patient and care giver outcome measure of clinically relevant improvement on process, performance, and competence scales) at three months after randomisation. Bootstrap methods used to determine confidence intervals for these measures.Results The intervention cost €1183 (£848, $1738) (95% confidence interval €1128 (£808, $1657) to €1239 (£888, $1820)) per patient and primary care giver unit at three months. Visits to general practitioners and hospital doctors cost the same in both groups but total mean costs were €1748 (£1279, $2621) lower in the intervention group, with the main cost savings in informal care. There was a significant difference in proportions of successful treatments of 36% at three months. The number needed to treat for successful treatment at three months was 2.8 (2.7 to 2.9).Conclusions Community occupational therapy intervention for patients with dementia and their care givers is successful and cost effective, especially in terms of informal care giving.     

Development of a Screening Algorithm for Alzheimer's Disease Using Categorical Verbal Fluency

We developed a weighted composite score of the categorical verbal fluency test (CVFT) that can more easily and widely screen Alzheimer''s disease (AD) than the mini-mental status examination (MMSE). We administered the CVFT using animal category and MMSE to 423 community-dwelling mild probable AD patients and their age- and gender-matched cognitively normal controls. To enhance the diagnostic accuracy for AD of the CVFT, we obtained a weighted composite score from subindex scores of the CVFT using a logistic regression model: logit (case)  = 1.160+0.474× gender +0.003× age +0.226× education level – 0.089× first-half score – 0.516× switching score -0.303× clustering score +0.534× perseveration score. The area under the receiver operating curve (AUC) for AD of this composite score AD was 0.903 (95% CI = 0.883 – 0.923), and was larger than that of the age-, gender- and education-adjusted total score of the CVFT (p<0.001). In 100 bootstrapped re-samples, the composite score consistently showed better diagnostic accuracy, sensitivity and specificity for AD than the total score. Although AUC for AD of the CVFT composite score was slightly smaller than that of the MMSE (0.930, p = 0.006), the CVFT composite score may be a good alternative to the MMSE for screening AD since it is much briefer, cheaper, and more easily applicable over phone or internet than the MMSE.     

Epidemiology of Alzheimer's presenile dementia in Scotland, 1974-88.

OBJECTIVE--To describe the epidemiology of presenile Alzheimer''s disease in Scotland from 1974 to 1988. DESIGN--Retrospective review of hospital records of patients aged less than 73 years admitted to psychiatric hospital with various diagnoses of dementia. Diagnoses were classified by National Institute for Communicative Disorders and Stroke and Alzheimer''s Disease and Related Disorders Association Criteria and the Hachinski score. Completeness of the study sample was evaluated by scrutiny of neurology outpatient and general hospital records. SETTING--All general psychiatric hospitals in Scotland. SUBJECTS--All patients with onset of dementia aged 40-64. MAIN OUTCOME MEASURES--Probable and broad Alzheimer''s disease, sex of patient, age at onset. RESULTS--5874 psychiatric hospital records, 129 neurology outpatient records, and 89 records from non-psychiatric hospitals were examined. 317 patients met criteria for probable Alzheimer''s disease, 569 met criteria for broad Alzheimer''s disease, and 267 met those for multi-infarct dementia. Minimal incidences per 100,000 population aged 40-64 years were 22.6 (95% confidence interval, 20.2 to 25.2) and 40.5 (38.9 to 42.3) per 100,000 for probable and broad Alzheimer''s disease. In the 1981 census year the annual incidence of probable Alzheimer''s disease was 1.6 (1.0 to 2.6). Women were at greater risk with incidence rates for probable Alzheimer''s disease of 28.2 (24.5 to 32.4) per 100,000 compared with 16.5 (13.8 to 19.8) per 100,000 for men. The incidence per 100,000 for multi-infarct dementia was greater in men (25.1, 23.3 to 27.1) than women (13.4, 12.1 to 14.8). CONCLUSION--Female sex seems to be positively associated with development of Alzheimer''s disease before age 65 years.     

华生关怀理论对老年痴呆症患者的临床干预效果

目的:探索华生关怀理论在老年痴呆症患者临床护理中的应用效果,为临床护理提供参考。方法:选择2012年3月至2014年3月我院收治的老年痴呆患者200例,随机分为治疗组和对照组。对照组采用常规护理措施,治疗组采用华生关怀理论进行干预。分别于干预前后采用简易智能量表(MMSE)、蒙特利尔认知评估量表(MOCA)、AD评定量表认知部分(ADAS-Cog)、日常生活活动量表(ADL)、中医症状积分量表对两组患者进行测评。结果:与干预前比较,两组患者干预后的MMSE和MOCA评分显著升高,ADAS-Cog、ADL和中医症状积分明显降低,差异具有统计学意义(P0.05);与对照组比较,治疗组患者变化更明显(P0.01)。两组患者干预前后的血尿常规、肝肾功能及心电图等指标无显著差异(P0.05)。结论:利用华生关怀理论护理老年痴呆症患者,不仅能改善患者的病情,缓解心理压力,而且有利于减轻家庭和社会负担。     

Deficient Liver Biosynthesis of Docosahexaenoic Acid Correlates with Cognitive Impairment in Alzheimer's Disease

Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer''s disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer''s disease, compared to control subjects (P = 0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P = 0.005) and mid-frontal cortex (P = 0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer''s disease patients than control subjects (P = 0.011). Liver docosahexaenoic/α-linolenic ratios correlated positively with MMSE scores (r = 0.78; P<0.0001), and negatively with global deterioration scale grades (P = 0.013). Docosahexaenoic acid precursors, including tetracosahexaenoic acid (C24:6n-3), were elevated in liver of Alzheimer''s disease patients (P = 0.041), whereas expression of peroxisomal d-bifunctional protein, which catalyzes the conversion of tetracosahexaenoic acid into docosahexaenoic acid, was reduced (P = 0.048). Other genes involved in docosahexaenoic acid metabolism were not affected. The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer''s disease patients, lessening the flux of this neuroprotective fatty acid to the brain.     

Short term response is predictive of long term response to acetylcholinesterase inhibitors in Alzheimer’s disease: A starting point to explore Bayesian approximation in clinical practice

This study was aimed at identifying, in 203 patients with Alzheimer''s disease followed during long-term treatment with Acetylcholinesterase inhibitors (ChEIs), the predictive factors of the clinical response among cognition (MMSE), functioning (BADL and IADL) measures and age and gender at the baseline (T0). The ANCOVA test showed a significant association between MMSE scores at time T0 and T3, and the variation T9 to T0, T15 to T0 and T21 to T0 of the MMSE scores, using also gender, age and drug as covariates. The significance was higher for the patients affected by mild dementia. Regarding functional activities, a significant relationship was detected, by the ANCOVA test, only between the scores at T3 and the variation T15 to T0 for BADL, and the variation T9 to T0, T15 to T0 for IADL, respectively. Our results confirm, in a real world setting, that ChEIs provide long-term cognitive benefit, which is correlated to, and predictable by, the short-term response (within the third month) as well as the cognitive status (evaluated by means of the MMSE) at the beginning of the treatment. These factors should be the basis of any cost/effectiveness algorithm in health economic decision models.     

Effect of tetrahydroaminoacridine on cognition,function and behaviour in Alzheimer's disease.

OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer''s disease. DESIGN: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration. SETTING: Referral-based geriatric practice in a community hospital. PATIENTS: Thirty-four patients with moderate to severe Alzheimer''s disease. Subjects were included if they had stage 3 to 6 disease (as determined by the Reisberg scale) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin. INTERVENTIONS: Fifty to 100 mg of THA daily and matched placebo. RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study; however, all 22 who completed the study were able to tolerate at least the minimum dose. For the 22 patients there was no clinically or statistically significant effect of THA on cognition, functional status or behaviour. The results for individual patients showed no subgroup of THA-responsive patients. CONCLUSION: THA has no clinically important benefits in Alzheimer''s disease and is associated with appreciable toxic effects.     

Serial visual evoked potential recordings in Alzheimer's disease.

Primary presenile dementia slows the major positive component of the visual evoked potential to flash stimulation but does not affect the visual evoked potential to patterned stimulation. The progressive effect of Alzheimer''s disease was followed in a 58 year old woman over three and a half years from the development of the earliest symptoms to complete mental incapacity. The pattern reversal visual evoked potential remained normal, but the flash visual evoked potential gradually slowed from 129 ms in 1981 to 153 ms in 1984. The severity of the abnormality of the flash visual evoked potential thus reflected the severity of the dementia. Electroencephalography, computed tomography, and psychometric tests indicated generalised cortical disease, but the results were not specific to dementia. The combination of a slowed flash and normal pattern visual evoked potential seems to be specific to Alzheimer''s disease and supports the use of flash and pattern visual evoked potentials in routine diagnostic testing for this condition.     

Positron emission tomography in patients with clinically diagnosed Alzheimer's disease.

Fourteen patients who had clinically diagnosed Alzheimer''s disease with mild to severe dementia (mean age 69.1 years) were evaluated by calculation of local cerebral metabolic rate for glucose (LCMR-gl) based on uptake of 18F-2-fluoro-2-deoxyglucose (FDG) detected with positron emission tomography (PET). PET scanning showed that the patients had significantly lower LCMR-gl values than 11 age-matched neurologically normal volunteers (mean age 66.3 years). The differences were most marked in the temporal cortex, followed by the frontal, parietal and occipital cortex. In each case the LCMR-gl value was below the lowest control value in at least one cortical area and usually in several; the reduction in LCMR-gl and the number of regions involved in the patients increased with the severity of the dementia. Deficits noted in neuropsychologic testing generally correlated with those predicted from loss of regional cortical metabolism. The patients with Alzheimer''s disease were also examined with magnetic resonance imaging, computed tomography or both; the degree of atrophy found showed only a poor correlation with the neuropsychologic deficit. Significant atrophy was also noted in some of the controls. A detailed analysis of LCMR-gl values in selected cerebral regions of various sizes refuted the hypothesis that the reduction in cortical glucose metabolism in Alzheimer''s disease is due to the filling by metabolically inert cerebrospinal fluid of space created by tissue atrophy.     

Efficacy of tacrine and lecithin in mild to moderate Alzheimer's disease: double blind trial.

OBJECTIVE--To assess the efficacy of tacrine and lecithin in treating Alzheimer''s disease over nine months. DESIGN--Double blind randomised controlled trial. SETTING--Outpatients clinic of university department of geriatric medicine. SUBJECTS--53 subjects (26 women, 27 men) with probable Alzheimer''s disease. 41 completed the dose finding phase and were randomised to treatment. 32 (14 tacrine, 18 placebo) completed nine months'' treatment. INTERVENTIONS--Lecithin and tacrine or lecithin and placebo for 36 weeks. MAIN OUTCOME MEASURES--Scores on neuropsychological tests sensitive to deficits in the cholinergic system; mini-mental state score; behaviour change; mood; functional state; and stress in carers. RESULTS--The tacrine and placebo groups were similar except that the tacrine group had a longer duration of disease (mean 5.4 v 2.5 years in placebo group; P = 0.003). Only 17 of the 32 patients could tolerate the maximum dose of tacrine (100 mg). No significant difference was found between the groups for any of the tests after nine months'' treatment except for the digit backwards test, which is insensitive to cholinergic deficit. Analysis of subjects taking the maximum dose of tacrine and of subjects with mild dementia also found no differences. CONCLUSIONS--Tacrine produces no clinically relevant improvement over 36 weeks at the doses tolerated by these patients.