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There is great interest in developing reliable biomarkers to support antemortem diagnosis of late-onset Alzheimer's disease (AD). Early prediction and diagnosis of AD might be improved by the detection of a proteolytic dysfunction in extracts from cultured AD fibroblasts, producing altered isoelectrophoretic forms of the enzyme transketolase (TK-alkaline bands). The TK profile and apolipoprotein E (APOE) genotype were examined in fibroblasts from 36 clinically diagnosed probable late-onset sporadic AD patients and 38 of their asymptomatic relatives, 29 elderly healthy individuals, 12 neurological non-AD patients, and 5 early-onset AD patients. TK alterations occurred in (i) several probable AD patients regardless of age-of-onset and severity of disease; (ii) all early-onset AD patients and APOE ε 4/4 carriers; and (iii) nearly half of asymptomatic AD relatives. Normal subjects and non-AD patients were all negative. Notably, culture conditions promoting TK alterations were also effective in increasing active BACE1 levels. Overall, the TK assay might represent a low-cost laboratory tool useful for supporting AD differential diagnosis and identifying asymptomatic subjects who are at greater risk of AD and who should enter a follow-up study. Moreover, the cultured fibroblasts were confirmed as a useful in vitro model for further studies on the pathogenetic process of AD.

Intracellular cholesterol metabolism was reported to modulate amyloid-beta (Abeta) generation in Alzheimer's disease (AD). Results presented herein demonstrated that, like brain cells, cultured skin fibroblasts from AD patients contained more cholesterol esters than fibroblasts from healthy subjects. Particularly, Oil Red-O, Nile Red, and filipin staining highlighted higher levels of neutral lipids which responded to inhibitors of acyl-coenzyme A:cholesterol acyl-transferase (ACAT-1), associated with an increase in free cholesterol. ACAT-1 mRNA levels increased significantly in AD fibroblasts, whereas those of sterol regulatory element binding protein-2, neutral cholesterol ester hydrolase, and ATP-binding cassette transporter member 1 were markedly down-regulated. Instead, mRNA levels of low-density lipoprotein receptor, hydroxy-methyl-glutaryl-coenzyme A reductase, caveolin-1, and amyloid-beta protein precursor (AbetaPP) were virtually unchanged. Notably, mRNA levels of both beta-site AbetaPP-cleaving enzyme 1 (BACE1) and neprilysin were significantly down-regulated. An increase in Abeta(40) and Abeta(42) immunostaining and a decrease in BACE1 active form were also found in AD versus control fibroblasts. Altogether, these findings support the hypothesis that the derangement of cholesterol homeostasis is a systemic alteration involving central but also peripheral cells of AD patients, and point to cholesterol ester levels in AD fibroblasts as an additional metabolic hallmark useful in the laboratory and clinical practice.

Alzheimer's disease (AD) is a progressive neurodegenerative illness and the most frequent cause of dementia in the elderly. The identification of activated microglia within neuritic plaques, coupled with the presence of numerous inflammatory proteins, suggests that inflammation is an integral part of the pathogenetic process in AD. In the present paper we have investigated the levels of circulating inflammatory mediators as potential AD biomarkers concentrating essentially on (a) soluble CD40 (sCD40), a member of the tumor necrosis factor receptor superfamily lacking the membrane-associated endodomain by alternative splicing, and (b) transforming growth factor (TGF)-beta 1, a cytokine deeply involved in AD and playing a protective role on CNS. Decrease of TGF-beta1 in AD patients could enhance the effects of pro-inflammatory cytokines produced by activated microglia as well as the expression of factors, such as the CD40/CD40 ligand complex, by microglia and astrocytes. Total venous blood samples were obtained from 33 patients with clinical diagnosis of possible late-onset AD, 40 healthy age-matched and 11 healthy young individuals. A significant increase of sCD40 levels plasma of AD patients versus healthy controls was measured, concomitantly with a decrease in TGF-beta1 concentration. These variations, however, showed no correlation with the expression of ApoE epsilon 4 allele, which was determined in order to assess the different frequency of this risk factor between AD and control groups. Since no comparable modifications were detected in patients affected by Parkinson's disease or non-AD-based dementia, we propose that sCD40 and TGF-beta1 plasma levels might represent possible differential biomarkers of AD, and be useful pre-mortem to support the clinical diagnosis of late-onset AD.

Comprehensive geriatric assessment has become synonymous with geriatric practice. This includes evaluation of the older person's physical and mental health, and the functional and social status. We propose a new way of representing a person's condition, called the "polar diagram". This shows the subject's scores on the evaluation scales that are arranged in radial positions inside a circle. The outer part of the circle corresponds to the best condition. Gaps between the best condition and the actual scores are easily identified. The diagram can be employed to monitor the subject's condition and to assess any changes in outcomes.

The aim of this study was to evaluate factors predicting length of stay in hospital of geriatric patients. Study participants were 402 patients (183 males and 219 females) consecutively admitted to four geriatric wards located in Chieti, Perugia, Pescara and Prato, Italy. Information on potential predictors of length of stay was collected; in particular, we assessed the presence and severity of specific chronic medical conditions, level of physical function, cognitive status, and depressive symptoms. Moreover, information on family and social support was obtained. In general, participants were old, often cognitively impaired and physically disabled. Average length of stay ranged from 9.4 +/- 3.3 days (Perugia) to 14.1 +/- 7.2 days (Chieti), and was statistically different across centers (p < 0.001). None of the specific medical diagnoses was associated with different length of stay. However, higher comorbidity score (p < 0.001), living alone (p < 0.01), lower MMSE score (p = 0.03), and poor functional status (p = 0.05) were all associated with longer length of stay. When these variables were included in a multivariate model predicting length of stay, differences between centers were no longer statistically significant. Findings of this study show that specific medical diagnoses are not adequate instruments to estimate length of stay in geriatric units. Other assessment systems based on extension of the social network, comorbidity, and the cognitive as well as the functional level need to be developed.

The aim of the study was to evaluate which characteristics of geriatric patients account for readmission to hospital, 6 months after discharge. All patients (203 females, 176 males) consecutively admitted over a two-month period to four acute geriatric care units, located in the cities of Chieti, Perugia, Pescara and Prato, participated in the study. Data that could potentially explain early and late readmissions were collected for each patient. Prevalence of diseases and comorbidity were assessed with the Cumulative Illness Rating Scale (CIRS); physical function by self-report (ADL, IADL) and objective (Stand and Walking Speed) measures; cognitive level by MMSE; and depressive symptoms by the Geriatric Depression Scale (GDS). Information on family and social support were also obtained. After discharge, data on hospital readmissions were collected for six months. For each readmitted patient (cases), medical records were reviewed, and supplementary information was obtained from families and general practitioners. Readmissions were classified as "early" (within the first three months), "late" (within the third and sixth month), and "multiple" (2 or more readmissions irrespective of the period). Patients not readmitted (alive at home) were considered as controls. Systematic differences between centers and between periods of readmissions were evaluated using one-way analyses of variance, and Pearson's chi 2 test. Factors related to early, late, and multiple readmission were identified in multivariate logistic regression models. On univariate analysis, patients readmitted over the first three-month period were sicker than controls (CIRS classes 3-4: 52.1% vs 34.1%), had more social problems or behavioral symptoms, and were more functionally impaired (ADL dependencies 3.3 +/- 0.4 vs 2.1 +/- 0.2). Patients who were readmitted between the third and the sixth month after discharge had a significantly higher CIRS total score (p = 0.006). Patients with multiple readmissions had more severe diseases, and more social problems. On multivariate analysis, early readmission was associated with unsatisfactory social conditions, living alone, severity of diseases and cognitive impairment, while late readmission was associated with comorbidity only. Multiple readmissions were related only to social factors, and to hospital admission before the baseline evaluation. The findings of this study suggest that interventions aimed at improving unfavorable social conditions may reduce the rate of rehospitalization in geriatric patients.

The objective of this retrospective, case-series study was to examine the relationship between disability in Instrumental Activities of Daily Living (IADLs) and cognitive impairment measured by the Mini-Mental State Examination (MMSE), and how this relationship was influenced by different levels of formal education. The setting of the study was the Cognitive Disorders Center of the Local Sanitary Unit (USL) No. 4 in Prato (Italy). Independence in IADL was strongly related to MMSE scores. A score of less than 24 at the MMSE was predictive of disability in at least one IADL with 0.82 sensitivity and 0.73 specificity. However, when only people with a very low level of formal education were considered, the best threshold predicting IADL disability was 17 (sensitivity 0.76, specificity 0.75). Thus, scholastic achievement is an effect modifier of the relationship between cognitive status, as measured by the MMSE, and IADL disability. Subjects with low education level and poor performance at the MMSE are often independent in activities making demand on cognitive function, such as IADLs. These results suggest that a lower MMSE cut-off score should be considered when screening for cognitive impairment in these persons.

The urinary excretion of single or multiple oral doses of amantadine hydrochloride by three elderly patients has been studied by gas chromatography. Steady state amounts in urine were about 230-240 mg per day. The half life of urinary excretion was approximately 34.17 hours. Urine collection from aged subjects is difficult.

In a controlled clinical trial, amantadine 400 mg daily, 200 mg daily and 200 mg daily given with 20 mg of pemoline daily were compared with placebo in the treatment of elderly patients suffering from involutional cerebropathy characterized by psychomotor slowing down. The results showed that amantadine 400 mg daily was superior to placebo but was associated with a high incidence of side-effects (37 per cent), amantadine 200 mg daily was not superior to placebo but when pemolint 20 mg daily was added the combination was superior to placebo and few side-effects were reported.