Acid-stable serine proteinase inhibitors in the urine of Alzheimer disease subjects.

A comparative study of the levels of acid-stable proteinase inhibitors (kallikrein and trypsin inhibitors) in the urine of healthy and Alzheimer subjects, of both sexes, has been performed. A preliminary characterization of the purified inhibitors indicates that the urinary antitryptic activity is accounted for by the presence of the well known Urinary Trypsin Inhibitor (UTI) while an apparently new molecule appears to be responsible for the antikallikrein activity. The urinary levels of kallikrein inhibitors are very similar in healthy and sick subjects while the levels of trypsin inhibitors appear significatively increased in Alzheimer subjects of both sexes. The data presented here support the hypothesis that unpaired proteolytic processes could be involved in the pathogenesis of Alzheimer's disease and suggest that the levels of urinary acid-stable inhibitors may prove to be useful markers of the disease.

Survival and dementia: a 7-year follow-up of an Italian elderly population.

The objective of this study was to investigate the association between dementia and mortality in an elderly Italian population. Demented subjects were identified by a previous prevalence study of Alzheimer's disease (AD) and specific dementing disorders. The study sample included all inhabitants of Appignano aged 60 and over (778 subjects), and was followed-up over a period of about 7 years. Periodic records of dates of death were obtained from the Registry Office of Appignano. We found considerably higher mortality ratios for subjects previously diagnosed as having dementia syndrome (12.5% at 1 year and 81.3% at about 7 years) than for those who were non-demented (3.0% at 1 year and 21.5% at about 7 years). In the group of demented subjects (N = 48), we also investigated the influence of sex, age, and specific dementing disorders on mortality ratios. The percentage of demented subjects who died during the whole period of follow-up was higher among men than women (100% vs. 66.7%) and increased considerably with increasing age (50.0% for age class 60-69, 76.5% for age class 70-79, and 86.2% for age class 80+). Mortality of subjects with multi-infarct dementia (MID) and mixed dementia (MD) tended to be slightly higher than in subjects affected by AD. Our results are consistent with those reported in previous population-based studies on survival of dementia patients.

Study on the validity of the Hodkinson Abbreviated Mental Test Score (AMTS) in detecting dementia of elderly subjects in appignano (Macerata province), Italy.

The accuracy of the Hodkinson Abbreviated Mental Test Score (AMTS) as a screening instrument for dementia has been investigated in an Italian population. The AMTS was administered by nonmedical personnel to a random sample of 109 subjects over the age of 59; each subject was evaluated by a standardized dementia protocol (DSM-III criteria); and scores on the AMTS were compared to corresponding clinical diagnoses (standard for comparison). Five of the 109 subjects were found to be affected by dementia upon clinical investigation. Although a score of 6 showed the best combination of sensitivity (80%) and specificity (89%), only a score of 7 yielded 100% sensitivity (71% specificity). At all screening levels, specificity was higher for males vs. females, for younger vs. older, and for more educated vs. less educated subjects. The results suggest that brief cognitive tests may be successfully used in population screening for dementia, and that tests not requiring reading, writing or drawing, and not strictly dependent on the education level, are preferable; however, the instruments should be adapted and validated in the target population.

Posatirelin for the treatment of degenerative and vascular dementia: results of explanatory and pragmatic efficacy analyses.

In order to confirm the efficacy and safety of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having cholinergic, catecholaminergic and neurotrophic activities, a multicentre, double-blind, controlled study versus placebo was planned in elderly patients suffering from Alzheimer's disease and vascular dementia, according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria, respectively. The trial consisted of a 2-week run-in phase with placebo administered once a day orally, followed by a double-blind period of 3 months, with posatirelin or placebo administered once a day intramuscularly. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale (primary variable) and the Rey Memory Test (secondary variable). Laboratory tests, vital signs and adverse events were monitored. A total of 360 patients were randomized, the intent-to-treat sample (ITT) being made up of 357 patients and the per protocol sample (PP) of 260 patients. Both pragmatic and explanatory analyses showed significant differences between treatment groups in the GBS Rating Scale and the Rey Memory Test, with no difference in the two types of dementia. No difference between treatments was observed in safety variables, the incidence of adverse events in the posatirelin group being 7.3%. The study confirms previous results showing that treatment with posatirelin can improve cognitive and functional abilities of patients suffering from degenerative or vascular dementia.

[Clinical investigation on depression on a randomized and stratified sample in an elderly population]. / Indagine clinica sulla depressione in un campione randomizzato e stratificato di popolazione anziana.

The prevalence of depression in the elderly was investigated in a random stratified sample of 100 subjects from the general population of Appignano (Macerata, Regione Marche, Italy). After sampling with the simple random method, each subject underwent a diagnostic work-up including: a) three psychodiagnostic tests (Short Scale for the Assessment of Mental Health--SSAMH, Geriatric Depression Scale--GDS, and Scale for the Self-evaluation of Depression from the Psychogeriatric Interview--PGI) and b) psychiatric evaluation (according to DSM-III-R diagnostic criteria). Results were as follows: a) all the 3 tests (SSAMH, GDS, PGI) were suitable for the goals of this research, with a sensibility of 95.4%, 90.9%, and 95.4%, and a specificity of 90.4%, 88.9%, and 90.5%, respectively; b) the prevalence of depression in the sample was 25.9% (26.1% in females and 25.6% in males); c) the most common disorder was dysthymia, with higher percentage in females than in males (75% and 50% of all the depressive syndromes, respectively); d) the prevalence of depression was higher in females 60-69 years old and in males 70-79 years old.

Education and occupation as risk factors for dementia: a population-based case-control study.

To further investigate the putative associations between education and dementia and between occupation and dementia, we conducted a population-based case-control study. Cases were all subjects affected by dementia ascertained through a prevalence survey conducted in the municipality of Appignano, Macerata Province, Italy. For each case (n = 48), we randomly selected 2 population controls residing in the same municipality and matched for age and sex (n = 96). Information regarding exposures was collected by nonmedical personnel during the first contact for the prevalence survey. Although we found a striking trend toward decreasing prevalence with increasing education, this association was suggestive but not significant after age and sex adjustment at case-control analyses (odds ratio for illiterates = 1.4; 95% CI 0.6-3.1). In contrast, we found a significant association between manual principal lifetime occupation and dementia using both unadjusted and adjusted analyses (odds ratio = 2.9; 95% CI 1.2-7.4). Our findings suggest that, although education and occupation are related, occupation is a stronger indicator of risk than education.

A multicenter randomized trial of comprehensive geriatric assessment and management: experimental design, baseline data, and six-month preliminary results.

Between October 1992 and July 1993, 11 Northern Italian geriatric departments systematically screened 1386 inpatients hospitalized for at least 10 days. Of those screened, 74% (N = 1019) were excluded by one or more of 7 exclusion criteria; 32% (N = 118) of the 367 remaining subjects failed to meet more than 1 of 8 inclusion criteria. The 11 Geriatric Evaluation Units (GEUs) examined the remaining eligible 249 inpatients with a uniform comprehensive geriatric assessment (CGA) plan, which included a number of validated assessment scales. Of those evaluated, 39% (N = 97) were ineligible for the study because of being unwilling, noncompliant, too sick or "not truly frail", and the remaining 152 (11% of all patients screened) were randomly enrolled in two groups; 79 were assigned to the GEU (experimental group), and 73 to standard care in the National Health Care System (control group). At entry there was no statistically significant difference between the two groups. At 6 months, preliminary results are encouraging; GEU patients had a lower mortality than controls (2 vs 8, 2.5% vs 10.9%; p < 0.05). Slight differences were seen in both clinical-cognitive-affective-functional status and the use of health and social care resources. Only 3 subjects dropped out, 8 refused further follow-up, and 3 went to a nursing-home. We conclude that a standardized selection plan can recognize frail elderly inpatients and that GEU care seems to achieve good results.