Correlates of delayed referral for the diagnosis of dementia in an outpatient population

BACKGROUND: Early diagnosis of dementia is critical, but there is usually a time lag between onset of symptoms and referral for neuropsychological testing and dementia diagnosis. We aimed to identify factors correlated with this delayed referral. METHODS: We studied 140 patients with cognitive deterioration referred to the Memory Clinic of the Catholic University (Rome) between 1995 and 1996. Alzheimer's disease or multi-infarct dementia was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and Hachinski ischemic score. Global cognitive and neuropsychological functions were assessed with the Mini-Mental State Exam (MMSE) and the Mental Deterioration Battery. The performance on the Activities of Daily Living was used to measure physical function. The time between onset of signs of cognitive deterioration and referral for diagnosis (time to diagnosis: TTD) was estimated through a semistructured interview of the caregiver. Independent correlates of TTD were identified after adjustment for potential confounders and stratifying patients based on level of physical function. RESULTS: Of 127 eligible patients, 63% had Alzheimer's disease, 26% multi-infarct dementia, and 11% had dementia of other types. Mean age was 73.9 +/- 8.2 years, and 59% of patients were females. The mean TTD was 13.8 +/- 10.8 months and did not differ by gender, household composition, or type of dementia. For patients with normal physical function, increased age (beta = .50), female sex (beta = .51), and low MMSE score (beta = .36) were associated with longer TTD. Among patients with physical impairment, only MMSE score showed an association with TTD, but it was of opposite direction (beta = -.31). These associations were consistent by type of dementia. CONCLUSIONS: Age, gender, and degree of cognitive impairment are important correlates of the time between onset of signs/symptoms and referral for dementia diagnosis. These factors are independent of the type of dementia but are influenced by the level of physical function.     

Serum testosterone levels and arterial blood pressure in the elderly.

The aim of this study was to evaluate the relationship between serum testosterone levels and arterial blood pressure (BP) in the elderly. We studied 356 non-diabetic, non-smoking, non-obese men aged 60 to 80 years and untreated for hypertension. All subjects were evaluated in the morning after an overnight fast. Evaluation included measurements of the following: BP (by mercury sphygmomanometer, Korotkoff I and V), body weight, height and free testosterone (T) plasma levels (by radioimmunoassay). According to the BP values, the subjects were classified as normotensives (NT; n=112; SBP/DBP<140/90 mmHg), systolic and diastolic hypertensives (HT; n=127; SBP/DBP>140/90 mmHg), and isolated systolic hypertensives (ISH; n=117; SBP>140 mmHg and DBP<90 mmHg). T values decreased with increasing age in all 3 groups and was significantly lower in HT (-15%) and ISH men (-21%) than in NT men (p<0.05). In each group, the T levels showed a highly significant negative correlation with BMI (p<0.001). A significant negative correlation was also found between T levels and SBP in NT (r=-0.35, p<0.001), ISH (r=-0.67, p<0.001), and HT (r=-0.19, p<0.05) men, whereas a negative correlation with DBP was observed only in the NT men (r=-0.19, p<0.05). Adjusting for the BMI confirmed a significant difference in plasma T levels between ISH and NT men, but not between HT and NT men. Multiple regression analysis employing BP as a dependent variable confirmed a strong relationship between T levels and SBP in all 3 groups, whereas a significant relationship between T levels and DBP was found only in NT men. In conclusion, although further studies are needed to clarify the relationship between plasma T levels and BP, our findings suggest that in elderly men with ISH, the reduced plasma levels of testosterone might contribute to the increased arterial stiffness typical of these subjects.     

Body mass index and mortality among hospitalized patients

BACKGROUND: Body mass index (weight in kilograms divided by the square of the height in meters [BMI]) is known to be associated with overall mortality. However, the effect of age on excess mortality from all causes associated with obesity is controversial. The aim of the present study is to determine the effect of age on the relationship between BMI and mortality. METHODS: We analyzed data from a large collaborative observational study group, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), that collected data on hospitalized patients. A total of 18,316 patients consecutively admitted to 79 clinical centers during 5 different surveys in 1998, 1991, 1993, 1995, and 1997 were enrolled in the present study. The main outcome measure was the relative hazard ratio of death for different levels of BMI. RESULTS: Mortality rate was lowest among men and women with BMIs from 25.0 through 27.4 kg/m(2) (relative risk, 0.24; 95% confidence interval, 0.15-0.38). The graphed relationship between BMI and mortality in younger patients was hyperbolic, with increased death rates at the lowest and highest BMI rankings. On the contrary, the older patients showed an increased death rate at the lowest BMIs with only a slight elevation at the highest BMIs (>35 kg/m(2)). CONCLUSIONS: Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among young and old hospitalized patients. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival. Furthermore, the finding of the high BMI associated with minimum hazard in elderly subjects supports some past findings and opposes others and, if confirmed, has important implications for geriatric clinical guidelines.     

Relationship between international normalized ratio values,vitamin K-dependent clotting factor levels and in vivo prothrombin activation during the early and steady phases of oral anticoagulant treatment

BACKGROUND AND OBJECTIVES: In vitro studies have shown that the rate of prothrombin activation is linearly related to the concentration of factor II (FII) in the assay system, suggesting a key role of prothrombin levels in the expression of the antithrombotic activity of oral anticoagulant treatment (OAT). We investigated the in vivo relationship between prothrombin activation and vitamin K-dependent clotting factor levels during the early and steady phases of OAT in patients and in healthy volunteers. DESIGN AND METHODS: The changes in international normalizezd ratio (INR) and in the plasma levels of FVII, FX, FII, protein C (PC) and prothrombin fragment 1.2 (F1+2) induced by OAT were monitored over 9 days in 10 patients not on heparin starting warfarin after heart valve replacement (HVR) and in 9 healthy volunteers submitted to an 8-day course of warfarin treatment. FII and F1+2 plasma levels were also measured in 100 patients on stable oral anticoagulant treatment with INRs ranging from 1.2 to 6.84. RESULTS: Because HVR patients had subnormal FVII, FX and FII levels after surgery, INR values > 2.0 were attained already 24 hours after the first warfarin dose. In healthy volunteers, INR values greater than 2.0 were first observed after 72 hours. Nadir levels of FVII, PC, FX and FII were reached between 40 and 88 hours in HVR patients and between 72 and 192 hours in healthy volunteers. The FII apparent half-disappearance time (t/2) was 99 hours in HVR patients and 115 hours in healthy volunteers (p = ns). In HVR patients there was no normalization of initially elevated F1+2 levels until day 7 with an apparent t/2 of 132 hours. In healthy volunteers, a decrease to subnormal F1+2 levels was observed by day 8 of treatment (apparent t/2 = 107 hours). In both HVR patients and healthy volunteers, FII and PC levels were independent predictors of the changes in F1+2 levels (p = 0.0001). In patients on stable OAT, only FII levels were independent predictors of the variation in F1+2 levels (p = 0.0001). INTERPRETATION AND CONCLUSIONS: During the early phase of oral anticoagulant treatment in vivo prothrombin activation is a function of the balance between FII and PC levels and is not significantly prevented until nadir levels of FII are obtained. This provides an explanation for the requirement of overlapping heparin and oral anticoagulant treatment for at least 48 hours after the achievement of therapeutic INR values in patients with thromboembolic diseases. In addition, in vivo prothrombin activation is a function of FII levels rather than INR values also in patients on stable oral anticoagulant treatment.     

Two peculiar cases of cranial fractures running through craniotomy burr holes: may this be a kind of “exception” to the Puppe rule

International Journal of Legal Medicine - A correct assessment on the position, path, and direction of fracture lines is crucial when the sequence of different injuries on the skull has to be...     

Taphonomic study on drowned victims in a non-sequestered aquatic environment in the Mediterranean Sea

International Journal of Legal Medicine - Human decomposition in sea water poses several challenges to forensic practitioners tasked with the analysis of drowned bodies. Postmortem changes in the...     

Dose-Related Impact of Alcohol Consumption on Cognitive Function in Advanced Age: Results of a Multicenter Survey

BACKGROUND: Moderate alcohol consumption has been associated in several studies with decreased risk of cardiovascular and cerebrovascular events; however, available data on the effects of alcohol intake on cognitive functioning are conflicting. We assessed the association between alcohol consumption and cognitive impairment in a series of older subjects enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association between average alcoholic intake and cognitive performance was assessed in 15,807 patients admitted to participating centers during the survey periods. Demographic variables, comorbid conditions, medications, and objective tests that were associated with cognitive impairment (as indicated by a Hodkinson Abbreviated Mental Test score <7) in separate logistical regression models were examined as potential confounders in a summary model. RESULTS: Cognitive impairment was detected in 1693 (19%) of 8755 drinkers and 2008 (29%) of 7052 nondrinkers (Fisher's exact test, p < 0.0001). After adjusting for potential confounders, alcohol consumption was associated with decreased probability of cognitive impairment (odds ratio, 0.75; 95% confidence interval, 0.66-0.85). The relationship between drinking level and cognitive dysfunction was nonlinear, because the probability of cognitive impairment was decreased for moderate alcohol use as compared with abstinence, but it was increased for daily consumption exceeding one wine-equivalent liter among men and 0.5 liter among women. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. CONCLUSIONS: Alcohol abuse is associated with increased prevalence of cognitive dysfunction among older subjects; however, a daily alcohol consumption of less than 40 g for women and 80 g or less for men might be associated with a decreased probability of cognitive impairment. This possible protective effect of alcohol consumption should be further assessed by prospective studies.     

Psychotropic medications and risk for falls among community-dwelling frail older people: an observational study

BACKGROUND: Injuries due to falls are one of the most important public health concerns for all ages, but especially for frail elderly people. Although a small number of falls have a single cause, the majority have many different causes resulting from the interactions between intrinsic or extrinsic risk factors. METHODS: We conducted an observational study on data from a large population of community-dwelling elderly people to tests the hypothesis that the current use of different classes of psychotropic medications, including antipsychotic agents, benzodiazepines, nonbenzodiazepine sedative-hypnotics, and antidepressants, increases the risk for falls. We analyzed data from a large collaborative observational study group, the Italian Silver Network Home Care project, that collected data on patients admitted to home care programs (n = 2854). RESULTS: After adjusting for all potential confounders, users of any psychotropic drugs had an increased risk of fall of nearly 47% (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.24-1.74). Similarly, compared with nonusers, users of atypical antipsychotic drugs also had an increased risk of falling at least once (OR, 1.45; 95% CI, 1.00-2.11). Among benzodiazepine users, patients taking agents with long elimination half-life (OR, 1.45; 95% CI, 1.00-2.19) and patients taking benzodiazepines with short elimination half-life (OR, 1.32; 95% CI, 1.02-1.72) had an increased risk of falls. Patients taking antidepressants did not show a higher risk of falling compared to nonusers (OR, 0.92; 95% CI, 0.83-1.41). CONCLUSIONS: Our data suggest that, among psychotropic medications, antipsychotic agents and benzodiazepines are associated with an increased risk of falls. Our findings do not support the hypothesis that preferential prescribing of short-acting benzodiazepines instead of long-acting agents or atypical antipsychotic medications instead of typical agents will substantially decrease fall risk associated with the use of these classes of drugs.