Valeria Nativio

Education, Occupation, and Prevalence of Dementia: Findings from the Conselice Study

Information about the epidemiology of dementia in Italy is still limited, although this cognitive disorder represents a serious public health concern. We estimated the prevalence of dementia and dementia subtypes in the elderly population of a Northern Italian municipality, Conselice, in the Emilia Romagna region (n = 1,016 subjects aged 65–97 years). The associations of dementia with two modifiable risk factors, education and occupation, were also evaluated. Overall dementia prevalence was 5.9% (95% confidence interval 4.3–7.8), exponentially increased with age, and was higher among women. Of the dementia cases, 50% were Alzheimer’s disease (AD), but an unusually high prevalence (45%) was found for vascular dementia (VD). After adjustment for age and gender, education but not occupation was associated with both AD and VD. This association could not be explained by occupation, life habits, and previous history of hypertension or cardiovascular disease.

Dehydroepiandrosterone-sulfate serum levels and common age-related diseases: results from a cross-sectional Italian study of a general elderly population.

The association of low serum dehydroepiandrosterone sulfate (DHEAS) levels with age, lifestyle, general health status indicators, and specific diseases was investigated in 436 men and 544 women of 65-97 yr old. In both sexes low serum DHEAS levels were associated with age, alcohol intake, number of current medications, and decreased thyroid function. Low DHEAS was also associated with low serum albumin in men and low systolic blood pressure in women. Compared to healthy men (n=106) age-adjusted serum DHEAS levels were significantly lower in men with atrial fibrillation, chronic obstructive lung disease, dementia, parkinsonism, cancer, diabetes, hypothyroidism, and in institutionalized men. Compared to healthy women (n=100) age-adjusted serum DHEAS levels were significantly lower in women with occlusive arterial disease, chronic obstructive lung disease, and osteoporosis. After controlling for differences in lifestyle and general health status parameters, low DHEAS levels remained statistically associated only with atrial fibrillation in men and osteoporosis in women, and it cannot be excluded that these association were spurious, due to multiple comparisons. These data suggest that in elderly people low serum DHEAS levels are more a non-specific indicator of aging and health status than a risk indicator of specific diseases.

Independent predictors of ischemic stroke in the elderly: Prospective data from a stroke unit

ABSTRACT Objective: Incidence of ischemic stroke (IS) increases with age. Knowledge of factors associated with IS acute outcomes in the oldest-old (≥80 years) is needed to improve quality of care and resource allocation in this age group. Methods: Data are for 769 consecutive IS patients aged ≥60 years (436 aged ≥80 years) admitted to an Italian stroke unit in a 4-year period. Demographics, prestroke disability (modified Rankin Scale ≥3) and comorbidities, IS etiology and subtype, NIH Stroke Scale (NIHSS) score, clinical and laboratory admission parameters, and medical complications were prospectively registered. Independent predictors of in-hospital death, incident disability, length of stay, discharge without rehabilitation, and no direct discharge home were identified by multiple logistic regression. Risk profiles before and after age 80 were compared. Results: Poor outcomes were more frequent in the oldest-old compared to the younger patients. NIHSS score, clinical parameters of IS severity (need for oxygen, indwelling catheter, or nasogastric tube), incident disability, and medical complications predicted most of the study outcomes in both age groups. After age 80, IS etiology and subtype proved additional independent determinants for most outcomes along with age, sex, and prestroke functional and health status. Conclusions: Characteristics related to neurologic impairment on admission were the main predictors of acute outcomes of IS in this cohort. Specific IS etiology and subtype influenced IS outcomes only after age 80. In oldest-old patients, demographics and prestroke functional and health status also influenced IS outcomes with peculiar associations.

The Clock-Drawing Test in Elderly Italian Community Dwellers: Associations with Sociodemographic Status and Risk Factors for Vascular Cognitive Impairment

To evaluate whether performance in the clock-drawing test (CDT) is associated with sociodemographic status and risk factors for cognitive impairment, we examined 744 Italian community dwellers aged ≧65 (73 ± 6) years scoring ≧24 on the MMSE. CDT was scored by two different methods, the Sunderland and the Wolf-Klein methods. Sociodemographic, lifestyle, clinical and biochemical variables were also recorded. For both scoring methods, lower CDT scores were associated with age, poor education, increased serum C-reactive protein and history of cancer. Associations of lower CDT scores with increased serum glucose and history of cerebrovascular disease were also found for the method with the highest sensitivity to cognitive impairment. This study shows that in elderly community dwellers, CDT may be not totally free from sociodemographic biases, and that it is associated with risk factors for cognitive impairment and frailty.

Plasma amino acid concentrations in healthy and cognitively impaired oldest-old individuals: associations with anthropometric parameters of body composition and functional disability.

Only a few reports exist of plasma amino acid profiles in the oldest-old, and none exist of the oldest-old with cognitive problems. Therefore, we measured fasting plasma amino acid concentrations in twenty-three healthy community-dwellers aged 90-103 years (group A); eighteen community-dwellers with mild cognitive impairment without dementia aged 91-104 years (group B); thirty-three patients with dementia aged 96-100 years (group C); and sixty healthy young controls aged 20-50 years. Biochemical and anthropometric parameters, and the basic activities of daily living (ADL) were also measured. Independent of cognitive status, in all oldest-old groups, essential:non essential amino acids (EAA:NEAA) was lower than in young controls and positively associated with body muscle mass. Patients with dementia were further characterized by a negative association between EAA:NEAA and the number of dependent ADL. All oldest-old groups had higher values of tyrosine:other large neutral amino acids (LNAA) than young controls. Groups B and C also had a higher phenylalanine:other LNAA. These data show that abnormalities in plasma amino acid profile are common in oldest-old individuals independent of their cognitive status, but that, in oldest-old patients with dementia, they are associated with functional disability. The abnormalities in phenylalanine and tyrosine plasma availability could contribute to the cause or aggravation of concurrent cognitive problems because these amino acids are neurotransmitter precursors and compete with other LNAA for transport into the brain.

Thyroid function tests and early outcomes of acute ischemic stroke in older euthyroid patients

Blood thyroid function tests (TFT) are routinely used to screen for thyroid disorders in several clinical settings. TFT on hospital admission may also be useful prognostic predictors of acute IS: according to recent evidence, poststroke outcome is better in patients with lower thyroid function and worse in those with higher thyroid function. However, previous reports are few and mostly compared patients with thyroid disorders to euthyroid patients. Thyroid disorders are known risk factors for cerebrovascular disease. However, hyperthyroidism is related to cardioembolic IS whereas hypothyroidism is related to atherosclerotic risk factors. Therefore, findings from available studies of TFT might just reflect the worse prognosis of cardioembolic IS compared to other IS subtypes. Another limitation of previous studies is the lack of information for older persons, who represent three quarters of all IS patients. In this paper, we investigated whether serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) measured on Stroke Unit (SU) admission are associated with early outcomes of acute IS in 775 euthyroid patients aged ≥65 years (mean age 80.1±8.7 years). Two composite outcomes were investigated: poor functional outcome (death during SU stay or disability at SU discharge), and unfavorable discharge setting (death during SU stay, transfer from SU to other acute hospital unit or transfer from SU to long-term care-facilities as opposed to direct discharge home). Analyses were performed using logistic regression models. Curvilinear associations were tested including TFT as polynomial terms. Models were adjusted for demographics, prestroke, and IS-related confounders. We found that lower TSH had a complex curvilinear association with poor functional outcome and that the shape of the associations changed with age. At age 65, the curve was U-shaped: outcome risk decreased with increasing TSH, reached its minimum at TSH near 3.00mUI/L and then started to rise. Between ages 70 and 75, however, the shape of the curve straightened and, starting from age 80 took an inverted U-shape: outcome risk rose with increasing TSH, reached its maximum at TSH values that progressively shifted upward with increasing age (from 1.70mU/L at age 80 to about 2.20mUI/L at age 90), then started to decrease. A linear inverse association was found between FT3 and unfavorable discharge setting. Our study suggests that measurement of TFT on SU admission can provide independent prognostic information for early outcomes of acute IS in older euthyroid patients.

The Effect of Age on Characteristics and Mortality of Intracerebral Hemorrhage in the Oldest-Old.

Background: Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (<65 years), young-old (65-74 years) and old-old (75-84 years) subjects. We also investigated whether age is an independent mortality predictor in elderly (age ≥65 years) subjects with acute ICH. Methods: We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. Results: Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had the highest admission hematoma volume (p < 0.01). Age was unrelated to all other ICH characteristics including HE. In elderly patients, multivariable adjusted risk of in-SU and 1-year mortality did not vary across age categories. Conclusions: Oldest-old subjects with acute supratentorial ICH have higher admission hematoma volume than young and young-old subjects but do not differ for other ICH characteristics. When taking into account confounding from ICH characteristics, risk of in-SU and 1-year mortality in elderly subjects with acute supratentorial ICH does not differ across age categories. Our findings question use of age as an independent criterion for stratification of mortality risk in elderly subjects with acute ICH.

Mortality After Admission to Stroke Unit for Intracerebral Hemorrhage: Effect of Age 80 and Older and Multimorbidity

To the Editor: The incidence of spontaneous intracerebral hemorrhage (ICH) increases exponentially with age, so individuals aged 80 and older are expected to represent a growing proportion of all people admitted to stroke units (SU) for ICH. Age of 80 and older is considered to be a major predictor of ICH mortality independent of characteristics related to ICH severity, but supporting evidence is limited to two small noncontemporary cohort studies and a large contemporary cohort study that did not control for any confounders. Findings from noncontemporary cohorts may not be applicable to individuals with ICH currently benefiting from organized inpatient (SU) care, which has improved ICH survival. Another limitation of these studies is the lack of control for prestroke multimorbidity, which is a known predictor of mortality in stroke. This prospective study investigated whether, in individuals with ICH admitted to a SU, age of 80 and older predicts in-SU mortality independent of multimorbidity. The study included 213 participants aged 80 and older (mean age 84.9 4.0, 57.9% male) and 259 participants younger than 80 (mean age 68.7 9.9, 39.9% male) with spontaneous first-episode ICH consecutively admitted to the SU of the Maggiore Hospital (Bologna, Italy) between October 2007 and December 2013. The Maggiore Hospital ethics committee approved the study. All participants (or their representatives) provided informed consent. Information was collected from medical records. Multimorbidity was defined as a Charlson Comorbidity Index of 2 or greater. Other confounders were sex, hypertension, diabetes mellitus, atrial fibrillation, dementia, prestroke functional impairment (modified Rankin Scale), neurological impairment on admission (National Institutes of Health Stroke Scale), anticoagulation-related etiology, pulse pressure, neuroradiological findings (location and intraventricular extension), and recourse to neurosurgical procedures. The association between aged 80 and older and in-SU mortality was estimated using hazard ratios (HRs) and their 95% confidence intervals (CIs) from Cox proportional hazards regression models adjusted for prestroke and ICH-related confounders. Preliminary analyses showed a significant interaction between age and multimorbidity (P = .04). Based on inspection of survival curves and on previous literature, the interaction was modeled as a time-dependent variable to obtain separate mortality risk estimates for stays or 7 or fewer days and longer than 7 days. Analyses were performed using SPSS version 21 (IBM Corp., Armonk, NY). P < .05 was considered statistically significant. Mortality at 7 days or fewer (69.3% of all deaths) was unrelated to age or multimorbidity (Table 1). By contrast, mortality at longer than 7 days was six times as high for younger than 80 with multimorbidity and aged 80 and older with and without multimorbidity than for younger than 80 without multimorbidity. In individuals with stroke, deaths within the first week are mostly the direct consequence of hemorrhagic injury, whereas deaths in the following weeks are mostly related to medical complications. Therefore, age 80 and older and multimorbidity may fail to affect in-SU mortality during the first week because, at this time, prognosis mainly depends on ICH severity, but after the first week, age 80 and older and multimorbidity may become relevant for managing medical complications. Nevertheless, in the model, the effect of multimorbidity was limited to individuals younger than 80. It may be that, in individuals aged 80 and older, the direct consequences of hemorrhagic injury override those of medical complications for a longer time than in younger individuals. Age-related alterations in cellular architecture and the metabolism of the human brain that may aggravate hematoma expansion and perihematomal edema are consistent with this hypothesis. Moreover, animal models show that brain hemorrhage in older age is associated with excess

Supplementary Material for: The Effect of Age on Characteristics and Mortality of Intracerebral Hemorrhage in the Oldest-Old

BACKGROUND Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (<65 years), young-old (65-74 years) and old-old (75-84 years) subjects. We also investigated whether age is an independent mortality predictor in elderly (age ≥65 years) subjects with acute ICH. METHODS We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. RESULTS Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had the highest admission hematoma volume (p < 0.01). Age was unrelated to all other ICH characteristics including HE. In elderly patients, multivariable adjusted risk of in-SU and 1-year mortality did not vary across age categories. CONCLUSIONS Oldest-old subjects with acute supratentorial ICH have higher admission hematoma volume than young and young-old subjects but do not differ for other ICH characteristics. When taking into account confounding from ICH characteristics, risk of in-SU and 1-year mortality in elderly subjects with acute supratentorial ICH does not differ across age categories. Our findings question use of age as an independent criterion for stratification of mortality risk in elderly subjects with acute ICH.