A comparison of frailty indexes for prediction of adverse health outcomes in an elderly cohort.

This study aimed to compare the predictive accuracy for several frailty-related adverse health outcomes of a cumulative index derived from the Italian population-based elderly cohort of the Conselice Study of Brain Aging (CSBA), which takes into account multiple different domains (demographic, clinical, functional, and nutritional parameters), with that of an index derived from the Study of Osteoporotic Fractures (SOF), modified for application to the CSBA database and henceforth called mSOF, which is exclusively focused on muscular fitness. Data are for 1007 CSBA participants aged ≥ 65 years. Investigated adverse outcomes included 4- and 7-year risk of death and 4-year risk of fractures, falls, disability, hospitalization, and nursing home placement. Accuracy for prediction of these outcomes was investigated using area under the curve (AUC) statistics. CSBA index performed better than mSOF index for prediction of mortality (p<0.001), hospitalization (p=0.002), and nursing home placement (p=0.049). For all outcomes excluding falls, frailty defined by CSBA index had a slightly lower specificity but a much higher sensitivity than frailty defined by mSOF Index. In conclusion, in this elderly cohort, the multidimensional CSBA index is a better predictor of frailty-related adverse health outcomes than the unidimensional mSOF index.

Serum thyroid-stimulating hormone as a predictor of cognitive impairment in an elderly cohort.

BACKGROUND: It is unclear whether in late life serum thyroid-stimulating hormone (TSH) predicts risk of developing cognitive impairment. OBJECTIVE: This study investigated the prospective relationship of serum TSH with the risk of developing mild cognitive impairment (MCI), Alzheimer's disease (AD) and vascular dementia (VaD) in an elderly cohort with a 4-year follow-up. METHODS: Data are for 660 subjects aged 65 years and older from an Italian population-based cohort who were cognitively normal at an extensive assessment in 1999/2000 and underwent follow-up assessment in 2003/2004. Serum TSH was measured at baseline. Multinomial logistic models adjusted for sociodemographic and cardiovascular risk factors were used to investigate the association of serum TSH (both as a tertile and continuous log-transformed variable) with risk of incident MCI, AD and VaD diagnosed according to international criteria. RESULTS: Over 3.8 ± 0.7 years of follow-up, there were 149 incident MCI cases (77 with impairment of memory and 72 with impairment of nonmemory domains) and 86 incident dementia cases (53 with AD, 28 with VaD). No association between baseline TSH and risk of developing any MCI subtype or AD was found. The highest TSH tertile had a threefold higher increased risk of VaD (OR: 3.25, 95% CI: 1.01-10.77, p = 0.048) compared to the lowest tertile. Risk of VaD increased about 60% for each 1 SD increase in log-transformed TSH (OR: 1.61, 95% CI: 1.06-2.44, p = 0.025). CONCLUSIONS: In this elderly cohort, baseline TSH was not related to the risk of developing MCI or AD, but high TSH was associated with an increased risk of VaD. These results suggest further need for research using larger samples to examine the role of TSH as a predictor of VaD and the role of thyroid autoimmunity in vascular cognitive impairment.

Diagnostic performance of an Executive Clock Drawing Task (CLOX) as a screening test for mild cognitive impairment in elderly persons with cognitive complaints.

BACKGROUND: CLOX, a clock drawing test protocol uniquely sensitive to impairment of executive functions, has been proposed as a screening tool for mild cognitive impairment (MCI), but data about its diagnostic efficiency are lacking. METHODS: There are data for 196 subjects, age >or=60 years, referred to a memory clinic for cognitive complaints. After extensive neuropsychological testing, 64 were diagnosed as cognitively normal and 132 with MCI. RESULTS: At standard cutoffs, both CLOX subtests had a fair specificity (CLOX1 72%, CLOX2 92%) but unacceptably low values of sensitivity (CLOX1 54%, CLOX2 28%) and likelihood ratio (CLOX1 1.91, CLOX2 3.59) for MCI. The use of different cutoffs or the combination of CLOX with the Mini-Mental State Examination (MMSE) did not statistically increase diagnostic efficiency. CONCLUSION: CLOX, either alone or in combination with MMSE, is not a useful screening test for MCI in a clinical setting.

Metabolic syndrome and risk of dementia in older adults.

OBJECTIVES: To investigate the association between metabolic syndrome (MetS; a clustering of cardiovascular risk factors including abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, each of which has been individually associated with dementia) and incident dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in older adults before and after the age of 75. DESIGN: Prospective population-based cohort. SETTING: An Italian municipality. PARTICIPANTS: A community-based sample of 749 subjects aged 65 and older who, in 1999/2000, were free of cognitive impairment and, in 2003/04, underwent follow-up for incident dementia. MEASUREMENTS: The relationship between incident overall dementia, AD, and VaD and MetS. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. MetS was defined according to the National Cholesterol Education Program criteria. RESULTS: Risk of overall dementia and its subtypes was not associated with MetS or any MetS component in participants younger than 75. In participants aged 75 and older, MetS was associated with a lower risk of AD (hazard ratio (HR)=0.33, 95% confidence interval (CI)=0.12-0.94) but not of VaD, and abdominal obesity was associated with a lower risk of overall dementia (HR=0.53, 95% CI=0.28-0.98). CONCLUSION: MetS measured in late life is not associated with risk of dementia. After age 75, persons with MetS may even be at lower risk for AD.

Blood inflammatory proteins and risk of incident depression in the elderly.

BACKGROUND: It is unclear whether high levels of blood inflammatory proteins are associated with the risk of developing depression in late life. METHODS: Blood C-reactive protein, interleukin (IL)-6, 1 -antichymotrypsin (ACT), intercellular adhesion molecule 1, and tumor necrosis factor were measured in an elderly cohort (n = 968). Major depression diagnosed according to clinical criteria and relevant depressive symptoms measured by the Geriatric Depression Scale (score 6 10) were assessed at baseline and 4 year later. RESULTS: Baseline IL-6 and ACT were increased in both prevalent major depression and relevant depressive symptoms. Baseline ACT was increased in incident major depression. All associations weakened below significance after adjustment for possible confounders and multiple comparisons. CONCLUSIONS: Blood inflammatory proteins do not predict the risk of developing depression in older age.

Blood homocysteine and risk of depression in the elderly.

We studied whether increased blood homocysteine is a predictor for incident depression in a population-based cohort aged >or=65. A total of 240 men and 217 women were identified at baseline and were assessed 4 years later for depression (Geriatric Depression Scale, GDS >or=10 or use of antidepressants). Risk of incident depression was estimated for the highest gender-specific tertile of baseline plasma homocysteine compared to the other tertiles combined in a reference group. As deficiencies of B(12) and folate are the main determinant of increased blood homocysteine in old age, serum concentrations of these vitamins were also measured. In women only, the highest homocysteine tertile was associated with incident depression. However, women with combined serum B(12)/folate deficiency had the highest blood homocysteine but also a lower depression risk than vitamin-replete women. In conclusion, the data only moderately support the hypothesis that blood homocysteine is a predictor of depression.

Prevalent depressive symptoms as a risk factor for conversion to mild cognitive impairment in an elderly Italian cohort.

OBJECTIVE: To examine the association between depressive symptoms and prevalent and incident mild cognitive impairment (MCI) in elderly individuals; to verify whether it is affected by MCI subtype. DESIGN: Prospective, population-based, longitudinal cohort study. SETTING: Adults >or=65 years resident in an Italian municipality. PARTICIPANTS: Baseline data are for 595 subjects with no cognitive impairment (NCI) and 72 subjects with prevalent MCI. NCI subjects underwent a 4-year follow-up for incident MCI. MEASUREMENTS: MCI was diagnosed according to international criteria and classified as with (m + MCI) or without memory impairment (m - MCI). Baseline depressive symptoms were measured using the 30-item Geriatric Depression Scale (GDS). Baseline use of antidepressants was also recorded. RESULTS: Baseline depressive symptoms (GDS >or=10) were more frequent in prevalent MCI cases (44.4%) than in NCI participants (18.3%). The association was independent of MCI subtype, antidepressant use, and sociodemographic and vascular risk factors. In NCI subjects, baseline depressive symptoms were also associated with increased risk of MCI at follow-up, but only for subjects on antidepressant drugs at baseline (incident cases = 72.7%) compared with those without depressive symptoms and not on antidepressant therapy (incident cases = 24.0%). The association was independent of other confounders and stronger for m - MCI (incident cases = 45.4%) with respect to m + MCI (incident cases = 27.3%). CONCLUSIONS: Depressive symptoms are highly prevalent among elderly MCI subjects and, in cognitively normal elderly individuals, are associated with an increased risk of developing MCI. The association is stronger for the MCI subtype without memory impairment.

Plasma tocopherols and risk of cognitive impairment in an elderly Italian cohort.

BACKGROUND: Evidence that vitamin E may preserve cognitive function in elderly subjects is conflicting. The most abundant and most investigated form of vitamin E in humans is alpha-tocopherol, but other antioxidant tocopherols (beta, gamma, and delta) exist in nature. OBJECTIVE: We aimed to investigate plasma concentrations of the natural tocopherols and the tocopherol oxidation markers alpha-tocopherylquinone (alphaTQ) and 5-nitro-gamma-tocopherol (5NGT) in relation to cognitive function in the elderly. DESIGN: Baseline plasma tocopherols and their oxidation markers were measured in 761 elderly Italian subjects from a population-based cohort assessed in 1999-2000 for mild cognitive impairment (MCI) and dementia. In 2003-2004, information about cognitive status was collected for 615 of the 666 subjects without baseline cognitive impairment. Tocopherols and oxidation markers were analyzed as plasma absolute values divided by serum total cholesterol because lipids affect their blood availability. Analyses were adjusted for sociodemographic, genetic, lifestyle, and medical confounders. RESULTS: Compared with the corresponding lowest tertile, the risk of prevalent dementia was higher for the highest tertile of delta-tocopherol/cholesterol [odds ratio (OR): 3.87; 95% CI: 1.46, 10.27] and alphaTQ/cholesterol (4.02; 1.45, 11.14), but the risk of incident dementia was not directly associated with plasma vitamin E metabolites. A U-shaped association, with lower risk for intermediate tertiles, was found for prevalent MCI with 5NGT/cholesterol (0.39; 0.17, 0.91) and for incident dementia with gamma-tocopherol/cholesterol (hazard ratio: 0.42; 95% CI: 0.22, 0.84). CONCLUSIONS: Plasma concentrations of some non-alpha-tocopherol forms of vitamin E are associated with cognitive impairment in elderly people. However, the associations depend on concurrent cholesterol concentration and need further investigation.

Development of an easy prognostic score for frailty outcomes in the aged.

BACKGROUND: identification of frailty is recommended in geriatric practice. However, there is a lack of frailty scores combining easy-to-collect predictors from multiple domains. OBJECTIVE: to develop a frailty score including only self-reported information and easy-to-perform standardised measurements recommended in routine geriatric practice. DESIGN: prospective population-based study. SETTING/PARTICIPANTS: included 1,007 Italian subjects aged 65 and over. MEASUREMENTS: seventeen baseline possible mortality predictors from several domains, 4-year risk of mortality and other adverse health outcomes associated with frailty [fractures, hospitalisation, and new and worsening activities of daily living (ADL) disability]. METHODS: a multivariate Cox model was used to identify the best sub-group of independent predictors and to develop a mortality prognostic score, defined as the number of adverse predictors present. Logistic regression was used to verify whether the score also predicted risk of other frailty outcomes in the cohort survivors. RESULTS: nine independent mortality predictors were identified. Among subjects with score > or =3, each one point increase in the score was associated with a doubling in mortality risk and, among survivors, with an increased risk of all the other adverse health outcomes. CONCLUSIONS: nine easy-to-collect predictors may identify aged people at increased risk of adverse health outcomes associated with frailty.

Mild cognitive impairment: epidemiology and dementia risk in an elderly Italian population.

OBJECTIVES: To investigate prevalence and incidence of mild cognitive impairment (MCI) and its risk of progression to dementia in an elderly Italian population. DESIGN: Longitudinal. SETTING: Population-based cohort aged 65 and older resident in an Italian municipality. PARTICIPANTS: A total of 1,016 subjects underwent baseline evaluation in 1999/2000. In 2003/04, information about cognitive outcome was collected for 745 participants who were free of dementia at baseline. MEASUREMENTS: MCI (classified as with or without impairment of the memory domain), dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) diagnosed according to current international criteria. RESULTS: Overall prevalence of MCI was 7.7% (95% confidence interval (CI)=6.1-9.7 %) and was greater with older age and poor education. During 4 years of follow-up, 155 incident MCI cases were diagnosed, with an incidence rate of 76.8 (95% CI=66.8-88.4) per 1,000 person-years. Approximately half of prevalent and incident MCI cases had memory impairment. Compared with normal cognition, multivariable-adjusted risk for progression from MCI with memory impairment to dementia was 4.78 (95% CI=2.78-8.07) for any dementia, 5.92 (95% CI=3.20-10.91) for AD, and 1.61 (95% CI=0.37-7.00) for VaD. No association with dementia risk was found for MCI without memory impairment. Approximately one-third of MCI cases with memory impairment did not progress to dementia. CONCLUSION: MCI occurs often in this elderly Italian cohort and is associated with greater risk of AD, but only when the impairment involves the memory domain. However, a substantial proportion of MCI cases with memory impairment do not progress to dementia.

Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment.

OBJECTIVES: Mild cognitive impairment (MCI) is regarded as a precursor to dementia, but not all patients with MCI actually develop dementia. As Alzheimer and vascular dementia are thought to share many common etiopathogenetic mechanisms, we investigated whether the vascular risk factor atrial fibrillation affects the risk of conversion to dementia for different MCI subtypes diagnosed according to international criteria. METHODS: One hundred and eighty elderly outpatients with MCI and 431 elderly outpatients with a normal cognition were followed up for a mean of 3 and 4 years, respectively. The risk of conversion to dementia associated with atrial fibrillation was studied in both samples using a Cox proportional hazards model adjusted for socio-demographic and medical variables. RESULTS: Overall conversion rate to dementia was 10.5 (8.0-13.8 per 100 person-years) in the MCI group and 2.2 (1.5-3.1 per 100 person-years) in the normal cognition group. Atrial fibrillation was significantly associated with conversion to dementia [hazard ratio (HR): 4.63; 95% confidence interval: 1.72-12.46] in the MCI group but not in the cognitively normal group (HR: 1.10; 95% confidence interval: 0.40-3.03). DISCUSSION: Current diagnostic criteria for MCI subtypes define heterogeneous populations, but atrial fibrillation can be useful in identifying people with increased risk of conversion to dementia.