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.

Endogenous sex hormones as risk factors for dementia in elderly men and women.

BACKGROUND: The associations of endogenous sex hormones with risk of dementia in the elderly population are not well known. METHODS: The relationship of baseline serum total estradiol (E2) and free testosterone (FT) to 4-year risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) was examined in a dementia-free, population-based cohort of 433 women (mean age 74 years) and 376 men (mean age 73 years). Multivariable proportional hazards regression was used to adjust for sociodemographic and lifestyle variables, body mass index, apolipoprotein E genotype, cardiovascular conditions, and homocysteinemia. RESULTS: Dementia developed in 71 women (46 AD, 21 VaD) and 39 men (23 AD, 12 VaD). In women with high E2 (serum E2 >or= 10 pg/mL), the multivariable-adjusted hazard ratio (HR) for dementia was 1.75 (95% confidence interval [CI], 1.06-2.89). The corresponding multivariable-adjusted HR for AD was 1.94 (95% CI, 1.04-3.61), whereas no association was found for VaD. No association with dementia was found for serum FT in women and for either serum E2 or FT in men. CONCLUSION: High serum E2 is an independent predictor for dementia and AD in elderly women.

Blood inflammatory markers and risk of dementia: The Conselice Study of Brain Aging.

Incidence studies of blood inflammatory markers as predictors of dementia in older age are few and did not take into account hyperhomocysteinemia, although this condition is associated with both inflammation and increased risk of dementia. We investigated the relationships of baseline serum C-reactive protein (CRP), serum interleukin 6 (IL6), plasma alpha-1-antichymotrypsin, and hyperhomocysteinemia (defined as plasma total homocysteine>15 micromol/L) with risk of incident Alzheimer's disease (AD) and vascular dementia (VaD) in a dementia-free Italian population-based elderly cohort (n=804, 53.2% women, mean age 74 years) with 4 years of follow-up. No inflammatory marker, alone or in combination, predicted AD risk whereas the combination of high CRP and high IL6 was associated with risk of VaD (HR, 2.56; 95%CI, 1.21-5.50) independently of socio-demographic confounders, traditional risk factors and hyperhomocysteinemia. By contrast, in the same model, hyperhomocysteinemia was independently associated with AD (HR, 1.91; 95%CI, 1.02-3.56) but not VaD risk. Blood inflammatory markers are associated with increased VaD risk but do not predict AD, which seems selectively associated with hyperhomocysteinemia.

Apolipoprotein E e4 allele affects risk of hyperhomocysteinemia in the elderly.

BACKGROUND: Apolipoprotein E (APOE) plays a central role in VLDL metabolism. Both APOE e4 allele (APOE4) and C-reactive protein (CRP) are associated with greater risk of dementia and vascular disease, but APOE4 carriers have lower blood concentrations of CRP than do noncarriers, possibly through a mechanism favoring the clearance of the CRP VLDL-bound fraction. Homocysteine, another risk factor for vascular disease and dementia, also binds to VLDL in blood. However, the association between APOE4 and hyperhomocysteinemia has never been thoroughly investigated. OBJECTIVE: We investigated in an elderly population whether 1) APOE4 is associated with hyperhomocysteinemia [plasma total homocysteine (tHcy) > 15 micromol/L], 2) hyperhomocysteinemia affects the association between APOE4 and high CRP (serum CRP > 3 mg/L), and 3) B vitamin status affects these associations. DESIGN: APOE4 genotypes were assessed and tHcy, CRP, and serum concentrations of folate and vitamin B-12 were measured in 671 cognitively healthy subjects (52% women; mean age: 73 y) from an Italian population-based prospective cohort study. RESULTS: APOE4 carriers without high CRP [multivariate-adjusted odds ratio (OR): 0.22; 95% CI: 0.08, 0.59] had a lower risk of hyperhomocysteinemia than did noncarriers. The risk of high CRP was lower in APOE4 carriers without hyperhomocysteinemia (multivariate-adjusted OR: 0.51; 95% CI: 0.31, 0.85) than in noncarriers. The associations were not affected by B vitamin status. CONCLUSION: Independently from B vitamin status, APOE4 carriers have a lower risk of hyperhomocysteinemia and of high CRP than do noncarriers, but the presence of one condition attenuates the association of APOE4 with the other condition.

Metabolic Syndrome: prevalence and prediction of mortality in elderly individuals.

OBJECTIVE: Little is known about the prevalence of the metabolic syndrome among elderly people in Italy, its association with all-cause mortality, and whether measurement of serum C-reactive protein (CRP) and interleukin (IL)-6 affects this association. RESEARCH DESIGN AND METHODS: The baseline prevalence of metabolic syndrome, diagnosed according to the National Cholesterol Education Program (NCEP) criteria, and all-cause mortality at 4 years were recorded in an Italian population-based cohort (981 subjects, 55% women, aged 65-97 years). A Cox model adjusted for sociodemographic, lifestyle, and medical variables was used to investigate 1) whether metabolic syndrome was a predictor of mortality and 2) how the association was affected by baseline high CRP (>3 mg/l) and IL-6 (>1.33 pg/ml). RESULTS: Overall, metabolic syndrome prevalence was 27.2% [95% CI 24.0-30.5] and higher in women (33.3% [28.7-38.0]) than in men (19.6% [15.5-24.2]). During follow-up, 137 deaths occurred. Using the no metabolic syndrome/no high IL-6 group as the reference, mortality was not associated with the metabolic syndrome alone (multivariable-adjusted hazard ratio 1.24 [0.60-2.59]), only weakly associated with high IL-6 alone (1.66 [1.04-2.63]), but strongly associated with the concurrent presence of metabolic syndrome and high IL-6 (3.26 [2.00-5.33]). High CRP was not a mortality predictor (0.83 [0.58-1.20]) nor did it affect the association of the other variables with mortality. CONCLUSIONS: Metabolic syndrome by NCEP criteria is highly prevalent in the Italian elderly population. It is not itself associated with mortality but may improve the usefulness of IL-6 as a mortality predictor in older age.

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.

Interleukin-1beta and interleukin-6 gene polymorphisms as risk factors for AD: a prospective study.

Risk of incident dementia from any cause and Alzheimer's disease (AD) in relation to the IL-1beta-511 (C-->T) and IL-6-174 (G-->C) polymorphisms was investigated in an Italian elderly cohort (n=791) with 4 years of follow-up. Analyses were adjusted for socio-demographic confounders (age, gender, education), presence of the Apolipoprotein E-epsilon4 allele, and plasma total homocysteine (tHcy), a newly proposed AD risk factor. No significant association was found for the IL-1beta-511 and IL-6-174 polymorphisms with either dementia or AD. However, in the baseline dementia-free cohort considered as a whole, independently of other confounders, IL-1beta-511 T/T homozygotes had lower plasma tHcy than both heterozygotes (P=0.036) and wild-types (P=0.004). These data do not support the hypothesis that the IL-1-beta-511 and IL-6-174 polymorphisms affect dementia or AD risk. The relationship between the AD risk factor plasma tHcy and the IL-1beta-511 polymorphism was never reported before and might explain previous cross-sectional reports of an association between this polymorphism and AD.