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.

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.

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.

Serum C-reactive protein and cognitive function in healthy elderly Italian community dwellers.

BACKGROUND: Chronic low-grade inflammation, as measured with the peripheral serum marker C-reactive protein (sCRP), may be a risk factor for dementia in elderly persons. METHODS: The relationship between sCRP and score on the Mini-Mental State Examination (MMSE), a commonly used screening cognitive measure, was investigated in 540 well functioning, healthy, and cognitively normal elders (age 73 +/- 6 years). Sociodemographic status, lifestyle, health status, traditional and nontraditional cardiovascular risk factors including plasma total homocysteine (tHcy), and other peripheral blood markers of vascular inflammation (leukocyte count, serum albumin, and plasma fibrinogen) were also assessed. RESULTS: Risk for having sCRP in the highest decile (>0.7 mg/dl) was significantly higher in individuals with MMSE score 24-25 (odds ratio = 3.07, 95% confidence interval, 1.2-7.9) and 26-28 (odds ratio = 2.10, 95% confidence interval, 1.1-3.9) compared with those scoring above 28 (reference group). Results were unaffected by adjustment for all potential confounders. No association was found between MMSE and peripheral markers of vascular inflammation other than sCRP, but lower MMSE scores were also independently associated with hyperhomocysteinemia (plasma tHcy > 15 mmol/L). CONCLUSION: In healthy, cognitively normal elderly community dwellers, increased sCRP levels are associated with concurrent cognitive impairment as measured by MMSE. The association is independent of sociodemographic status, lifestyle, health status, and traditional and nontraditional cardiovascular risk factors including hyperhomocysteinemia. Results support the hypothesis that chronic low-grade inflammation may be involved in age-related cognitive impairment.

Associations of the -174 G/C interleukin-6 gene promoter polymorphism with serum interleukin 6 and mortality in the elderly.

Serum interleukin-6 (sIL6) is an acknowledged predictor of all-cause mortality in older age. A common G/C polymorphism has been identified at position -174 of the IL6 gene promoter (IL6-174G>C), but its associations with sIL6 and mortality are still unclear. Data from a population-based elderly cohort (n=824) were used to study the associations of baseline sIL6 with the IL6-174 C-allele (C+) carrier status and all-cause mortality at 4 years, in the presence and absence of preexisting major diseases (PMD). Analyses were adjusted for socio-demographic factors and body-mass-index. Three-hundred-eighty-eight participants (47.1%) had PMD. Compared to the bottom sIL6 quartile, mortality increased both in presence [Hazard Ratio (HR)=3.04; 95% confidence interval (CI): 1.48-6.25] and absence of PMD [HR=3.91; 95%CI: 1.42-10.72] for the third higher sIL6 quartile, but only in presence of PMD for the top sIL6 quartile [HR=2.30; 95%CI: 1.09-4.83]. In absence of PMD, C+ carrier status did not affect both sIL6 and mortality. In presence of PMD, C+ carrier status was associated with increased baseline sIL6 [odds ratio 2.01; 95%CI: 1.25-3.22, for all sIL6 quartiles above the bottom] but not with increased mortality risk. A survival advantage was even found for C+ carriers with PMD and sIL6 in the top quartile [HR=0.31, 95%CI: 0.13-0.76]. In conclusion, although associated with increased sIL6 levels in presence of major diseases, the IL6-174 C-allele does not seem to have direct detrimental effects on survival in older age.