Peripheral blood markers of inflammation and functional impairment in elderly community-dwellers.

The cross-sectional association of functional impairment with several peripheral blood inflammatory markers (increased C-reactive protein (CRP), fibrinogen and leucocyte count, decreased cholesterol and albumin) was studied in 739 elderly community-dwellers. Functional measures included Tinetti test for gait and balance, and basic and Instrumental Activities of Daily Living. When considering each marker individually, only increased CRP was inversely associated with all functional measures independently of demographics, lifestyle, and comorbidity (P < 0.05). When considering the sum of positive markers, having more than one marker was also inversely associated with all functional measures (P < 0.05), but no clear gradient of impairment was found across increasing numbers of markers. When considering specific combinations of markers, having both increased CRP and at least another positive marker had a stronger association with functional impairment (P < 0.01 for all measures) than increased CRP alone (P > 0.05), or other positive markers alone or in combination (P < 0.05). In conclusion, in elderly individuals, peripheral blood markers of inflammation are associated with functional impairment independently of potential confounders. A specific combination of CRP with other markers provides a better correlate of functional impairment than both individual markers or a simple count of positive markers.

Common polymorphisms in methylenetetrahydrofolate reductase (MTHFR): relationships with plasma homocysteine concentrations and cognitive status in elderly northern italian subjects.

Hyperhomocysteinemia may be a risk factor for cognitive impairment. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine (Hcy) metabolism. Both the MTHFR 677C-->T and the 1298A-->C polymorphisms are associated with mild hyperhomocysteinemia, particularly in conditions of low folate status. The prevalence of these MTHFR polymorphisms and their relationships with plasma total Hcy (tHcy), serum folate and cognitive function was evaluated in 194 elderly Italian individuals: 122 healthy controls (73.8 +/- 7.1 years of age), 24 cognitively- impaired- not-demented individuals (78.6 +/- 9.3 years), and 48 subjects with Alzheimer dementia (AD = 26), vascular dementia (VD =22; 85.5 +/- 7.0 years). Twenty-one percent of all subjects were homozygous for 677C-->T and 7 % for 1298A-->C polymorphism. No significant relationship was found betweenMTHFR polymorphisms and age, cognitive status and type of dementia. Plasma tHcy did not differ significantly by MTHFR genotypes, but, subjects of all genotypes with low serum folate (<12 nmole/l) had higher plasma tHcy (p < 0.001), than subjects with high serum folate (>= 12 nmole/l). The study suggests that 677C-->T and 1298A-->C polymorphisms are common in the Northern Italian population, but do not significantly affect plasma tHcy levels of elderly individuals, even under conditions of low folate status. The lack of association of age and cognitive function with MTHFR genotypes argues against a negative selection for these polymorphisms.

Homocysteine and cognitive performance in healthy elderly subjects.

Hyperhomocysteinemia is a risk factor for dementia but only scanty data exist about its relationship to specific cognitive abilities during normal aging. We recruited 62 healthy and cognitively normal subjects of age 65-91 years from the Conselice Study of brain aging. The following neuropsychological tests were applied (i) The mental deterioration battery(MDB) consisting of 7 parts: the Rey's 15 words immediate and delayed recall, word fluency, sentence construction, Raven's progressive matrices '47, immediate visual memory, freehand copying of drawings and copying drawings with landmarks. (ii) The Prose memory test. (iii) The Corsi block-tapping task. (iv) The mini mental state examination(MMSE) scores. We measured plasma total homocysteine (tHcy), serum folate, vitamin B12 and plasma vitamin B6. Multivariate-adjusted linear regression analysis showed statistically significant negative association of plasma tHcy with scores at MMSE (b= -0.01 2,p < 0.001) and word fluency (b = -0.009, p = 0.021). A non-significant trend towards a negative association was also found for sentence construction (b = -0.006, p = 0.076). One can conclude that in healthy elderly subjects, increased plasma tHcy is correlated to poorer performance at a specific measure of language abilities being compromised in both vascular and Alzheimer's dementia. The study suggests that plasma tHcy could be an early marker of cognitive impairment.

Plasma homocysteine and inflammation in elderly patients with cardiovascular disease and dementia.

Increased levels of plasma total homocysteine (tHcy) may play a role in both cardiovascular diseases (CVD) and old-age dementias via enhancement of vascular inflammation. However, the association between plasma tHcy and serum C-reactive protein (sCRP), taken as a marker of low-grade inflammation, is still uncertain. We investigated this association in normal aging, CVD, and dementia, and examined whether it was modified by the presence of two major comorbid diseases of older age: chronic obstructive pulmonary disease (CPOD) and peptic ulcer (PU). Six hundred-twenty-seven individuals aged > or = 65 yr (74+/-7 yr) were selected for this study: 373 healthy controls; 160 patients with CVD but no evidence of comorbid diseases (CVD+/comorbidity-); 46 patients with CVD and concurrent CPOD and/or PU (CVD+/comorbidity+); and 48 patients with dementia. A positive association between plasma tHcy and serum CRP, independent of several confounders (socio-demographic status, known tHcy and sCRP determinants, inflammation markers, traditional vascular risk factors), was found for CVD+/comorbidity+ (p=0.001; not affected by dementia type) and dementia (p=0.001; not affected by dementia type), but not for CVD+/comorbidity- and controls. The results suggest that the association between plasma tHcy and sCRP is more an aspecific reflection of poor health than a specific correlate of vascular inflammation.