Cognitive Status According to Homocysteine and B-Group Vitamins in Elderly Adults.

OBJECTIVES: To determine the association between hyperhomocysteinemia and cognitive function, taking into account the effect of B group vitamin (BGV) deficiency. DESIGN: Cross-sectional. SETTING: Memory Clinic, S. Anna University Hospital, Ferrara, Italy. PARTICIPANTS: Elderly individuals (≥65) (N = 318; 44 normal cognition, 127 with cognitive impairment, 147 with dementia) divided into four groups according to plasma homocysteine (high vs normal) and BGV (normal vs deficit) levels. MEASUREMENTS: Cognitive, clinical, biochemical, functional, and neuroimaging parameters were evaluated. RESULTS: Hyperhomocysteinemia (>15 µmol/L) was associated with a higher prevalence of cognitive and functional impairment and dementia (odds ratio (OR) = 1.98, 95% confidence interval (CI) = 1.13-3.48), independent of BGV status and other confounders. Participants with hyperhomocysteinemia with normal BGV status had the worst functional status and the highest prevalence of dementia (high homocysteine/normal BGV vs normal homocysteine/normal BGV: OR = 3.20, 95% CI = 1.65-6.21). Homocysteine levels were correlated negatively with folate and vitamin B12 levels and glomerular filtration rate and positively with free thyroxine and uric acid levels (model coefficient of determination = 0.43). CONCLUSION: Hyperhomocysteinemia was associated with worse cognitive and functional status and dementia independently of BGV levels. Approximately half of participants with hyperhomocysteinemia had normal BGV levels, suggesting that other unmeasured factors might be associated with high homocysteine levels.

Serum levels of hydroperoxides and multimorbidity among older patients with mild cognitive impairment or late-onset Alzheimer's disease.

BACKGROUND: Oxidative stress (OxS) might be involved in the pathogenesis of late-onset Alzheimer disease (LOAD); noteworthy, the presence of multimorbidity is regarded as a common denominator of OxS and dementia. AIM: To evaluate the contribution of multimorbidity to OxS in LOAD and mild cognitive impairment (MCI). METHODS: Serum hydroperoxides and multimorbidity (CIRS-CI scale) were evaluated in 46 Controls, 104 MCI and 75 LOAD. RESULTS: A trend toward an increase of hydroperoxides from Controls to MCI to LOAD was observed (LOAD vs Controls p = 0.01). This OxS marker was positively and significantly correlated with CIRS-CI in Controls (p = 0.002) and patients with MCI (p = 0.005) but not in those with LOAD (p = 0.104). CONCLUSIONS: Multimorbidity is associated with systemic OxS but only in elderly people with either no or mild cognitive impairment. Although OxS is elevated in LOAD patients, its association with multimorbidity seems to be negligible, confirming the existence of strong disease-specific pro-oxidant mechanisms.

Systemic oxidative stress and conversion to dementia of elderly patients with mild cognitive impairment.

Mild cognitive impairment (MCI) is regarded as a prodromal phase of late onset Alzheimer's disease (LOAD). It has been proposed that oxidative stress (OxS) might be implicated in the pathogenesis of LOAD. The aim of this study was to investigate whether a redox imbalance measured as serum level of hydroperoxides (i.e., by-products of lipid peroxidation) and/or serum antioxidant capacity might be predictive of the clinical progression of MCI to LOAD. The levels of these two markers were measured in 111 patients with MCI (follow-up: 2.0 ± 0.6 years), 105 patients with LOAD, and 118 nondemented healthy controls. Multivariate analysis adjusted for potential confounding factors, including age, gender, smoking, and comorbidities, showed a significant increase (P < 0.05) in baseline levels of OxS in MCI and LOAD as compared to cognitive healthy controls. No differences in either of OxS markers were found by comparing MCI patients who converted (n = 29) or not converted (n = 82) to LOAD. Overall, these results suggest that systemic OxS might be a precocious feature of MCI and LOAD. However, the role of OxS as an early prognostic marker of progression to LOAD needs further investigations.

Oxidative balance, homocysteine, and uric acid levels in older patients with Late Onset Alzheimer's Disease or Vascular Dementia.

This study aimed to investigate whether Late Onset Alzheimer's Disease (LOAD) and Vascular Dementia (VAD) might be associated with a distinct profile of oxidative stress (OxS) peripheral markers. Serum levels of hydroperoxides, homocysteine, advanced oxidation protein products, uric acid, thiols, and total and residual antioxidant power were assessed in 103 mild cognitive impairment (MCI), 89 LOAD, 54 VAD patients and 48 Controls. Compared with Controls, a similar oxidative unbalance (high hydroperoxides and low residual antioxidant power) was observed in MCI, LOAD and, although less pronounced, VAD. Moreover, individuals with simultaneously high levels of homocysteine and uric acid, both well-known risk factors for cardiovascular disease, had a high probability to be affected by VAD (O.R.:10.50; 95% C.I.: 2.33-47.2), but not LOAD (O.R.: 3.0; 95% C.I.:0.86-10.76) compared with individuals with normal values. Our data suggest that, although they might share a common OxS-related pathogenesis, VAD and LOAD might maintain some distinctive features, with a predominance of "vascular component" in VAD compared with LOAD.

Subsyndromal delirium and its determinants in elderly patients hospitalized for acute medical illness.

BACKGROUND: In older individuals, acute medical illnesses and admission to hospital are often associated with a deterioration of cognitive status, also in the absence of dementia and full-blown delirium. We evaluated the prevalence of subsyndromal delirium (SSD) and its correlates in a sample of elderly medical inpatients. METHODS: From 763 consecutive inpatients, 325 participants with known dementia or delirium were excluded, whereas 438 (mean age: 80.6 years; female participants: 60.1%) were enrolled. SSD was diagnosed within 48 hour from admission, when at least two DSM-IV delirium criteria including disorientation, attention or memory deficit, altered level of consciousness, or perceptual disturbances were present. Cognitive performance was evaluated by Mini Mental Status Examination (MMSE). General, clinical, and laboratory parameters were also registered. RESULTS: One hundred and sixty-six patients (37%) had SSD. Compared with controls, SSD patients were older individuals, had less formal education, higher comorbidity, lower hemoglobin/lymphocytes counts, and higher creatinine levels. A trend toward higher prevalence of previous stroke and widowhood was observed. A MMSE score of less than 24/30 identified SSD with 88% sensitivity and 78% specificity. In SSD patients, MMSE independently correlated with years of education, high-sensitivity C reactive protein levels, and O2 arterial saturation (model adjusted r (2) = 0.30, p = .001); conversely, only years of education were associated with MMSE in controls (adjusted r (2) = 0.06, p = .01). CONCLUSIONS: Our data suggest that SSD is common in hospitalized older medical inpatients, and low MMSE score might be useful for identification of participants at risk of SSD. Current inflammatory response and reduced O2 arterial saturation were the only independent determinants of cognitive performance in SSD patients.

Systemic oxidative stress in older patients with mild cognitive impairment or late onset Alzheimer's disease.

A large body of evidences obtained in human and animal brain tissue suggest a role of oxidative stress (OxS) in the pathogenesis of late onset Alzheimer's disease (LOAD); on the contrary, data on peripheral markers of OxS in LOAD are still controversial. We evaluated the serum levels of products of lipid peroxidation, hydroperoxides, advanced oxidation protein products, total and residual antioxidant power, thiols, and uric acid in a sample of 334 older individuals: 101 LOAD patients, 134 patients with mild cognitive impairment (MCI), and 99 controls. At univariate analysis, serum hydroperoxides were higher while residual antioxidant power was lower in MCI and LOAD compared with in controls. By multivariate logistic regression analysis we found that, compared with controls, high levels (over median value) of serum hydroperoxides were independently associated with an increase in the likehood of having MCI (Odd Ratio: 2.59, 95% Confidence Interval: 1.08-6.21) or LOAD (OR: 4.09, 95%CI: 1.36-11.81). Furthermore, low levels of residual antioxidant power (below the median value) were associated with increased risk of having MCI (OR: 3.97, 95% CI: 1.62-9.72), but not dementia (OR: 2.31, 95%CI: 0.83-6.63). Our study suggests that a systemic redox-imbalance leading to OxS might be associated not only with LOAD but also with MCI.

Prior antiplatelet drug use and short-term mortality in older patients with acute ischemic stroke (AIS).

Some studies suggest that previous treatment with antiplatelet agents (AA) might reduce ischemic stroke severity and improve outcomes in terms of clinical deficits or mortality. We evaluated the effect of the prior chronic use of AA on short-term (30 days) mortality in a sample of consecutive patients with AIS. Four hundred thirty-nine older patients (>65 years) with "major" AIS (modified Rankin scale ≥ 3) consecutively admitted to the University ward of Internal Medicine or Geriatrics were enrolled. Stroke was classified according to Oxfordshire Community Stroke Project (OCSP). Data recorded included: (1) clinical features; (2) medical history including home therapies, and vascular risk factors; (3) routine clinical chemistry analyzes (verb)/analyses (noun). Short-term (30 days) mortality was 27.6%. One hundred fifteen subjects (26.2%) were taking AA before admission. Compared with subjects not treated, subjects taking AA were characterized by higher prevalence of recurrent stroke (35% vs. 22%). In this group, a trend toward a higher prevalence of congestive heart failure (CHF), smoking, and altered levels of consciousness (ALC) was noted. Stroke type and short-term mortality (33% vs. 26.2%; odds ratio=OR=1.25; 95% confidence interval=CI=0.75-2.10, age and gender adjusted) were not different between the two groups. Adjustment for glucose, CHF, previous stroke, smoking, and ALC did not change mortality risk (OR=0.83; 95%CI=0.40-1.72). We conclude that in older patients hospitalized for "major" AIS, prior use of AA was not associated with any benefit in terms of short-term mortality both in patients with first, as well as in those with recurrent ischemic stroke.