ASSOCIATION OF VITAMIN D WITH MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DEMENTIA IN OLDER MEXICAN ADULTS.

BACKGROUND: It has been proposed that Vitamin D helps reduce the accumulation of cerebral ß-amyloid-42 by innate immune stimulation and phagocytosis activation. An association between low Vitamin D levels and Alzheimer's dementia (AD) has been established. We determined the association between Vitamin D, mild cognitive impairment (MCI), and AD in older Mexican adults (> 65 years). METHODS: Cross-sectional study conducted at the memory clinic in a tertiary-level hospital in Mexico City. We evaluated subjects with MCI, AD, and normal cognition (NC) with available serum Vitamin D [25(OH)D] levels (past 6 months). Three categories were assigned according to 25(OH)D levels: sufficiency (> 30 ng/mL), insufficiency (21-29 ng/mL), and deficiency (≤ 20 ng/mL). Descriptive statistics, means and standard deviations were used. Logistic regression analyses adjusted by age, sex, and educational level were performed. RESULTS: We evaluated 208 patients. Mean age was 79 ± 1 year, 65% (n = 136) were female; and mean educational level was 6.7 ± 2.3 years. Thirty-one subjects (14%) had NC; 42% (n = 88) had MCI; and 43% (n = 89) had AD. Prevalence of Vitamin D deficiency was 54%, more frequent in the AD group (64%) followed by the MCI (59%) and NC (13%) (p < 0.001) groups. In the multivariate logistic regression analysis, Vitamin D deficiency was associated with MCI (HR 25.02 [confidence interval 95% 4.48-139]; p < 0.001) and AD (HR 41.7 [5.76-301]; p < 0.001) after adjusting for confounders. CONCLUSIONS: Serum Vitamin D deficiency was associated with MCI and dementia; low levels produced a greater effect over executive functions.

Association of vitamin d with mild cognitive impairment and alzheimer's dementia in older mexican adults

ABSTRACT Background It has been proposed that Vitamin D helps reduce the accumulation of cerebral β-amyloid-42 by innate immune stimulation and phagocytosis activation. An association between low Vitamin D levels and Alzheimer’s dementia (AD) has been established. We determined the association between Vitamin D, mild cognitive impairment (MCI), and AD in older Mexican adults (> 65 years) Methods Cross-sectional study conducted at the memory clinic in a tertiary-level hospital in Mexico City. We evaluated subjects with MCI, AD, and normal cognition (NC) with available serum Vitamin D [25(OH)D] levels (past 6 months). Three categories were assigned according to 25(OH)D levels: sufficiency (> 30 ng/mL), insufficiency (21-29 ng/mL), and deficiency (≤ 20 ng/mL). Descriptive statistics, means and standard deviations were used. Logistic regression analyses adjusted by age, sex, and educational level were performed Results We evaluated 208 patients. Mean age was 79 ± 1 year, 65% (n = 136) were female; and mean educational level was 6.7 ± 2.3 years. Thirty-one subjects (14%) had NC; 42% (n = 88) had MCI; and 43% (n = 89) had AD. Prevalence of Vitamin D deficiency was 54%, more frequent in the AD group (64%) followed by the MCI (59%) and NC (13%) (p < 0.001) groups. In the multivariate logistic regression analysis, Vitamin D deficiency was associated with MCI (HR 25.02 [confidence interval 95% 4.48-139]; p < 0.001) and AD (HR 41.7 [5.76-301]; p < 0.001) after adjusting for confounders Conclusions Serum Vitamin D deficiency was associated with MCI and dementia; low levels produced a greater effect over executive functions.

Microparticles are related to cognitive and functional status from normal aging to dementia.

Recently, we have shown that microparticles (MPs) levels derived from leukocytes (LMPs), endothelium (EMPs), neurons (NMPs) and those expressing tissue factor (TFMPs) were higher in Alzheimer's Disease (AD) patients when compared to cognitively healthy subjects. Therefore, in this study we proposed to investigate the correlation between MPs levels, cognitive performance and functional status in a sample of elderly individuals. We evaluated MPs derived from platelets (PMPs), LMPs, EMPs, NMPs and TFMPs in 43 participants, of whom 12 with probable dementia due to AD, 16 with mild cognitive impairment (MCI) and 15 with no objective cognitive or functional impairment. PMPs, LMPs and TFMPs, were associated with cognitive impairment in this population. LMPs and NMP, were associated to lower functional performance in the elderly sample. These results suggest that MPs may be involved in the pathophysiology of neurodegenerative disorders.

The Roles of Physical Activity and Inflammation in Mortality, Cognition, and Depressive Symptoms Among Older Mexican Americans.

A higher level of physical activity (PA) is associated with decreased risk of mortality, dementia, and depression, yet the mechanisms involved are not well understood, and little evidence exists for Mexican Americans. With data from the Sacramento Area Latino Study on Aging (1998-2007), we used Cox proportional hazards regression to separately evaluate associations of baseline PA level with mortality, dementia/cognitive impairment without dementia (CIND), and depressive symptoms, and we estimated the mediating effects of inflammatory markers in additive hazard models. A low level of PA (<35 metabolic equivalent of task-hours/week) was associated with increased mortality (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.20, 1.88), dementia/CIND (HR = 1.37, 95% CI: 0.96, 1.96), and depressive symptoms (HR = 1.23, 95% CI: 1.00, 1.52). A low PA level added 512 (95% CI: -34, 1,058) cases of dementia/CIND per 100,000 person-years at risk (direct effect), while, through a mediating path, interleukin 6 (IL-6) added another 49 (95% CI: 5, 94) cases, or 9% of the total effect. For mortality, 8%-10% of the PA total effect was mediated through IL-6, tumor necrosis factor α (TNF-α), or TNF-α receptors. None of the inflammatory markers mediated the association between PA and depressive symptoms. Our results suggest that antiinflammation (especially as assessed by IL-6 and TNF-α levels) may partly explain how PA protects against dementia/CIND and mortality.

Hemostatic Abnormalities in Dementia: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) is considered the most frequent cause of dementia. It is known that vascular risk factors play an important role in the development and progression of this condition. Alterations in vascular walls represent documented findings in patients with AD and other dementias affecting elderly people. The authors performed a systematic review and meta-analysis, aiming to synthesize observational studies that evaluated how the hemostatic system may contribute to cognitive decline in the elderly, using papers published until April 2018 and as indexed in Medline (PubMed), Scopus, Web of Science, ScienceDirect, Lilacs, Cinahl, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Among 5,278 studies identified, 32 were included in the final synthesis, and these included 485 patients with mild cognitive impairment, 568 with vascular dementia (VD), 1,781 with AD, and 2,855 participants without dementia. AD patients had increased plasma von Willebrand factor (VWF) (standardized mean difference [SMD]: 2.53; 95% confidence interval [CI]: 0.10-4.95), D-dimer (SMD: 0.50; 95% CI: 0.35-0.66), plasminogen activator inhibitor-1 (SMD: 3.34; 95% CI: 1.01-5.67), thrombomodulin (SMD: 1.08; 95% CI: 0.53-1.62), and homocysteine levels (SMD: 0.65; 95% CI: 0.15-1.15). In contrast, the VD group showed increased fibrinogen levels (SMD: 0.77; 95% CI: 0.13-1.41), activated factor VII (SMD: 0.36; 95% CI: 0.05-0.67), factor VIII (SMD: 0.57; 95% CI: 0.22-0.91), VWF (SMD: 2.34; 95% CI: 0.38-4.29), D-dimer (SMD: 1.14; 95% CI: 0.51-1.78), and homocysteine (SMD: 2.17; 95% CI: 1.67-2.68). AD showed an elevation in some markers of endothelial dysfunction, whereas VD presented mostly an involvement of coagulation cascade components.

Prevalence of thyroid dysfunction and its impact on cognition in older mexican adults: (SADEM study).

INTRODUCTION: Subclinical thyroid dysfunction is a possible risk factor for cognitive impairment in old age, but results are inconsistent. Aim of the present study was to evaluate the prevalence of thyroid dysfunction among older community-dwelling adults and to see whether thyroid function impacts the cognitive status of the elderly. METHODS: We included 1750 participants from the Study on Aging and Dementia in Mexico (SADEM). All subjects were evaluated clinically via specific interviews. TSH levels were analyzed by chemiluminescent immunometry assay. We classified participants into five thyroid state groups: (1) normal TSH levels (0.40-4.0 IU/L) were considered euthyroid; (2) Overt hyperthyroidism: TSH <0.3 IU/l and FT4 >23 pmol/l; (3) Overt hypothyroidism: TSH >4.8 IU/l, FT4 <13 pmol/l; (4) Subclinical hyperthyroidism: TSH <0.3 IU/l, FT4: 13-23 pmol/l; (5) Subclinical hypothyroidism: TSH >4.8 IU/l, FT4: 13-23 pmol/l. RESULTS: The overall estimated prevalence of thyroid dysfunction in Mexican population was 23.7% (95% CI, 22.66-26.77). Of these, 15.4% older adults were classified as subclinical hypothyroidism, 7.2% overt hypothyroidism, 0.5% subclinical hyperthyroidism, and 0.6% overt hyperthyroidism. The association of thyroid dysfunction with cognitive impairment was most evident in overt hypothyroidism OR = 1.261 (1.185-1.343). CONCLUSIONS: The present study demonstrated a high prevalence of thyroid dysfunction in Mexican elderly people living in the community. A relationship between cognitive impairment and the presence of hypothyroidism was also shown, and to a lesser degree in hyperthyroidism.

Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms.

The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

Tight glycemic control and use of hypoglycemic medications in older veterans with type 2 diabetes and comorbid dementia.

OBJECTIVE: Older adults with diabetes and dementia are at increased risk for hypoglycemia and other adverse events associated with tight glycemic control and are unlikely to experience long-term benefits. We examined risk factors for tight glycemic control in this population and use of medications associated with a high risk of hypoglycemia in the subset with tight control. RESEARCH DESIGN AND METHODS: This retrospective cohort study of national Veterans Affairs (VA) administrative/clinical data and Medicare claims for fiscal years (FYs) 2008-2009 included 15,880 veterans aged ≥ 65 years with type 2 diabetes and dementia and prescribed antidiabetic medication. Multivariable regression analyses were used to identify sociodemographic and clinical predictors of hemoglobin A1c (HbA1c) control (tight, moderate, poor, or not monitored) and, in patients with tight control, subsequent use of medication associated with a high risk of hypoglycemia (sulfonylureas, insulin). RESULTS: Fifty-two percent of patients had tight glycemic control (HbA1c <7% [53 mmol/mol]). Specific comorbidities, older age, and recent weight loss were associated with greater odds of tight versus moderate control, whereas Hispanic ethnicity and obesity were associated with lower odds of tight control. Among tightly controlled patients, 75% used sulfonylureas and/or insulin, with higher odds in patients who were male, black, or aged ≥ 75 years; had a hospital or nursing home stay in FY2008; or had congestive heart failure, renal failure, or peripheral vascular disease. CONCLUSIONS: Many older veterans with diabetes and dementia are at high risk for hypoglycemia associated with intense diabetes treatment and may be candidates for deintensification or alteration of diabetes medications.

Fatty acid status and its relationship to cognitive decline and homocysteine levels in the elderly.

Polyunsaturated fatty acids (PUFAs), especially the n-3 series, are known for their protective effects. Considering that cardiovascular diseases are risk factors for dementia, which is common at aging, the aim of this study was to evaluate whether fatty acid status in the elderly was associated with cognitive function and cardiovascular risk. Forty-five elderly persons (age ≥ 60 years) were included and divided into two groups based on their Mini-Mental Status Examination score adjusted for educational level: the case group (n = 12) and the control group (n = 33). Serum fatty acid composition, homocysteine (Hcy), hs-CRP, lipid profile and different cognitive domains were evaluated. The case group, characterized by reduced cognitive performance, showed higher levels of 14:0, 16:0, 16:1n-7 fatty acids and lower levels of 22:0, 24:1n-9, 22:6n-3 (DHA) and total PUFAs compared to the control group (p < 0.05). The n-6/n-3 ratio was elevated in both study groups, whereas alterations in Hcy, hs-CRP and lipid profile were observed in the case group. Cognitive function was positively associated with the 24:1n-9, DHA and total n-3 PUFAs, while 14:0, 16:0 and 16:1n-7 fatty acids, the n-6/n-3 ratio and Hcy were inversely associated. In addition, n-3 PUFAs, particularly DHA, were inversely associated with cardiovascular risk, assessed by Hcy levels in the elderly.

High cortisol levels are associated with cognitive impairment no-dementia (CIND) and dementia.

BACKGROUND: This study aimed to compare serum cortisol concentrations in cognitively healthy elderly and in subjects with cognitive impairment no dementia (CIND) and dementia, besides to evaluate these concentrations according to apolipoprotein E genotype (APOE). METHODS: Three-hundred and nine elderly enrolled in the Pietà Study (Brazil) were divided in 3 groups: control (n=158), CIND (n=92) and dementia (n=59) and had concentrations of morning serum cortisol measured. Hormone concentrations were measured by chemiluminescence and APOE genotypes were determined by PCR followed by restriction fragment length polymorphism (RFLP). RESULTS: Medians of cortisol concentrations (µg/dl) for the groups were 12.14 (interquartile range - IQR 6.34) for control, 13.65 (IQR 5.88) for CIND and 14.47 (IQR 7.35) for dementia. Significant differences were observed for control vs. CIND (P=0.003), control vs. dementia (P=0.001), but not for CIND vs. dementia (P=0.269). No association was observed between cortisol concentrations and APOE genotype among the groups (P=0.348). CONCLUSIONS: The elevation in cortisol concentrations is associated with dementia, independently of APOE genotypes. Further studies are required to understand if elevation of cortisol is an initial event and how hippocampal damage and the loss of hypothalamus-pituitary-adrenal (HPA) axis inhibition may affect its concentrations.

Anemia and dementia among the elderly: the São Paulo Ageing & Health Study.

BACKGROUND: Anemia and dementia are common diseases among the elderly, but conflicting data are available regarding an association between these two conditions. We analyzed data from the São Paulo Ageing & Health Study to address the relationship between anemia and dementia. METHODS: This cross-sectional observational study included participants aged 65 years and older from a deprived area of the borough of Butantan, São Paulo, Brazil. Data about demographics, education, income, and cognitive and daily life function were collected, as well as blood samples. Anemia and dementia were defined according to WHO and DSM-IV criteria, respectively. RESULTS: Of the 2267 subjects meeting the inclusion criteria, 2072 agreed to participate in the study; of whom 1948 had a valid total blood count and were included in the analysis. Anemia was diagnosed in 203 (10.2%) participants and dementia in 99 (5.1%). The frequency of anemia was higher in patients with dementia according to univariate analysis (odds ratio (OR) = 2.00, 95% confidence interval (CI) = 1.17-3.41, p = 0.01), but this association was not present after adjusting for age (OR = 1.33, 95% CI = 0.76-2.33, p = 0.32). Further multivariate adjustment did not change the results. CONCLUSION: Although anemia and dementia are frequent disorders in older people, we found their relationship to be mediated exclusively by aging in this low-income population from São Paulo.

Sialic acid, homocysteine and CRP: potential markers for dementia.

To investigate whether sialic acid could discriminate between healthy age matched controls and patients with dementias of the Alzheimer's type (AD), and pure vascular dementia (VaD). 27 patients and 51 controls were administered the Mini-Mental State Examination (MMSE) and had blood analyzed for levels of total sialic acid, total homocysteine (tHcy), and C-reactive protein (CRP). Significant differences were found between the mean MMSE scores for patients with dementia compared with controls. Sialic acid levels were significantly higher in patients with AD compared with controls and homocysteine levels were higher in VaD. Sialic acid levels discriminated between patients with dementia of the Alzheimer's type and healthy controls only. The MMSE could discriminate between controls and patients with dementia but not between the subtypes and homocysteine was significant for patients with VaD.

Homocysteine (Hcy) and cognitive performance in a population sample of elderly Brazilians.

Hyperhomocysteinemia (HHcy) has been suggested as a predictive factor of cognitive alterations. Brazil has one of the highest aging dementia rates among the world's emerging countries. The objective of this study was to assess the influence of Hcy levels on the cognitive performance of low-income elderly. This cross-sectional study was developed in an urban center in the Northeast of Brazil and included 205 eligible community-dwelling older adults. A multidimensional questionnaire was used to evaluate sociodemographic aspects, health status and overall clinical aspects. Cognitive performance was assessed by the Portuguese version of Mini Mental State Examination (MMSE). Folic acid, vitamin B(12) and Hcy levels were determined by chemical luminescence. The association between sociodemographic variables, Hcy, serum vitamin B(12), folic acid levels and total MMSE score was assessed by multiple linear regression. Values indicative of HHcy (>12micromol/l) were found in 34.8% of the individuals. Age, schooling and HHcy showed a negative correlation with the MMSE score. The R(2) values of isolated HHcy explain only 4% of the MMSE score variance, however when associated to schooling and age, this model explained up to 25% of this association.

Vitamin B12 deficiency and dementia.

We set out to investigate the possible beneficial effects on cognitive function of demented patients with cobalamin deficiency after cobalamin replacement. A total of 181 consecutive, demented (DSM-III or DSM-III-R criteria and score below 24 on the Mini-Mental State Examination [MMSE]) outpatients (mean age 77.5 years) were prospectively evaluated and had their vitamin B12 level measured by radioimmunoassay. The frequency of vitamin B12 deficiency (less than 200 pg/mliter) was 25% (46 patients). Treatment outcome was obtained in 19 patients (19 of 46). Despite cobalamin replacement, 16 of 19 patients persisted in showing progressive decline during follow-up visits (3 to 24 months). The nonresponse to vitamin B12 replacement in most cases seems to reflect the presence of associated irreversible dementia or a follow-up of shorter duration in a few patients. All of the patients who showed some improvement (MMSE returned to normal values) had mild dementia with a history of less than 2 years. Thus, screening for B12 deficiency should be considered in patients with recent onset of mild mental status changes.

Copper-zinc superoxide dismutase activity in red blood cells and serum in demented patients and in aging.

The activity of the enzyme copper-zinc superoxide dismutase (Cu-Zn SOD) has been investigated in serum and red blood cells (RBC) homogenate obtained from demented patients with associated vascular lesions (VD), demented patients with probable Alzheimer's disease (DAT) and healthy controls (CG) of the same age. The increase in SOD activity was statistically significant (P < 0.01) in RBCs homogenate of DAT and VD patients, when compared to controls, but no differences appear between the two diseases groups. Additionally, a statistically significant increase in SOD activity (P < 0.01) in DAT patients above 70 years as compared to those 50-70 years old, and a relation between SOD and age were found. No changes in SOD activity with age in healthy controls nor in vascular dementia group were detected. A statistically significant increase in Circulating SOD activity (P < 0.01) was observed in vascular patients compared to controls. The observed increase in DAT Circulating SOD activity (against CG) was not significant. The increased levels of Cu-Zn SOD, probably represent a general alteration of the oxidative processes characteristic of these dementias and suggest that the enzyme might be used as a marker.