Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

<div><h3>Objectives</h3><p>Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort.</p> <h3>Methods</h3><p>664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique.</p> <h3>Results</h3><p>At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years.</p> <h3>Conclusions</h3><p>Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.</p> </div

Associations between plasma antioxidants and hypertension in a community based sample aged 60- 64 years

It has been suggested that increased oxidative stress may be both a cause as well as a consequence of hypertension. In vivo oxidation of low-density lipoproteins by oxygen-free radicals may increase hypertension-related atherogenesis, and antioxidants may be beneficial in this regard. Previous findings concerning associations between serum measures of antioxidants; and hypertension have however been inconsistent. Plasma levels of β-carotene, Vitamin A, E, uric acid, homocysteine and total antioxidant capacity, as well as two markers of oxidative stress, malondialdehyde (MDA) and protein carbonyls, were measured in morning fasting blood samples provided by 415 Australians aged 60-64 years, selected randomly from the community. Participants also provided information on sociodemographic attributes, mental and physical health, and provided two measures of resting blood pressure, allowing a diagnosis of definite or borderline hypertension. Those with hypertension had lower levels of β-carotene and higher levels of uric acid and MDA compared to normotensive participants. The last two of these associations persisted when the analyses controlled for lifestyle and health factors. The findings from this study offer limited support for the proposition that lower antioxidant status and higher oxidative stress are associated with hypertension, and suggest the need for longitudinal studies to examine causality and intervention studies to determine the benefit of antioxidants in this group

Hormone replacement therapy, brain volumes and white matter in postmenapausal women aged 60-64

Research on the structural and functional effects of hormone replacement therapy on the brain has produced inconsistent results. This paper reports on cross-sectional associations between hormone replacement therapy use and volumes of brain structures measured using magnetic resonance imaging in 213 postmenopausal women aged 60-64 years recruited from a large population study. Of these, 64 were current hormone replacement therapy users, 69 previous users and 80 had never used hormone replacement therapy. No differences were observed between groups in total grey matter, white matter, hippocampal or amygdalar volumes, severity or volume of white matter hyperintensities, or in different measures of brain atrophy. While acknowledging the limitations of a cross-sectional study, the results argue against hormone replacement therapy being protective against brain changes associated with ageing in women in their early 60s

Relationship of homocysteine, folic acid and vitamin B12 with depression in middleaged community sample

Background. Case control studies have supported a relationship between low folic acid and vitamin B12 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations. Method. A random subsample of 412 persons aged 60-64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging. Results. Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. Conclusions. Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct

Inflammatory biomarkers predict depressive, but not anxiety symptoms during aging : the prospective Sydney Memory and Aging Study

This study addresses the paucity of research on the prospective relationship between a range of inflammatory markers and symptoms of depression and anxiety during aging. In the Sydney Memory and Aging Study, the relationships between remitted depression, current and first onset of symptoms of depression or anxiety (Geriatric Depression Scale and Goldberg Anxiety Scale (GDS, GAS), and markers of systemic inflammation (C-reactive protein (CRP), interleukins-1b, -6, -8, -10, -12, plasminogen activator inhibitor-1 (PAI-1), serum amyloid A, tumor necrosis factor-α, and vascular adhesion molecule-1) were investigated. The sample consists of N = 1037 non-demented community-dwelling elderly participants aged 70—90 years assessed at baseline and after 2-years. All analyses were adjusted for gender, age, years of education, total number of medical disorders diagnosed by a doctor, cardiovascular disorders, endocrine disorders, smoking, body mass index, currently using anti-depressants, NSAIDS or statins and diabetes mellitus. The results show a significant linear relationship between increasing levels of IL-6 and depressive symptoms at baseline only, whereas IL-8 was associated with depressed symptoms at baseline and at 2 years follow-up. In addition, IL-8 was associated with first onset of mild to moderate depressive symptoms over 2 years. Logistic regression analyses showed that PAI-1 (OR = 1.37, 95% CI = 1.10—1.71, p = 0.005) was associated with remitted depression. Results for anxiety symptoms were negative. The findings are suggestive of IL-6 and IL-8 being associated with current symptoms and IL-8 being associated with first onset of depressive symptoms, whereas PAI-1 could be regarded as a marker of remitted depression

Homocysteine and the Brain in Midadult Life : Evidence for an increase risk of leukoaraiosis in men

Background: High serum homocysteine (HCY) levels have been associated with thromboembolic cerebrovascular disease, but their relationship to microvascular disease is uncertain. Homocysteine also has a direct neurotoxic effect and has been linked to brai

Factors predicting reversion from mild cognitive impairment to normal cognition: a population-based study.

Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition.Our analyses considered 223 participants (48.9% male) aged 71-89 years, drawn from the prospective, population-based Sydney Memory and Ageing Study. All were diagnosed with MCI at baseline and subsequently classified with either normal cognition or repeat diagnosis of MCI after two years (a further 11 participants who progressed from MCI to dementia were excluded). Associations with reversion were investigated for (1) baseline factors that included diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and physical and mental health; (2) longitudinal change in potentially modifiable factors.There were 66 reverters to normal cognition and 157 non-reverters (stable MCI). Regression analyses identified diagnostic features as most predictive of prognosis, with reversion less likely in participants with multiple-domain MCI (p = 0.011), a moderately or severely impaired cognitive domain (p = 0.002 and p = 0.006), or an informant-based memory complaint (p = 0.031). Reversion was also less likely for participants with arthritis (p = 0.037), but more likely for participants with higher complex mental activity (p = 0.003), greater openness to experience (p = 0.041), better vision (p = 0.014), better smelling ability (p = 0.040), or larger combined volume of the left hippocampus and left amygdala (p<0.040). Reversion was also associated with a larger drop in diastolic blood pressure between baseline and follow-up (p = 0.026).Numerous factors are associated with reversion from MCI to normal cognition. Assessing these factors could facilitate more accurate prognosis of individuals with MCI. Participation in cognitively enriching activities and efforts to lower blood pressure might promote reversion