Ora Lux

The Sydney Memory and Ageing Study (MAS): methodology and baseline medical and neuropsychiatric characteristics of an elderly epidemiological non-demented cohort of Australians aged 70-90 years.

BACKGROUND The Sydney Memory and Ageing Study (Sydney MAS) was initiated in 2005 to examine the clinical characteristics and prevalence of mild cognitive impairment (MCI) and related syndromes, and to determine the rate of change in cognitive function over time. METHODS Non-demented community-dwelling individuals (N = 1037) aged 70-90 were recruited from two areas of Sydney, following a random approach to 8914 individuals on the electoral roll. They underwent detailed neuropsychiatric and medical assessments and donated a blood sample for clinical chemistry, proteomics and genomics. A knowledgeable informant was also interviewed. Structural MRI scans were performed on 554 individuals, and subgroups participated in studies of falls and balance, metabolic and inflammatory markers, functional MRI and prospective memory. The cohort is to be followed up with brief telephone reviews annually, and detailed assessments biannually. RESULTS This is a generally well-functioning cohort mostly living in private homes and rating their health as being better than average, although vascular risk factors are common. Most (95.5%) participants or their informants identified a cognitive difficulty, and 43.5% had impairment on at least one neuropsychological test. MCI criteria were met by 34.8%; with 19.3% qualifying for amnestic MCI, whereas 15.5% had non-amnestic MCI; 1.6% had impairment on neuropsychological test performance but no subjective complaints; and 5.8% could not be classified. The rate of MCI was 30.9% in the youngest (70-75) and 39.1% in the oldest (85-90) age bands. Rates of depression and anxiety were 7.1% and 6.9% respectively. CONCLUSIONS Cognitive complaints are common in the elderly, and nearly one in three meet criteria for MCI. Longitudinal follow-up of this cohort will delineate the progression of complaints and objective cognitive impairment, and the determinants of such change.

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-1β, -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.

Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample.

BACKGROUND Case control studies have supported a relationship between low folic acid and vitamin B112 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.

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

Objectives 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. Methods 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. Results 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. Conclusions 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.

Factors Predicting Reversion from Mild Cognitive Impairment to Normal Cognitive Functioning: A Population-Based Study

Introduction 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. Methods 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. Results 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). Discussion 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.

Risk profiles of subtypes of mild cognitive impairment: the sydney memory and ageing study.

To compare the risk profiles of mild cognitive impairment (MCI) subtypes in a population‐based elderly sample.

Risk Factors for Late-Life Cognitive Decline and Variation with Age and Sex in the Sydney Memory and Ageing Study

Introduction An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline. Methods Participants were 889 community-dwelling 70–90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined. Results All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7–49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine. Discussion Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits.

Risk profiles for mild cognitive impairment vary by age and sex: the Sydney Memory and Ageing study.

OBJECTIVES : To examine age- and sex-related differences in risk and protective factors for mild cognitive impairment (MCI) in community-based elderly individuals. DESIGN : Cross-sectional study. SETTING : The population-based Sydney Memory and Ageing Study. PARTICIPANTS : A total of 757 nondemented, community-dwelling elderly individuals from an English-speaking background categorized as younger (70-79 years) or older (80-90 years). MEASUREMENTS : Risk of MCI was determined for sociodemographic, lifestyle, and cardiac, physical, mental, and general health factors using age- (and sex-) adjusted multiple regressions comprising initially significant univariate factors. RESULTS : The point prevalence of MCI within our sample was 39.1% overall: it was lowest in younger women (32.3%) and similar across men and older women (41.9%-43.6%). The risk of MCI across all participants was increased by the APOE ∊4 allele, high homocysteine, and heart disease; and decreased by better odor identification, visual acuity, and mental activity. Risk factors in all younger participants were slow 6-m walk, poor odor identification, and high homocysteine. Risk of MCI was associated in younger women with history of depression, less mental activity, slower 6-m walk, poorer visual acuity, and higher homocysteine; and in younger men with poorer odor identification and higher homocysteine. Older participants showed no significant risk factors for MCI, except for poorer visual acuity in men. Supporting these findings were statistically significant interactions that reflected the differences in risk factor profiles between age and/or sex groups. CONCLUSIONS : Risk factors for MCI differ in men and women and vary with age. This has implications for preventing MCI and possibly dementia.

Associations between plasma antioxidants and hypertension in a community-based sample of 415 Australians aged 60–64

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.

The effect of vitamin C and E supplementation on lipid and urate oxidation products in plasma

Abstract Plasma malondialdehyde (MDA) and allantoin concentrations were measured in fifteen volunteers before and after ingestion of either vitamin C, vitamin E or both. Increasing doses in the range of 250 – 1000mg for vitamin C and 200 – 800 I.U. for vitamin E were used over a period of eight weeks. Our study showed that an intake of 250mg vitamin C and 200 I.U. vitamin E produced a 25% reduction allantoin levels, doubling the dose resulted in a 75% reduction. Supplementation with both vitamins produced the earliest reduction in allantoin levels. Combined administration of both vitamins or vitamin C on its own, resulted in a reduction of MDA levels in plasma. Current recommended dietary allowances are discussed in relation to the supplementation doses used in this study.