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.
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.
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.
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.
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.
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.
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.
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.
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.
: To examine age- and sex-related differences in risk and protective factors for mild cognitive impairment (MCI) in community-based elderly individuals.
: Cross-sectional study.
: The ...population-based Sydney Memory and Ageing Study.
: 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).
: 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.
: 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.
: Risk factors for MCI differ in men and women and vary with age. This has implications for preventing MCI and possibly dementia.
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.
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.
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.
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.
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.
Inflammation may contribute to cognitive decline and dementia. This study examined the cross-sectional relationships between markers of systemic inflammation (C-reactive protein, interleukins-1β, -6, ...-8, -10, -12, plasminogen activator inhibitor, serum amyloid A, tumour necrosis factor-α and vascular adhesion molecule-1) and cognitive function in 873 non-demented community-dwelling elderly participants aged 70–90 years. Regression analyses were performed to determine the relationships between cognitive domains and inflammatory markers, controlling for age, sex, education, cardiovascular risk factors, obesity and other metabolic factors, smoking, alcohol consumption, depression and presence of the apolipoprotein
ε4
genotype. Regression analyses were repeated using four factors derived from a factor analysis of the cognitive tests. After Bonferroni correction for multiple testing, associations remained between raised levels of interleukin-12 and reduced performance in processing speed. Marked sex differences were noted in the abovementioned findings, with only females being significantly affected. Using the four factors derived from the factor analyses of cognitive test as dependent variables, interleukins-12 and -6 were both associated with the processing speed/executive function factor, even after controlling for relevant confounding factors. Thus, markers of systemic inflammation are related to cognitive deficits in a non-clinical community-dwelling elderly population, independent of depression, cardiovascular or metabolic risk factors, or presence of apolipoprotein ε4 genotype. Additional research is required to elucidate the pathophysiology and longitudinal development of these relationships.
Objectives
To compare the risk profiles of mild cognitive impairment (MCI) subtypes in a population‐based elderly sample.
Design
Cross‐sectional study.
Setting
The population‐based Sydney Memory and ...Ageing Study.
Participants
Seven hundred fifty‐seven English‐speaking, community‐dwelling individuals without dementia aged 70 to 90.
Measurements
Comprehensive neuropsychological assessments were used to diagnose MCI and its subtypes, categorized as amnestic (aMCI) or nonamnestic (naMCI) and as single‐ (sdMCI) or multiple‐ (mdMCI) domain. Risk profiles were derived from sociodemographic; lifestyle; and cardiac, physical, mental, and general health data. Whole‐sample and sex‐specific comparisons between aMCI and naMCI and between mdMCI and sdMCI were made using age‐ (and sex‐) adjusted multiple regressions comprising initially significant univariate factors.
Results
Risk factors for MCI were presence of the apolipoprotein E (APOE) ε4 allele, heart disease, high homocysteine, poor odor identification ability, low visual acuity, and lower mental activity. The odds of having naMCI rather than aMCI were lower with greater levels of social activity and greater if taking antihypertensives, the latter particularly in men. The odds of naMCI were greater in men taking antidepressants or with a longer 6‐meter walk time and in women with hypertension. The odds of having mdMCI rather than sdMCI were greater in participants with a history of depression or having the APOE ε4 allele. Greater odds of mdMCI were also associated with lower mental activity, particularly for women. For men, the odds of mdMCI were greater with the APOE ε4 allele and lower if diagnosed with high cholesterol.
Conclusion
MCI subtypes exhibit distinctive, sex‐dependent risk profiles. This is consistent with MCI subtypes having different etiologies and outcomes and supports the idea that subtyping MCI may offer predictive validity and clinical application.
Objectives
To examine whether impaired fasting glucose (IFG) represents an intermediary condition between normal fasting glucose and diabetes mellitus and, specifically, whether elderly adults with ...IFG have higher disease burden, cardiovascular risk, and systemic inflammation and higher 2‐year mortality and incident disease.
Design
Prospective observational study.
Setting
Population‐derived cohort.
Participants
Individuals with a mean age of 78.6 ± 4.7 (N = 945).
Measurements
Disease was ascertained using a standardized questionnaire at baseline and 2 years. Fasting metabolic, inflammatory, and oxidative metabolism markers were measured. Disease prevalence, cardiovascular risk, and biochemical markers were compared to determine disease burden and metabolic disturbances in IFG. Adjusted odds ratios (ORs) for 2‐year all‐cause mortality and incident disease were determined.
Results
IFG prevalence was 41%. Individuals with IFG had higher baseline rates of heart disease than those with normal fasting glucose (NFG), similar to that in individuals with diabetes mellitus. IFG was characterized by higher inflammatory markers and oxidative metabolism end products and was an intermediary between NFG and diabetes mellitus for triglycerides and malondialdehyde. Discriminant analysis showed that IFG was independently associated with stroke and higher triglycerides and oxidative stress. Two‐year all‐cause mortality was 3.9%. The 2‐year adjusted ORs for all‐cause mortality, incident cardiac disease, stroke, and cancer were similar between IFG and NFG, using both American Diabetes Association and World Health Organization IFG criteria. IFG did not predict secondary cardiac events, stroke, or cancer.
Conclusion
IFG was an intermediary condition for heart disease, inflammation, and oxidative stress in elderly adults but not for 2‐year incident disease or all‐cause mortality. Longer‐term prospective studies are needed to clarify whether IFG in elderly adults portends greater morbidity and mortality.
Objectives
To determine whether the metabolic syndrome (MetS) or its components were more closely associated with disease states and inflammation in elderly adults.
Design
Sydney Memory and Ageing ...Study. Cross‐sectional, observational cohort.
Setting
Population‐derived, community‐dwelling elderly adults.
Participants
Nine hundred thirty individuals aged 70 to 90.
Measurements
Age‐ and sex‐adjusted odds ratios (ORs) for disease states; fasting circulating inflammatory markers and oxidative metabolism byproducts.
Results
MetS was associated with diabetes mellitus (OR = 4.1, P < .001) and bowel cancer (OR = 9.1, P = .03) but not in analyses that controlled for component conditions. Models containing component conditions had the strongest associations with heart disease. Disease associations were improved after addition of component conditions to the MetS model. The reverse did not hold: disease associations were not improved when MetS was added to the components model. Low high‐density lipoprotein cholesterol (HDL‐C) was independently associated with myocardial infarction (OR = 2.32) and angina pectoris (OR = 2.59) (both P < .008). Waist circumference was independently associated with cancer (OR = 1.82, P = .008). Although MetS was associated with higher C‐reactive protein, vascular cell adhesion molecule, interleukin‐6, amyloid A, homocysteine, and malondialdehyde, it explained less than half of the variance of models containing its components.
Conclusion
The observation that MetS is associated with disease states and markers of circulating inflammation in the elderly is explained mainly by abdominal obesity and low HDL‐C. Longitudinal data will further clarify these cross‐sectional findings that MetS appears to be less than the sum of its parts in elderly adults.
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