Sex hormones, vascular factors and cognition.

After more than a century of research, we have failed to develop a pharmacological prevention or cure for dementia. There are strong indicators that sex hormones influence cognition. In this paper we discuss the role of these hormones at the intersection between vascular disease and dementia, in light of the mounting literature covering the shared risk factors, pathological features alongside the timeline of hormonal change with the evolution of vascular and neurodegenerative disease. Interactive risk factors and the role of inflammation over the duration of disease evolution are highlighted. Our summary tables assessing the impact of estrogen-based hormone therapy on cognition over the past 45 years illustrate the effort expended to determine the ideal age for intervention and the type, dose, administration, and duration of therapy that might improve or protect cognition as well as alleviate menopausal symptoms. As the prevalence of dementia is rising and is higher in women, it is crucial we advance our knowledge from the "inconclusive" position statement on menopausal hormone therapy of the US Preventive Services Task Force.

Association between Cognitive Function and Clustered Cardiovascular Risk of Metabolic Syndrome in Older Adults at Risk of Cognitive Decline.

OBJECTIVES: Metabolic syndrome (MetS) represents a cluster of obesity and insulin resistance-related comorbidities. Abdominal obesity, hypertension, elevated triglyceride and glucose levels are components of MetS and may have a negative effect on cognitive function, but few cognitive studies have examined the combined risk severity. We sought to determine which specific cognitive abilities were associated with MetS in older adults at risk of cognitive decline. DESIGN: Cross-sectional study. PARTICIPANTS: 108 AIBL Active participants with memory complaints and at least one cardiovascular risk factor. MEASUREMENTS: Cardiovascular parameters and blood tests were obtained to assess metabolic syndrome criteria. The factors of MetS were standardized to obtain continuous z-scores. A battery of neuropsychological tests was used to evaluate cognitive function. RESULTS: Higher MetS z-scores were associated with poorer global cognition using ADAS-cog (adjusted standardized beta=0.26, SE 0.11, p<0.05) and higher Trail Making B scores (adjusted beta=0.23, SE 0.11, p<0.05). Higher MetS risk was related to lower cognitive performance. CONCLUSION: Combined risk due to multiple risk factors in MetS was related to lower global cognitive performance and executive function. A higher MetS risk burden may point to opportunities for cognitive testing in older adults as individuals may experience cognitive changes.

Adherence to the Mediterranean Diet Is not Related to Beta-Amyloid Deposition: Data from the Women's Healthy Ageing Project.

BACKGROUND: Research has indicated the neuroprotective potential of the Mediterranean diet. Adherence to the Mediterranean diet has shown preventative potential for Alzheimer's disease incidence and prevalence, yet few studies have investigated the impact of Mediterranean diet adherence on the hallmark protein; beta-amyloid. OBJECTIVES: To investigate the association between Mediterranean diet adherence and beta-amyloid deposition in a cohort of healthy older Australian women. DESIGN: This study was a cross-sectional investigation of participants from the longitudinal, epidemiologically sourced Women's Healthy Ageing Project which is a follow-up of the Melbourne Women's Midlife Health Project. SETTING: Assessments were conducted at the Centre for Medical Research, Royal Melbourne Hospital in Melbourne, Australia. F-18 Florbetaben positron emission tomography scanning was conducted at the Austin Centre for PET in Victoria, Australia. PARTICIPANTS: One hundred and eleven Women's Healthy Ageing Project participants were included in the study. MEASUREMENTS: Mediterranean diet adherence scores for all participants were calculated from the administration of a validated food frequency questionnaire constructed by the Cancer Council of Victoria. Beta-amyloid deposition was measured using positron emission tomography standardised uptake value ratios. RESULTS: Gamma regression analysis displayed no association between Mediterranean diet adherence and beta-amyloid deposition. This result was consistent across APOE-ε4 +/- cohorts and with the inclusion of covariates such as age, education, body mass index and cognition. CONCLUSIONS: This study found no association between adherence to the Mediterranean diet and beta-amyloid deposition in a cohort of healthy Australian women.

A comparison of Geriatric Depression Scale scores in older Australian and Japanese women.

AIMS: The aim of this study was to compare the prevalence of depressive symptoms in Australian and Japanese populations of community-dwelling older women using the Geriatric Depression Scale (GDS-15). In addition, the relationship between lifestyle and health factors and higher ratings of depressive symptoms was also examined to determine if there were culturally consistent risk factors associated with higher depressive symptom scores. METHODS: A total of 444 community based women aged between 65 and 77 years completed a depressive symptom measure (GDS-15) and provided information on common lifestyle factors. The Australian sample (n = 222) were drawn from the Women's Healthy Ageing Project and the age-matched, Japanese sample from the Kumamoto Ageing Study of Mental Health (n = 222). The GDS was chosen to; (1) reduce the impact of physical symptoms associated with old age and, (2) reduce the inflation in scores that may result from the Japanese tendency to endorse somatic items more often than Western adults. RESULTS: Mean GDS total scores were significantly higher for the Japanese population 3.97 ± 3.69 compared with 1.73 ± 2.7 for Australian women. The percentages of women scoring in the normal; mild and moderate ranges for depression were 91, 7 and 2% for Australia and 67, 24 and 9% for Japan. Scores remained significantly higher for the Japanese cohort when controlling for lifestyle and health factors associated with depression. The analysis of lifestyle and health characteristics showed that the greatest difference between cohorts was in the area of living status, with more Australian women living with their partner and more than three times as many Japanese women living with their children. When the data for the countries was considered independently employment status affected the likelihood of higher depression scores in the Australian sample while heart disease and poor sleep impacted the risk for the Japanese population. CONCLUSIONS: Significantly more Japanese women scored within the mild and moderate ranges on the GDS compared with their Australian peers, even when controlling for possible confounding factors. Of the lifestyle and health factors assessed in this analysis no single variable was a common risk factor for higher depressive scores for both countries. The presence of cultural influences that may impact the risk of experiencing depressive symptoms, and culture specific patterns of item endorsement on depressive symptom measures, needs to be explored in more detail.

Dietary patterns and cognitive decline in an Australian study of ageing.

The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.

Associations between gonadotropins, testosterone and ß amyloid in men at risk of Alzheimer's disease.

Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of ß amyloid (Aß) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aß levels have focused primarily on plasma Aß(1-40) and not on the more pathogenic Aß(1-42). Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma Aß levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman's rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma Aß(1-40) and Aß(1-42) levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aß(1-40); beta=0.208, P=0.017; Aß(1-42); beta=0.215, P=0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups. In SMC, increased frequency of the APOE-ɛ4 allele (beta=0.536, P<0.001) and increasing serum LH levels (beta=0.421, P=0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-ɛ4 allele copy number (beta=0.674, P<0.001) and decreasing calculated free testosterone (beta=-0.303, P=0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease.

Factors affecting subjective memory complaints in the AIBL aging study: biomarkers, memory, affect, and age.

BACKGROUND: The prognostic value of subjective memory complaints (SMCs) in the diagnosis of dementia of the Alzheimer's type is unclear. While some studies have found an association between SMCs and cognitive decline, many have found a stronger association with depression, which raises questions about their diagnostic utility. METHODS: We examined the cross-sectional association between SMC severity (as measured using the MAC-Q, a brief SMC questionnaire) and affect, memory, and Alzheimer's disease (AD) biomarkers (ß-amyloid deposition and the apolipoprotein E ε4 (APOEε4) allele) in healthy elderly controls (HC; M = 78.74 years, SD = 6.7) and individuals with mild cognitive impairment (MCI; M = 72.74 years, SD = 8.8). We analyzed a subset of individuals drawn from the Australian Imaging Biomarkers and Lifestyle (AIBL) Study of Aging. RESULTS: SMCs were more severe in MCI patients than in HCs. SMC severity was related to affective variables and the interaction between age and group membership (HC/MCI). Within the HC group, SMC severity was related to affective variables only, while severity correlated only with age in the MCI group. SMCs were not related to cognitive variables or AD biomarkers. CONCLUSION: SMCs were related to solely by poorer mood (greater depressive and anxious symptomatology) in the cognitively healthy elderly however mean levels were subclinical. This finding argues for the assessment of affective symptomatology in conjunction with cognitive assessment in elderly memory complainers. Future AIBL research will focus on assessing other AD biomarkers, such as brain atrophy and Aß plasma markers, in relation to complaint severity. Once our 36-month follow-up data are collected, we propose to assess whether SMCs can predict future cognitive decline.

Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease.

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes and degeneration have previously been reported in AD using optical coherence tomography and laser Doppler techniques. This report presents results from analysis of retinal photographs from AD and healthy control participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. This is the first study to investigate retinal blood vessel changes with respect to amyloid plaque burden in the brain. We demonstrate relationships between retinal vascular parameters, neocortical brain amyloid plaque burden and AD. A number of RVPs were found to be different in AD. Two of these RVPs, venular branching asymmetry factor and arteriolar length-to-diameter ratio, were also higher in healthy individuals with high plaque burden (P = 0.01 and P = 0.02 respectively, after false discovery rate adjustment). Retinal photographic analysis shows potential as an adjunct for early detection of AD or monitoring of AD-progression or response to treatments.

Physical activity and amyloid-ß plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing.

Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-ß (Aß) and Aß brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aß and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ε4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aß levels were measured in fasting blood samples. A subgroup (n=116) underwent (11)C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aß1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aß from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aß1-42/1-40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.

Intense physical activity is associated with cognitive performance in the elderly.

Numerous studies have reported positive impacts of physical activity on cognitive function. However, the majority of these studies have utilised physical activity questionnaires or surveys, thus results may have been influenced by reporting biases. Through the objective measurement of routine levels of physical activity via actigraphy, we report a significant association between intensity, but not volume, of physical activity and cognitive functioning. A cohort of 217 participants (aged 60-89 years) wore an actigraphy unit for 7 consecutive days and underwent comprehensive neuropsychological assessment. The cohort was stratified into tertiles based on physical activity intensity. Compared with individuals in the lowest tertile of physical activity intensity, those in the highest tertile scored 9%, 9%, 6% and 21% higher on the digit span, digit symbol, Rey Complex Figure Test (RCFT) copy and Rey Figure Test 30-min recall test, respectively. Statistically, participants in the highest tertile of physical activity intensity performed significantly better on the following cognitive tasks: digit symbol, RCFT copy and verbal fluency test (all P<0.05). The results indicate that intensity rather than quantity of physical activity may be more important in the association between physical activity and cognitive function.

Adherence to a Mediterranean diet and Alzheimer's disease risk in an Australian population.

The Mediterranean diet (MeDi), due to its correlation with a low morbidity and mortality for many chronic diseases, has been widely recognised as a healthy eating model. We aimed to investigate, in a cross-sectional study, the association between adherence to a MeDi and risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large, elderly, Australian cohort. Subjects in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing cohort (723 healthy controls (HC), 98 MCI and 149 AD participants) completed the Cancer Council of Victoria Food Frequency Questionnaire. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD and MCI status in multinominal logistic regression models that were adjusted for cohort age, sex, country of birth, education, apolipoprotein E genotype, total caloric intake, current smoking status, body mass index, history of diabetes, hypertension, angina, heart attack and stroke. There was a significant difference in adherence to the MeDi between HC and AD subjects (P < 0.001), and in adherence between HC and MCI subjects (P < 0.05). MeDi is associated with change in Mini-Mental State Examination score over an 18-month time period (P < 0.05) in HCs. We conclude that in this Australian cohort, AD and MCI participants had a lower adherence to the MeDi than HC participants.

Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging.

OBJECTIVE: There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which included both healthy controls and participants with early-stage AD. METHODS: Total apoE and apoE4 were measured in 1,079 individuals drawn from the highly characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Total and isoform-specific plasma apoE levels were then compared with cerebral Aß load, as assessed by PET using Pittsburgh compound B (PiB). RESULTS: Total apoE and apoE4 levels were found to be significantly lower in patients with AD in the entire cohort, and decrease with Aß load in the PiB-PET subset. ApoE levels were significantly lower among ε4 homozygous individuals. In APOE ε3/ε4 heterozygote carriers, apoE4 levels decrease, indicating that apoE3 levels increase with disease. CONCLUSION: Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level. The significance of these findings will be determined in the AIBL longitudinal study of aging.

Neuropsychiatric symptomatology predicts seizure recurrence in newly treated patients.

OBJECTIVES: To test the hypothesis that neuropsychiatric symptomatology is predictive of the success of seizure control in patients newly treated with antiepileptic drugs (AEDs), and that this predictive value adds to that provided by other clinical, imaging, and genomic factors in a multivariate model. METHODS: One hundred seventy newly treated patients with epilepsy completed the A-B Neuropsychological Assessment Scale (ABNAS) before commencing AED therapy and were prospectively followed up for 12 months. Patients were classified as nonresponsive if they had at least 1 seizure not explained by medication noncompliance or other significant provoking factors. RESULTS: Of the 138 patients in whom a drug response phenotype at 12 months was able to be determined, nonresponsive patients (n = 45) had a higher pretreatment ABNAS score than patients whose seizures were controlled (n = 93) (p = 0.007). A lesion on MRI was also associated with a higher risk of seizure recurrence (p = 0.003). On multivariate logistic regression, the ABNAS score, the MRI results, and a genomic classifier were all independently predictive of treatment outcome. For AED pharmacoresponse, this multivariate model had diagnostic values of 91% sensitivity, 64% specificity, 84% positive predictive, and 78% negative predictive values. The predictive value of the ABNAS score was validated in a second prospective cohort of 74 newly treated patients with epilepsy (p = 0.005). CONCLUSIONS: The ABNAS provides prognostic information regarding successful seizure control in patients newly treated with AEDs. Furthermore, these results demonstrate the multifactorial nature of the determinants of AED response, with neuropsychological, structural, and genomic factors all contributing to the complex response phenotype.

Beta-amyloid burden in the temporal neocortex is related to hippocampal atrophy in elderly subjects without dementia.

OBJECTIVE: To investigate whether global and regional beta-amyloid (Abeta) burden as measured with 11C Pittsburgh compound B (PIB) PET is associated with hippocampal atrophy characterized using MRI in healthy controls and patients with amnestic mild cognitive impairment (aMCI) or Alzheimer disease (AD). METHODS: Ninety-two elderly healthy controls, 32 subjects with aMCI, and 35 patients with AD were imaged using 11C-PIB PET and MRI. Hippocampal volume was measured and PIB standardized uptake value ratio was extracted after partial volume correction within 41 regions of interest. Global, regional, and voxel-based correlations between PIB and hippocampal volume were computed for each group. RESULTS: In healthy control participants with elevated neocortex PIB retention, significant correlation was found between PIB retention in the inferior temporal region and hippocampal volume using both region-based and voxel-based approaches. No correlation was found in any other group. CONCLUSIONS: The strong correlation between hippocampal atrophy and beta-amyloid (Abeta) burden in the Pittsburgh compound B-positive healthy control group suggests that Abeta deposition in the inferior temporal neocortex is related to hippocampal synaptic and neuronal degeneration.

Physician diagnosed arthritis, reported arthritis and radiological non-axial osteoarthritis.

OBJECTIVE: To determine the question that best predicts radiographic evidence of non-axial osteoarthritis (OA). DESIGN: The Melbourne Women's Mid-life Health Project (MWMHP), commenced in 1991, is a population-based prospective study of 438 Australian-born. Two hundred and fifty-seven (57%) women remained in longitudinal assessment in 2002 and 224 (87%) women agreed to undergo X-rays of their hands and knees between 2002 and 2003. METHODS: Annually participants were asked about aches and stiff joints and arthritis or rheumatism. In the eleventh year of follow-up X-rays were scored for evidence of OA using a validated scale, by two investigators who were blinded to questionnaire results. Information on hormone therapy use, physical activity, mood, smoking, body mass index (BMI) and age were obtained by both self-administered and face-to-face questionnaires. RESULTS: Patient reported physician diagnosed arthritis was the best predictor of radiological OA (ROA). The question had a specificity of 64%, a positive predictive value of 57% and a negative predictive value of 71%. Even the most reliable question about arthritis still had a relatively low specificity for radiologically diagnosed OA. Reporting symptoms were significantly more common in participants who were depressed, those who had a higher negative affect and those with a higher BMI. CONCLUSION: In large epidemiological studies where questionnaire assessment of OA is required, the greatest accuracy is achieved by asking about physician diagnosed arthritis. Concurrent application of a validated scale for mood is important.

The relationship of reports of aches and joint pains to the menopausal transition: a longitudinal study.

UNLABELLED: OBJECTIVES Part I: To determine factors associated with reported joint symptoms across the menopausal transition. Part II: To investigate the relationship between symptom reporting and radiological arthritis in postmenopausal women. DESIGN Part I: The Melbourne Women's Mid-life Health Project, commenced in 1991, is a population-based prospective study of 438 Australian-born women, aged 45-55 years and menstruating at baseline; they were interviewed annually over 8 years. The retention rate was 88% (n = 387). Part II: After 12 years of follow-up, 257 (57%) women returned for assessment and 224 agreed to undergo X-rays of their hands and knees. METHODS Part I: Annual fasting blood collection, physical measurements, and interviews including questions about bothersome aches or stiff joints in the previous 2 weeks. A score for this symptom was calculated from the product of the severity and frequency data. These data were analyzed using random-effects time-series regression models. Part II: X-rays were scored for evidence of osteoarthritis using a validated scale, by two investigators who were blinded to questionnaire results. RESULTS Part I: 'Aches and stiff joints' were the most commonly reported symptom and reporting increased over time in the longitudinal study. Variables significantly associated with reporting bothersome aches and stiff joints were high body mass index (BMI) (p < 0.001), high negative mood (p < 0.01), not being employed (p < 0.001), and experiencing the menopausal transition (p < 0.05). A higher severity and frequency of this symptom were associated with BMI (p < 0.01), not being employed (p < 0.05) and high negative mood (p < 0.005). Part II: The relationship between radiological osteoarthritis and symptom reports approached statistical significance (p = 0.06). Knee osteoarthritis was significantly associated with symptom reports (p = 0.008) but not hand osteoarthritis (p = 0.2). CONCLUSION: Menopausal status, BMI, employment status and depressed mood were all associated with the experience of bothersome aches and stiff joints. Aches and stiff joints, common in postmenopausal women, are not necessarily indicative of radiological osteoarthritis.

Factors affecting the prevalence of osteoarthritis in healthy middle-aged women: data from the longitudinal Melbourne Women's Midlife Health Project.

The prevalence of osteoarthritis (OA) is greater in women then men. Weight, a factor strongly associated with osteoarthritis, is significantly increased over the menopausal transition. Despite the high prevalence of osteoarthritis, a disabling disease with limited treatment options, there is a paucity of studies in women. The longitudinal phase of the Melbourne Women's Midlife Health Project, is a population-based prospective study of 438 Australian born women who have been followed annually over 11 years. 257 (59%) of these women remained in longitudinal assessment at 11th year of follow-up and 224 of these women agreed to undergo X-rays of their knees and hands. In this study, X-rays were scored for evidence of osteoarthritis using a validated scale, by two investigators who were blinded to questionnaire results. Information on hormone therapy use, physical activity, smoking, BMI and age were obtained by both self-administered and face-to-face questionnaires. Results showed that one hundred and twenty-eight women (56%) had evidence of radiological OA. Forty-nine (21.6%) had evidence of radiological knee OA. One hundred and one (44.5%) had evidence of radiological hand OA. Compared to baseline, at 11th year of follow-up participants had put on weight (4 kg range -14 to 25 kg) and a larger proportion (25% vs. 40%) reported exercising frequently (P = 0.005). Physical activity and BMI were associated with higher prevalence of osteoarthritis in the final year of follow-up. Smoking was associated with a lower prevalence of radiological knee OA. The prevalence was 61% among never smokers compared to only 39% among those who smoked (P < 0.05). Total OA was associated with never having used hormone therapy (odds ratio 2.7; CI 1.1-6.9). There was a trend for increasing level of physical activity at ages 20-29 to be associated with an increased risk of knee OA (P value 0.03 for trend). In conclusion increasing age, BMI and history of more frequent physical activity in younger years were risk factors for radiological knee OA. In contrast, smoking appeared to be associated with less knee OA. Never having used hormone therapy was a risk factor for radiological hand and knee OA. Further work will be needed to determine whether modification of these factors can prevent the development of OA.

Self-reported arthritis and the menopause.

OBJECTIVES: To determine the prevalence of self-reported arthritis in a population-based cohort of mid-aged women and to identify health, social and lifestyle factors associated with self-reported arthritis. DESIGN: Cross-sectional population-based survey. METHOD: Data were obtained from a telephone-administered questionnaire of 2001 Australian-born women between 45 and 55 years old and residing in Melbourne. Information was collected on demographics, lifestyle factors and health conditions. RESULTS: The most commonly reported symptom in this cohort was aches and stiff joints, reported by 51.7% of the women; 34.4% of participants reported they had been diagnosed with arthritis. More postmenopausal women (39%) reported that they were diagnosed with arthritis compared to premenopausal women (27%, p < 0.001). Women who reported arthritis were more likely to be older (odds radio (OR), 1.09; 95% confidence interval (CI), 1.05-1.13), have a higher body mass index (OR, 1.04; CI, 1.02-1.07), be postmenopausal (OR, 1.88; CI, 1.33-2.66), have a higher negative mood (OR, 1.80; CI, 1.13-2.87), and report a decreased interest in sex (OR, 1.58; CI, 1.26-1.97). CONCLUSIONS: Aches and stiff joints are the most frequently reported symptom of mid-aged women. Reported arthritis is associated with postmenopausal status, age, body mass index, less interest in sex and lowered mood. Further longitudinal research is needed to determine the role of these factors in the development and impact of arthritis.

Serial MRI in multiple sclerosis: a prospective pilot study of lesion load, whole brain volume and thalamic atrophy.

Using serial magnetic resonance imaging (MRI), we investigated the relationship between diffuse cerebral atrophy, T1 and T2 lesion volumes, mean thalamic volumes and clinical progression in patients with established multiple sclerosis (MS). Eleven patients were included in this prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, and T2 hyperintense lesion volumes at baseline and at up to 3 years follow-up were assessed on MRI brain scans. As a putative measure of cerebral atrophy mean thalamic volumes were also obtained. The outcome measures were the MRI parameters and disability on Kurtzke's expanded disability status scale (EDSS). Of the 11 patients 6 worsened clinically as measured by an increase of 0.5 or more on the EDSS. Cerebral atrophy occurred in 91% of patients and was independent of changes in lesion volumes and was not associated with disease progression as determined by the EDSS.