Cardiovascular risk factors and life events as antecedents of depressive symptoms in middle and early-old age: The Path Through Life Study. Anstey, K. J., Burns, R., Butterworth, P., Windsor, T. D., Christensen, H., & Sachdev, P. (2009). Psychosomatic Medicine. 71: 937-943

Objective: To evaluate cardiovascular risk factors (CVRF) and life events (LE) as predictors of depressive symptoms in a mid-life and an early late-life cohort to determine whether they had independent or interacting effects, and whether there were age differences in the effects.

Methods: Cohorts aged 40 to 44 years (n = 2530) and 60 to 64 years (n = 2551) at baseline (Wave 1) were followed up after four years (Wave 2) as part of the PATH Through Life project based in Canberra and Queanbeyan, Australia. Cross sectional analyses evaluated rates of CVRF and LE in depressed compared with nondepressed participants. Hierarchical generalized linear models were used to evaluate demographic variables, CVRF (diabetes, smoking, alcohol, body mass index, cholesterol medication, hypertension), LE, and Wave 1 depressive symptoms as predictors of depressive symptoms at Wave 2.

Results: At baseline, those with high levels of depressive symptoms were more likely to report smoking, using cholesterol-lowering medications, hypertension, diabetes, past stroke, and higher body mass index. Predictors of depressive symptoms at Wave 2 in the cohort of 40-44 year old persons included Wave 1 depressive symptoms, diabetes, and LE at Wave 2. In the cohort of 60-64 year old individuals, Wave 1 depression, stroke, smoking, low education, and Wave 2 LE predicted depressive symptoms. There was no evidence of interactions between CVRF and LE.

Conclusions: LE and CVRF are independent sets of risk factors for depressive symptoms with different effects in the 40-44 year old and 60-64 year old cohorts. These findings have implications for preventative strategies for depression.

Cognitive Deficits Are Associated with Frontal and Temporal Lobe White Matter Lesions in Middle-Aged Adults Living in the Community  Bunce, D., Anstey,K.J., Cherbuin, N., Burns, R., Christensen, H., Wen, W., & Sachdev, P. (2010 PLOS ONE 5 (10) Article Number: e13567

Background: The association between brain white matter lesions and cognitive impairment in old age is well established. However, little is known about this association in midlife. As this information will inform policy for early preventative healthcare initiatives, we investigated non-periventricular frontal, temporal, parietal and occipital lobe white matter hyperintensities (WMH) in relation to cognitive function in 428 (232 women) community dwelling adults aged 44 to 48 years.

Results: Frontal white matter lesions were significantly associated with greater intraindividual RT variability in women, while temporal WMH were associated with face recognition deficits in men. Parietal and occipital lobe lesions were unrelated to cognitive performance. These findings did not differ when education and a range of health variables, including vascular risk factors, were taken into account.

Conclusion: Gender differences in WMH cognition associations are discussed, and we conclude that small vessel disease is present in midlife and has functional consequences which are generally not recognized. Preventative strategies should, therefore, begin early in life.

Subjective wellbeing mediates the effects of resilience and mastery on depression and anxiety in a large community sample of young and middle-aged adults Burns, R.A. Anstey, K.J, Windsor TD (2010) Australian and New Zealand Journal of Psychiatry 2010; Early Online, 1 – 9

Objectives: The tripartite model of depression and anxiety hypothesizes that positive and negative affect is related to depression and anxiety. However, the specific role of cognitive or psychological well-being constructs like resilience and mastery within a tripartite context and throughout adulthood is unclear.

Method: Data was drawn from two longitudinal population-based cohorts, aged 20-24 and 40-44 based in Canberra, Australia (N = 3989). We sought to determine the interrelatedness of two affective measures of subjective wellbeing, positive and negative affect, with two cognitive measures of psychological wellbeing, resilience and mastery. We then tested their independent effects on depression and anxiety, and hypothesized, following the tripartite model, that subjective wellbeing would mediate the effects of the psychological wellbeing variables on mental health and that the psychological wellbeing variables would be more strongly related to positive subjective wellbeing.

Results: Principal axis factoring delineated four affective and cognitive dimensions of wellbeing comprising positive and negative affect, resilience and mastery. Structural equation models identified the psychological wellbeing variables as significantly related to subjective wellbeing, which fully mediated the effects of resilience and partially mediated the effect of mastery on depression and anxiety. These findings were consistent throughout both young and middle adulthood.

Conclusion: Psychological wellbeing components are significant predictors of subjective wellbeing affect states that increase vulnerability to depression and anxiety.

Factors that explain the poorer mental health of caregivers: results from a community survey of older Australians Butterworth P, C. Pymont, B. Rodgers, T. D. Windsor &  K.J. Anstey. (2010). .  Australian and New Zealand Journal of Psychiatry 44 (7), 616-624

Objectives: To contrast the level of anxiety and depression reported by older Australians providing assistance to someone who is ill, disabled or elderly with that of non-caregivers; and to identify secondary stressors and mediating factors which explain caregivers' poorer mental health.

Method: Analysis of data from wave 2 of the PATH Through Life Study, a community survey of 2,222 adults aged 64-69 years conducted in Canberra and Queanbeyan, Australia. Mental health was assessed using the Goldberg depression and anxiety scales. Analyses focused on those who identified themselves as a primary carer and/or reported providing care for more than five hours per week. Analyses evaluated whether the association between caregiver status and mental health was mediated by financial factors, role strain, physical health, and social support and conflict with family and friends after adjusting for demographics.

Results: Caregivers reported significantly poorer mental health than non-caregivers, and also reported poorer physical health, greater financial stress, greater responsibility for household tasks, and more conflict and less social support from their family and spouse. Mediation analysis showed that the poorer mental health of caregivers reflected elevated rates of their own physical impairment, a lack of social support and greater conflict.

Conclusions: The relationship between caregiving and mental health was largely explained by social support and levels of conflict within the family, which are modifiable and potentially amenable to change through policy and intervention. Research such as this can assist the development of appropriate interventions to improve the circumstances of informal caregivers in Australia.

Mixed handedness is associated with greater age-related decline in volumes of the hippocampus and amygdala: the PATH through life study.  Cherbuin N, Sachdev P, Anstey K (2011). Brain and Behavior doi: 10.1002/brb3.24

Handedness has been found to be associated with structural and functional cerebral differences. Left handedness and mixed handedness also appear to be associated with an elevated risk of some developmental and immunological disorders that may contribute to pathological processes developing in ageing. Inconsistent reports show that left handedness may be more prevalent in early onset as well as late onset Alzheimer’s disease, but might also be associated with slower decline. Such inconsistencies may be due to handedness being usually modeled as a binary construct while substantial evidence suggests it to be a continuous trait. The aim of this study was to investigate the relationship between brain structures known to be implicated in pathological ageing and strength and direction of handedness. The association between handedness and hippocampal and amygdalar atrophy was investigated in 327 cognitively healthy older individuals.Handedness wasmeasured with the Edinburgh Inventory. Two measures were computed from this index, one reflecting the direction (left = 0/right = 1) and the other the degree of handedness  (ranging from 0 to 1). Hippocampal and amygdalar volumes were manually traced on scans acquired 4 years apart. Regression analyses were used to assess the relationship between strength and direction of handedness and incident hippocampal and amygdalar atrophy. Analyses showed that strength but not direction of handedness was a significant predictor of hippocampal (Left: beta = 0.118, P = 0.013; Right:  beta = 0.116, P = 0.010) and amygdalar (Right: beta = 0.105, P = 0.040) atrophy.  The present findings suggest that mixed but not left handedness is associated with greater hippocampal and amygdalar atrophy. This effect may be due to genetic,  environmental, or behavioural differences that will need further investigation in future studies. Cognitive performance and health behaviours. This paper examined the association between cognitive ability and health behaviours over time. It was found that those who performed better in the cognitive testing had higher levels of precautionary health behaviour such as taking vitamins and minerals and physical activity. However, the greatest improvement in health behaviours over four years was seen in those who performed more poorly in the Wave 1 cognitive testing. This suggests that other factors such as increasing health education, greater affluence or more available health education may influence improved health behaviours, particularly in those with lower cognitive scores.

Neuropsychological predictors of transition from healthy cognitive aging to mild cognitive impairment: The PATH Through Life Study.  Cherbuin, N., Sachdev, P. & Anstey, K. J. (2010). American Journal of Geriatric Psychiatry, 18(8), 723-33.

Objective: To identify neuropsychological predictors of transition from healthy cognitive aging to mild cognitive impairment (MCI) or any mild cognitive disorder (any MCD) in a community based longitudinal study of aging.

Design: Longitudinal Participants: Two thousand eighty-two individuals, aged 60-64 years and participating in a prospective epidemiologic study of mental health, and aging were assessed at two time points 4 years apart for MCI using the International Consensus Criteria, the clinical dementia rating scale (CDR, 0.5), or any of a suite of criteria sets for MCDs (any-MCD).

Measurements: Logistic regression was used to assess the neuropsychological predictors of conversion to diagnosis including the Mini-Mental State Examination, immediate and delayed recall (IR and DR), Digit Backward, Spot-the-Word (STW), Symbol Digits Modalities Test ( SDMT), simple and choice reaction time, and reaction time variability.

Results: Of the 2,082 participants with no cognitive impairment in the first wave of data collection, 18 participants were diagnosed with MCI, 32 with CDR 0.5, and 64 participants presented with any MCD four years later. The main neuropsychological predictors of conversion identified in multivariate analyses were measures of IR/DR, STW, Symbol Digit Modalities Task, and reaction time variability.

Conclusions: Although most measures were significant predictors of conversion to MCI or any MCD when assessed independently, four tests (IR/DR, STW, SDMT, and simple reaction time variability) accounted for the explained variance in diagnosis when all tests were assessed together. When predictive value, stability across clinical categories, and psychometric characteristics were considered together, the reaction time variability measure was the best predictor of future cognitive disorder.

Lifetime cigarette smoking is associated with striatal volume measures. Das D, Cherbuin N, Anstey KJ, Sachdev PS, Easteal S (2011) Addiction Biology doi:10.1111/j.1369-1600.2010.00301.x

Nicotine, the primary addictive component of tobacco, affects the mammalian brain. Smokers’ brains have smaller cortical grey matter volumes and/or lower densities compared with non-smokers’. Differences in subcortical structures like the striatum are however, less clear. A high concentration of nicotinic receptors makes the striatum a potential target for nicotine. In addition, striatal nuclei are essential components of the reward/reinforcement pathway involved in addiction. The aim of this study was to explore the relationship between striatal nuclei (caudate, putamen and nucleus accumbens area) volumes and lifetime smoking in a large community-based sample of ‘young–old’ individuals. Brain volumes were measured using a semi-automated method in 315 participants aged 64–70 years who were selected from a larger randomly sampled cohort and who consented to a magnetic resonance imaging scan. Multiple regression analysis was used to assess the relationship between striatal volumes and cigarette smoking measures while controlling for age, sex, intracranial and total brain volumes and general physical and mental health measures. Greater lifetime use of cigarettes (measured in pack-years) was associated with smaller left nucleus accumbens area volume (P = 0.018) and larger left putamen volume (P = 0.025). Greater putaminal volume was also associated with a lower age at smoking initiation (P = 0.004). In this generally healthy cohort, lifetime use of cigarettes is significantly associated with striatal volume measures. These changes could indicate predisposing factors for nicotine addiction, or an effect of chronic nicotine exposure or a combination of both.

Baseline factors predictive of serious suicidality at follow-up: findings focussing on age and gender from a community-based study.  Fairweather-Schmidt, K. Anstey, K.J. Salim A. Rodgers B (2010) BMC Psychiatry, 10:41

Background: Although often providing more reliable and informative findings relative to other study designs, longitudinal investigations of prevalence and predictors of suicidal behaviour remain uncommon. This paper compares 12 month prevalence rates for suicidal ideation and suicide attempt at baseline and follow up; identifies new cases and remissions; and assesses the capacity of baseline data to predict serious suicidality at follow up, focusing on age and gender differences.

Methods: 6,666 participants aged 20-29, 40-49 and 60-69 years were drawn from the first (1999-2001) and second (2003-2006) waves of a general population survey. Analyses involved multivariate logistic regression.

Results: At follow up, prevalence of suicidal ideation and suicide attempt had decreased (8.2%-6.1%, and 0.8%-0.5%, respectively). However, over one quarter of those reporting serious suicidality at baseline still experienced it four years later. Females aged 20-29 never married or diagnosed with a physical illness at follow up were at greater risk of serious suicidality (OR = 4.17, 95% CI = 3.11-5.23; OR = 3.18, 95% CI = 2.09-4.26, respectively). Males aged 40-49 not in the labour force had increased odds of serious suicidality (OR = 4.08, 95% CI = 1.6-6.48) compared to their equivalently-aged and employed counterparts. Depressed/anxious females aged 60-69 were nearly 30% more likely to be seriously suicidal.

Conclusions: There are age and gender differentials in the risk factors for suicidality. Life circumstances contribute substantially to the onset of serious suicidality, in addition to symptoms of depression and anxiety. These findings are particularly pertinent to the development of effective population based suicide prevention strategies.

Cognitive functions in middle aged and older adults: relationships with frontal grey matter volumes and thickness from the PATH through life study.  Gautam P, Cherbuin N, Sachdev S, Wen W, Anstey KJ (2011) Neuroimage 2011 (published online 19 January – doi: 10.1016/j.neuroimage.2001.01.015 – PMID: 21255657)

The study examined the relationship of lateral frontal cortical volume and thickness with cognitive function in two samples of healthy middle aged (MA, 44-48 years old) and early old-age (OA, 64-68 years old) adults. T1-weighted magnetic resonance imaging scans were acquired in 400 MA and 397 OA adults from respective random community samples. Cortical volumes and thickness were measured with a surface-based segmentation procedure (http://surfer.nmr.mgh.harvard.edu). Volumes of lateral frontal grey matter were found to be significantly lower for OA than MA. Structure-function relationships were investigated using path analyses. In OA, smaller lateral frontal volumes were associated with better episodic memory (EM) (p < 0.012, B = - 0.117), and Symbol-Digit Modalities Test (SDM) (p < 0.031, B = - 0.118) performance. Smaller frontal cortical thickness was also associated with better EM (p < 0.01) and SDM (p < 0.01) performance in OA. However, in MA greater cortical thickness was associated with better EM and (p < 0.01) and reaction time (RT) (p < 0.01). OA cohort showed significant positive correlations between Total Brain Volume and SDM, Digit-Backwards span and RT. Possible explanations and implications of the relationships in the context of cognitive aging in healthy adults, and limitations of cross-sectional research are discussed.

Are ecstasy users biased toward endorsing somatic mental health symptoms? Results from a general community sample.  George A, Windsor TD, Rodgers B (2010) Psychopharmacology. December online DOI 10.1007/s00213-010-2100-8

Rationale: Whether the reported poorer mental health of ecstasy users is due to a bias in endorsement of somatic symptoms has been postulated, but rarely examined.

Objectives: The purpose of this study is to investigate whether levels of ecstasy use were associated with differential probabilities of endorsing somatic mental health symptoms.

Methods: Current ecstasy users aged 24-30 years (n = 316) were identified from a population-based Australian study. Measures included frequency of ecstasy, meth/amphetamine, and cannabis use and the Goldberg anxiety/depression symptom scales.

Results: Multiple indicator, multiple cause models demonstrated no bias towards endorsing somatic symptoms with higher ecstasy use, both with and without adjustment for gender, cannabis, and meth/amphetamine use.

Conclusions: Other studies using alternate measures of mental health should adopt this approach to determine if there is a bias in the endorsement of somatic symptoms among ecstasy users.

The limitations of employment as a tool for social inclusion.  Leach, L.S., Butterworth, P., Strazdins, L., Rodgers, B., Broom, D. H & Olesen, S.  (2010). BMC Public Health. 10:621 (19 October 2010)

Background:  One important component of social inclusion is the improvement of well-being through encouraging participation in employment and work life. However, the ways that employment contributes to wellbeing are complex. This study investigates how poor health status might act as a barrier to gaining good quality work, and how good quality work is an important pre-requisite for positive health outcomes.

Methods: This study uses data from the PATH Through Life Project, analysing baseline and follow-up data on employment status, psychosocial job quality, and mental and physical health status from 4261 people in the Canberra and Queanbeyan region of south-eastern Australia. Longitudinal analyses conducted across the two time points investigated patterns of change in employment circumstances and associated changes in physical and mental health status.

Results: Those who were unemployed and those in poor quality jobs (characterised by insecurity, low marketability and job strain) were more likely to remain in these circumstances than to move to better working conditions. Poor quality jobs were associated with poorer physical and mental health status than better quality work, with the health of those in the poorest quality jobs comparable to that of the unemployed. For those who were unemployed at baseline, pre-existing health status predicted employment transition. Those respondents who moved from unemployment into poor quality work experienced an increase in depressive symptoms compared to those who moved into good quality work. Conclusions: This evidence underlines the difficulty of moving from unemployment into good quality work and highlights the need for social inclusion policies to consider people's pre-existing health conditions and promote job quality.

Could better jobs improve mental health? A prospective study of change in work conditions and mental health in mid-age adults.  Strazdins, L., D’Souza, R.M., Clements, M., Broom, D H,  Rodgers, B.,  & Berry H. (2010) Journal of Epidemiology and Community Health. 2009.093732Published Online First: 1 June 2010 doi:10.1136/jech.2009.093732

Objectives: To investigate the extent improvement or deterioration in employee job security, control or workload is associated with a change in mental health.

Design: Self report panel data (2000, 2004) on mental health (symptoms of depression and generalised anxiety) and job demands, control and insecurity. Changes in exposures and outcomes were calculated by subtracting wave 1 from wave 2 scores. Changes in mental health were regressed onto changes in work conditions, adjusting for confounders. Sensitivity analyses assessed reverse causation, floor and ceiling effects.

Setting: Two adjoining cities in south east Australia.

Participants: 1975 employees aged 40–48 years, 50% (n=995) male.

Results: Improvements and deterioration in each work condition were associated with corresponding improvements or deterioration in mental health. The association between changes in job insecurity and symptoms of depression was B=0.386 (95% CI 0.245 to 0.527) and with anxiety symptoms was B=0.434 (95% CI 0.267 to 0.601). Similarly, changes in job control were associated with changes in depressive (B=−0.548; 95% CI −0.791 to −0.304) and anxiety symptoms (B=−0.608; 95% CI −0.896 to −0.319) as were changes in job demands (B depression=0.386; 95% CI 0.245 to 0.527; B anxiety=0.434; 95% CI 0.267 to 0.601). Excluding people with severe symptoms at baseline did not alter the findings; however, path analyses indicated that depression may precede a worsening of work conditions.

Conclusion: Among mid-aged employees, deteriorating work conditions may amplify population health burdens, especially anxiety. Furthermore, better quality jobs, combining an array of positive conditions, could alleviate major population health burdens.

Age differences in psychosocial predictors of positive and negative affect: A longitudinal investigation of young, midlife, and older adults. Windsor, T.D., & Anstey, K.J. (2010  Psychology and Aging 25 (3), 641–652

Age group differences in self-reported supportive, aversive, ambivalent, and indifferent partner relations were examined in a large sample of midlife (aged 40-44 at baseline, n = 1,719) and older (aged 60-64 at baseline, n = 1,675) married and partnered adults assessed on two occasions 4 years apart. Older adults, particularly older men, were more likely to rate their relationship as supportive and less likely to rate their relationship as aversive relative to midlife adults. Midlife adults were more likely to provide ambivalent or indifferent assessments (as opposed to supportive assessments) of their relationship relative to older adults. Results are discussed in the context of possible developmental changes in interpersonal and intimate relations occurring in middle and older adulthood.

Level of cognitive performance as a correlate and predictor of health behaviors that protect against cognitive decline in late life: The PATH Through Life Study.  Anstey, K. J., Low, L-F., Christensen, H. & Sachdev, P. (2009), Intelligence, 37, 600-606.

This paper examined the association between cognitive ability and health behaviours over time. It was found that those who performed better in the cognitive testing had higher levels of precautionary health behaviour such as taking vitamins and minerals and physical activity. However, the greatest improvement in health behaviours over four years was seen in those who performed more poorly in the Wave 1 cognitive testing. This suggests that other factors such as increasing health education, greater affluence or more available health education may influence improved health behaviours, particularly in those with lower cognitive scores.

Incidence of self-reported brain injury and the relationship with substance abuse: Findings from a longitudinal community survey. Tait RJ, Anstey KJ, Butterworth P. (2010). BMC Public Health. 10: DOI 10.1186/1471-2458-1110-1171.

Serious brain injury (BI) is known to have adverse and persistent outcomes. However, ‘mild’ or ‘moderate’ BI, which often does not result in hospital treatment, accounts for half the total days of disability attributed to BI. This report looks at mild and moderate BI reported in a community sample. Males and those in the 20+ cohort had increased risk of BI. Sports injury was the most frequent cause of BI with traffic accidents being a greater proportion of the moderate cases. Unlike finding from clinical studies, neither alcohol nor marijuana problems at Wave 1 were predictors of BI at wave 2 and BI was not a predictor of developing substance use problems at wave 2.

Risk factors of transition from normal cognition to mild cognitive disorder: The PATH through life study. Cherbuin, N., Réglade-Meslin, C., Kumar, R., Jacomb, P., Easteal, S., Christensen, H., Sachdev, P., Anstey, K. J. (2009). Dementia and Geriatric Cognitive Disorders, 28, 47-55.

The aim of this study was to identify physical and mental health predictors of transition from normal cognition the Mild Cognitive Impairment in the PATH 60+ cohort. The main predictors were past alcohol intake, current anxiety and depression medication, increased systolic blood pressure and past smoking. Strategies targeted at managing these risk factors may have benefits in preventing mild cognitive decline in relatively healthy people.

Cognition in pregnancy and motherhood: prospective cohort study. Christensen H, Leach LS Mackinnon A (2010) The British Journal of Psychiatry 196; 126-132

Research has reported that pregnant women and mothers become forgetful. However, in these studies women are not recruited prior to pregnancy so it is not possible to compare memory before and after pregnancy. Using PATH data we were able to look at this in the 20+ age cohort. No significant differences in cognitive change were found as a function of pregnancy or motherhood although late pregnancy was associated with deterioration one of four tests of memory and cognition.

Financial hardship, socio-economic position and depression: Results from the PATH Through Life Survey  Butterworth P, Rodgers B, Windsor TD. (2009). Social science and Medicine July 69 (2): 229-237

There is known to be a strong association between financial hardship and depression but the relationship is unclear. It was found that current financial hardship, but not past hardship, was strongly associated with depression, suggesting that addressing deprivation may be an effective strategy to moderate socio-economic inequalities in mental health.

Volunteering and psychological wellbeing among young-old adults: How much is too much? Windsor, T. D., Anstey, K. J., & Rodgers, B. (2008). The Gerontologist, ;48, 59-70.

Data from the second wave of the PATH project was used to investigate relationships between 64 to 68 year-olds' time spent volunteering and levels of psychological well-being. Participants who reported taking part in moderate levels of volunteer work also reported higher levels of well-being than both those who did not volunteer, and those who engaged in more than around 15 hours of voluntary work per week. The results suggest that taking part in volunteer activity in later life not only has broader social benefits, but is also associated with benefits to the individual who volunteers. However, there appears to be an optimal level of volunteering for maintaining wellbeing.

Pre-trauma and post-trauma neurocognitive functioning and PTSD symptoms in a community sample of 1599 young adults. Parslow RA, Jorm AF. (2007) American Journal of Psychiatry 164:509-515.

Since trauma experiences are generally random and unpredictable, it is very difficult for researchers to have access to such pre-trauma measures. In the PATH Through Life project, 2404 participants in aged 20 to 24 years were interviewed for this longitudinal study and 2139 (89.0%) were then re-interviewed after the Canberra bushfires that occurred in January 2003. Neurocognitive measures were obtained from these trauma-exposed participants both before and after the trauma. Researchers found that PATH participants who screened positive for post traumatic stress disorder (PTSD) had significantly poorer neurocognitive skills prior to the trauma experience, but that, in the main, their measures of these skills did not decline significantly as a result of their being exposed to this trauma or experiencing PTSD symptoms. It was concluded from this study that having poorer neurocognitive skills following exposure to trauma may not be the result of the trauma experience and related PTSD symptoms. Instead having poorer neurocognitive abilities is likely to be a risk factor for developing PTSD.

Total and regional grey matter volume is not related to APOE*E4 status in a community sample of middle-aged individuals. Cherbuin, N., Anstey, K. J., Sachdev, P., Maller, J. J., Meslin, C., Mack, H., Wen, W., & Easteal, S. (2007). Journal of Gerontology: Medical Sciences. 24, 348-62

Apolipoprotein or APOE is the main genetic risk factor for non-familial Alzheimer’s disease. Carriers of one of the variants of the APOE gene, the E4 allele, have been shown to be at higher risk of brain atrophy, and to be affected by cognitive impairment earlier and more often than those who do not carry this form of APOE. Researchers investigated whether APOE E4 effects were already detectable in this relatively young and healthy 60-64year old in the PATH study. They compared measures of cerebral gray matter between the APOE E4 carriers and non-carriers as well as the volume of the hippocampus, a brain structure involved in memory function which is affected early in dementia and found no differences. These recently published results are important as they show that the negative effects associated with APOE E4 demonstrated in other samples of ageing individuals are not yet detectable in the early sixties in a relatively healthy, well educated, and affluent sample.

White matter hyperintensities in the forties: The prevalence and topography in an epidemiological sample aged 44-48.  Wen, W., Chen, X., Anstey, K. J, & Sachdev, P. S. (7/03/08). Human Brain Mapping

The brains of elderly individuals often show subtle changes in the white matter, which have become of increasing interest with the wide availability of MRI scans. It is thought that these changes are due to a gradual increase in abnormalities in small blood vessels of the brain as we age. The changes are more prominent in those who have high blood pressure or diabetes, or have other risk factors for blood vessel disease such as smoking, high cholesterol, obesity and heart disease. Previous work done in the PATH Through Life Study has shown that >90% of otherwise healthy individuals in their early 60s have some of these changes on MRI. Even through subtle, they are related to mild slowing of movement and the speed of information processing in the brain. We recently examined an even younger cohort of healthy individuals all in the mid to late 40s, for these lesions. Small white matter lesions were seen in 1 in 2 individuals in this age group. They were slightly more common in women and in current smokers or abusers of alcohol but not hypertension or the levels of blood pressure. Our work, which is quite unique internationally, suggests that interventions to prevent WMHs should begin early in life. This is one area of preventative medicine that is likely to pay dividends in protecting our brains as we grow old.

Follow-up of Mild Cognitive Impairment and Related Disorders Over 4 years in Adults in Their Sixties: The PATH Through Life Study.  Anstey, K. J., Cherbuin, N., Christensen, H., Burns, R., Reglade-Meslin, C., Salim, A., Kumar, R., Jorm, A. F., Sachdev, P. (2008) Dementia and Geriatric Cognitive Disorders. 26:226-233.

Researchers from PATH aimed to estimate incidence rates of Mild Cognitive Impairment and related disorders, and conversion to dementia. After analyzing the cognitive assessments and clinical data from PATH wave 2 they found that the annual incidence of dementia was 0.25%. Prevalence of Mild Cognitive Impairment was 4.2%, Age Associated Memory Impairment was 2.4%, Age-Associated Cognitive Decline was 7.6%, Mild Neurocognitive Disorders was 12.9% and Other Cognitive Disorder was 7.3%. The prevalence of any diagnosis of any mild cognitive disorder (Any-MCD) was 29.5% and the annual incidence rate for Any-MCD was 5.7%. Agreement for specific diagnoses between Waves 1 and 2 was fair to poor (0 to 47.0%) but agreement for Any-MCD over 4 years was 89.0%. We concluded that diagnoses of mild cognitive disorders do not predict dementia at four year follow-up in young-old adults. Prevalence rates for mild cognitive disorders vary greatly depending on criteria and time of assessment.

Education, atrophy and cognitive change in an epidemiological sample of early old age.  Christensen, H., Batterham, P., MacKinnon, A., Anstey K.J. & Sachdev, P. (2009). American Journal of Geriatric Psychiatry 17:3 218-226.

The brain reserve hypothesis proposes that the endowment of greater ‘reserve’ offsets the biological effects of ageing and disease. Very few research investigations have directly tested the brain reserve hypothesis and this has been particularly the case for younger old age groups, including individuals in their mid or late 60s. Years of education and brain size (as measures of reserve) were examined in a sample of 472 PATH participants aged 60-64 years at baseline. The association between these measures and brain atrophy, white matter hyperintensities (WMH) and cognitive decline were measured. Although there were declines on a test of cognitive speed, there was no protection conferred by the possession of a larger brain or by higher level of formal education. There were no relationships established between indices of brain health (WMH, brain atrophy) and cognitive decline. These results are not consistent with the brain reserve hypothesis, but changes in cognition were small and the contribution of reserve may be minor in early old age.

Gender differences in the endorsement of symptoms for depression and anxiety: Are gender biased items responsible?  Leach, L.S., Christensen, H., & Mackinnon, A.J (2008). Journal of Nervous and Mental Disease, 196(2), 128-135.

Research evidence shows that women experience higher levels of depression and anxiety than men do, however, the reasons for these gender differences remain unclear. PATH researchers have examined possible explanations. Initially they hypothesised that item bias in the scales used to measure depression and anxiety might be responsible for gender differences in overall levels of symptomology, however, this hypothesis was not supported. Following on from this work, a second paper examined potential psychosocial risk factors (mediators) for the preponderance of depression and anxiety in women. This research found that women across three age groups were more exposed to negative interpersonal events and childhood adversity than men were, and that these factors were associated with their greater psychological distress. Women were also found to more often possess harmful personality characteristics and coping styles than men, such as low levels of mastery, as well as high levels of behavioural inhibition, negative rumination and neuroticism. They also were more likely to have poor physical health and low participation in physical activity.

Association of Type 2 Diabetes with Depression, Brain Atrophy and Reduced Fine Motor Speed in a 60-64 year old Community Sample. Kumar, R. Anstey, K.J. Cherbuin, N. Wen, W., Sachdev, P. (2008) American Journal of Geriatric Psychiatry 16: 989-998

The complex relationship of type 2 diabetes to depression, cognition, and structural brain abnormalities is poorly understood. We investigated this in the 60-64 year old PATH MRI sub-study participants. In this sub-sample 39 subjects had type 2 diabetes and 428 did not have this disorder. All underwent physical examinations, assessment of depression, cognitive assessments, brain magnetic resonance imaging scans and fasting blood tests. Descriptive analyses showed that those with diabetes were more likely to have poor physical health, a bigger body mass index, and higher scores of depression and anxiety compared with those without diabetes. Having diabetes was also found to be associated with greater total brain atrophy and larger CSF volumes and poorer fine motor dexterity and these were found to be independent of depression, vascular risk factors and small vessel disease of the brain.

Factors distinguishing suicide attempters from suicide ideators in a community sample: Social issues and physical health problems. Fairweather, A. K., Anstey, K. J., Rodgers, B., & Butterworth, P. (2006) Psychological Medicine, 36, 1235-46

Age and gender differences among suicidal ideators: prevalence and correlates. Fairweather, A. K., Anstey, K. J., Rodgers, B., Jorm, A. F., & Christensen, H. (2007). Journal of Nervous and Mental Disease, 195, 130-136

There is currently a lack of epidemiological data on suicidal behaviour in the field of suicidology, and more specifically in the Australian context. PATH is an important study for examining suicidality because it addresses the issue of suicidality across the adult life course. Analyses of PATH data have shown that men aged 60-64 were 2/3 more likely to have suicidal thoughts than their female counterparts and being underemployed also dramatically increased the likelihood of experiencing suicidal ideation within this age group. However, perception of mastery over one’s life was highly protective against suicidal ideation among younger and middle-aged adults.

We have also conducted research to find out what distinguishes those who have suicial ideation, from those who go on to attempt suicide. This distinction is critical for the targeting of prevention programs, yet there has been little research that has allowed for this distinction to be made. Again, differences were found across age and gender. Unemployment was found to be particularly important during middle age, where suicide ideators without work were nearly nine times more likely to attempt than those who worked. Further, male ideators with a physical illness were nearly four times more likely to report a suicide attempt. Another key finding was that depression and anxiety did not distinguish between those who reported ideation, and ideators who also attempted.