The combination of olfactory dysfunction and depression increases the risk of incident dementia in older adults.

OBJECTIVES: Olfactory dysfunction and depression are common in later life, and both have been presented as risk factors for dementia. Our purpose was to investigate the associations between these two risk factors and determine if they had an additive effect on dementia risk. DESIGN: Olfactory function was assessed using the Brief Smell Identification Test (BSIT), and depression was classified using a combination of the 15-item Geriatric Depression Scale (GDS) score and current antidepressant use. Cross-sectional associations between depression and olfactory function were examined using correlations. Cox regression analyses were conducted to examine the longitudinal relationship between olfaction and depression and incident dementia across 12-years of follow-up. PARTICIPANTS: Participants were 780 older adults (aged 70-90 years; 56.5% female) from the Sydney Memory and Ageing Study (MAS) without a diagnosis of dementia at baseline. RESULTS: Partial correlation revealed a nonsignificant association between baseline depression and olfactory function after accounting for covariates (r = -.051, p = .173). Cox regression showed that depression at baseline (hazard ratio = 1.706, 95% CI 1.185-2.456, p = .004) and lower BSIT scores (HR = .845, 95%CI .789-.905, p < .001) were independently associated with a higher risk of incident dementia across 12 years. Entering both predictors together improved the overall predictive power of the model. CONCLUSIONS: Lower olfactory identification scores and depressive symptoms predict incident dementia over 12 years. The use of BSIT scores and depression in conjunction provides a greater ability to predict dementia than either used alone. Assessment of olfactory function and depression screening may provide clinical utility in the early detection of dementia.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Dose-response relationship between late-life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium.

INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults. RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week). DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing.

INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.

Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. METHODS: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. RESULTS: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th-75th percentile: 1.21-4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (-0.053 SD/year [95% CI, -0.073 to -0.033]; P<0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=-0.078 SD/year [95% CI, -0.11 to -0.045]; P<0.001 for global cognition in a subgroup analysis). CONCLUSIONS: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney.

The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.

Association of Prediabetes and Type 2 Diabetes With Cognitive Function After Stroke: A STROKOG Collaboration Study.

Background and Purpose- Type 2 diabetes mellitus (T2D) is associated with cognitive impairment and an increased risk of dementia, but the association between prediabetes and cognitive impairment is less clear, particularly in a setting of major cerebrovascular events. This article examines the impact of impaired fasting glucose and T2D on cognitive performance in a stroke population. Methods- Seven international observational studies from the STROKOG (Stroke and Cognition) consortium (n=1601; mean age, 66.0 years; 70% Asian, 26% white, and 2.6% African American) were included. Fasting glucose level (FGL) during hospitalization was used to define 3 groups, T2D (FGL ≥7.0 mmol/L), impaired fasting glucose (FGL 6.1-6.9 mmol/L), and normal (FGL <6.1 mmol/L), and a history of diabetes mellitus and the use of a diabetes mellitus medication were also used to support a diagnosis of T2D. Domain and global cognition Z scores were derived from standardized neuropsychological test scores. The cross-sectional association between glucose status and cognitive performance at 3 to 6 months poststroke was examined using linear mixed models, adjusting for age, sex, education, stroke type, ethnicity, and vascular risk factors. Results- Patients with T2D had significantly poorer performance in global cognition (SD, -0.59 [95% CI, -0.82 to -0.36]; P<0.001) and in all domains compared with patients with normal FGL. There was no significant difference between impaired fasting glucose patients and those with normal FGL in global cognition (SD, -0.10 [95% CI, -0.45 to 0.24]; P=0.55) or in any cognitive domain. Conclusions- Diabetes mellitus, but not prediabetes, is associated with poorer cognitive performance in patients 3 to 6 months after stroke.

Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study.

BACKGROUND: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. METHODS: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. RESULTS: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. CONCLUSION: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.

Factors associated with odour identification in older Indonesian and white Australian adults.

BACKGROUND AND AIMS: Among older adults, olfactory dysfunction is associated with cognitive impairment, lower quality of life, and increased mortality. While age is a risk factor for olfactory dysfunction, other risk factors are less well understood, and may vary between ethno-regional groups. This study investigated how associations between odour identification (OI) and various risk factors, as well as cognition and language ability, differed or were similar in two distinct ethno-regional groups of older adults. METHODS: This cross-sectional study used data from two cohorts: 470 Indonesians (aged 67.4 ± 7.4 years) and 819 white Australians (aged 78.7 ± 4.8 years). Univariate and multivariate analyses explored whether OI test scores were associated with age, sex, education, cholesterol levels, apolipoprotein E ε4 status, smoking, diabetes, hypertension and depression scale scores, or with Mini-Mental State Examination (MMSE) and language test performance. RESULTS: Univariate analyses identified some factors associated with OI scores in both Indonesians and white Australians, including older age and smoking with lower scores, and MMSE and language test performance with higher scores. Multivariate analyses yielded different and mutually exclusive patterns of associations in the two ethno-regional groups, with language test scores significantly associated with higher OI scores in Indonesians, and age, being male, smoking, having diabetes and higher depression scale scores significantly associated with lower OI scores in white Australians. CONCLUSION: Ethno-regional differences may need consideration in the attempt to fully understand associations between OI and negative outcomes like dementia and mortality, and interventions for olfactory dysfunction might need to be tailored to specific ethno-regional groups. However, the difference in mean age between cohorts is a limitation of this study, and future studies should aim to compare populations with similar age distributions.

A cross-national study of depression in preclinical dementia: A COSMIC collaboration study.

INTRODUCTION: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. METHODS: Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics. RESULTS: A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates. DISCUSSION: The results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Visual memory tests enhance the identification of amnestic MCI cases at greater risk of Alzheimer's disease.

OBJECTIVES: To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer's disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests. PARTICIPANTS: 4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates. RESULTS: All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66 - 9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC. CONCLUSIONS: Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI.

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study.

BACKGROUND: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. METHODS AND FINDINGS: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. CONCLUSIONS: Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.

Neuroticism scores increase with late-life cognitive decline.

OBJECTIVE: Neuroticism has been reported as both a risk factor for cognitive decline and a characteristic that increases in parallel with the development of mild cognitive impairment (MCI) and dementia. However, the evidence for these associations is inconclusive, and whether effects are stronger for particular cognitive domains is unknown. We investigated these issues and determined if associations differ among different components of neuroticism. METHODS: A neuroticism scale (NEO-FFI) and neuropsychological test battery were administered to 603 older adults without dementia, with 493 of these reassessed two years later. Diagnoses of MCI and dementia (at follow-up) were made, and global cognition and performance in six cognitive domains quantified. The neuroticism components were negative affect, self-reproach, and proneness to psychological distress. RESULTS: For the whole sample, neuroticism scores remained stable between baseline (15.3 ± 7.0) and follow-up (15.5 ± 7.0), as did all neuroticism component scores. However, there were declines in global cognition (p < 0.05) and particular cognitive domains (p < 0.001). Higher neuroticism was associated with poorer cognition cross-sectionally (p < 0.01), but did not predict cognitive decline. For 43 participants who developed incident MCI or dementia, there were increases in neuroticism (15.3 ± 6.4 to 17.1 ± 8.3, p < 0.05) and negative affect (p < 0.05). Declines in all cognitive measures except executive function were associated with increases in neuroticism and component scores (p < 0.05). CONCLUSIONS: Late-life cognitive decline is associated with an increase in neuroticism scores. However, associations vary between different cognitive domains and components of neuroticism. An increase in neuroticism or negative affect scores may be a sign of MCI or dementia.

A longitudinal study of brain atrophy over two years in community-dwelling older individuals.

Most previous neuroimaging studies of age-related brain structural changes in older individuals have been cross-sectional and/or restricted to clinical samples. The present study of 345 community-dwelling non-demented individuals aged 70-90years aimed to examine age-related brain volumetric changes over two years. T1-weighted magnetic resonance imaging scans were obtained at baseline and at 2-year follow-up and analyzed using the FMRIB Software Library and FreeSurfer to investigate cortical thickness and shape and volumetric changes of subcortical structures. The results showed significant atrophy across much of the cerebral cortex with bilateral transverse temporal regions shrinking the fastest. Atrophy was also found in a number of subcortical structures, including the CA1 and subiculum subfields of the hippocampus. In some regions, such as left and right entorhinal cortices, right hippocampus and right precentral area, the rate of atrophy increased with age. Our analysis also showed that rostral middle frontal regions were thicker bilaterally in older participants, which may indicate its ability to compensate for medial temporal lobe atrophy. Compared to men, women had thicker cortical regions but greater rates of cortical atrophy. Women also had smaller subcortical structures. A longer period of education was associated with greater thickness in a number of cortical regions. Our results suggest a pattern of brain atrophy with non-demented people that resembles a less extreme form of the changes associated with Alzheimer's disease (AD).

Progression of cognitive impairment in stroke/TIA patients over 3†years.

OBJECTIVES: To examine how cognitive deficits progress in the years following a stroke or transient ischaemic attack (TIA). METHODS: A follow-up study, with neuropsychological and MRI assessments undertaken 3 years after baseline assessments made 3-6 months poststroke in 183 stroke/TIA patients and 97 healthy controls participating in the Sydney Stroke Study. Additional measures included cardiovascular risk factors and apolipoprotein E (APOE) genotype. RESULTS: Stroke/TIA patients had poorer cognitive function and more vascular risk factors than controls at baseline, but did not show greater decline in cognitive function over 3 years except for verbal memory. Patients with a subsequent stroke/TIA showed greater decline in global cognitive function and a number of domains. Rates of incident dementia were 5.9% per year in patients and 0.4% in controls. Both groups showed increased atrophy of the hippocampus, amygdala and whole brain, and an increase in white matter hyperintensities over 3 years; whole brain atrophy was greater in patients. Cognitive decline was greater in women and in those with smaller hippocampi at baseline. For patients without a subsequent stroke/TIA, those with smaller hippocampi or the APOE ε4 allele had greater global cognitive and verbal memory decline. CONCLUSIONS: In poststroke patients, cognitive decline was not greater than in comparison subjects, except for verbal memory, unless they had another stroke/TIA. However, dementia incidence was higher in patients, as might be expected from their poorer baseline cognitive functioning. Smaller hippocampi were associated with an increased risk of decline in memory, and APOE ε4 was a risk factor in those without a subsequent stroke/TIA.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.