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Understanding dementia and cognitive impairment is a global effort needing data from multiple sources across diverse ethno-regional groups. Methodological heterogeneity means that these data often require harmonization to make them comparable before analysis. We discuss the benefits and challenges of harmonization, both retrospective and prospective, broadly and with a focus on data types that require particular sorts of approaches, including neuropsychological test scores and neuroimaging data. Throughout our discussion, we illustrate general principles and give examples of specific approaches in the context of contemporary research in dementia and cognitive impairment from around the world.

Objectives Normal adult aging is associated with changes in social cognition. Although 4 social cognitive domains have been identified (social perception, theory of mind [ToM], affective empathy, and social behavior), no study has tested all 4 domains concurrently in a life-span sample, limiting understanding of the relative magnitude of age-related changes across domains. This study addresses this gap by providing the first assessment of all 4 social cognitive domains in an adult life-span sample. Methods Three hundred and seventy-two participants ranging from 18 to 101 years of age took part in this study. Participants completed a testing battery that assessed social perception, ToM, affective empathy, and social behavior, as well as broader cognitive function and well-being. Results The results showed that adult aging is associated with multidirectional changes in social cognitive abilities, with ToM and social perception showing nonlinear decline across much of the life-span, and affective empathy and social behavior showing improvement. Age remained a significant predictor of all 4 social cognitive domains, even after accounting for broader cognitive function. Weak associations emerged between some of the social cognitive abilities and and indices of broader well-being. Discussion These findings provide novel and important evidence that normative aging is associated with both gains and losses in social cognition that occur at distinct points of the adult life-span, and that are at least partially independent of general age-related cognitive decline.

Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear.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.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).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.

Background: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. Objective: This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. Method: We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. Result: The meta-analytic results indicated that both education and occupational complexity were independently associated with increased dementia-free survival time, with 28%of the effect of education mediated by occupational complexity. There was evidence of threshold effects for education, with increased dementia-free survival time associated with ‘high school completion’ or ‘above high school’ compared to ‘middle school completion or below’. Conclusion: Using datasets from a wide range of geographical regions, we found that both early life education and adulthood occupational complexity were independently predictive of dementia. Education and occupational experiences occur during early life and adulthood respectively, and dementia prevention efforts could thus be made at different stages of the life course.

To examine the moderation effects of hormonal factors on the associations between vascular risk factors and white matter hyperintensities in men and women, separately. White matter hyperintensities were automatically segmented and quantified in the UK Biobank dataset (N = 18,294). Generalised linear models were applied to examine (1) the main effects of vascular and hormonal factors on white matter hyperintensities, and (2) the moderation effects of hormonal factors on the relationship between vascular risk factors and white matter hyperintensities volumes. In men with testosterone levels one standard deviation higher than the mean value, smoking was associated with 27.8% higher white matter hyperintensities volumes in the whole brain. In women with a shorter post-menopause duration (one standard deviation below the mean), diabetes and higher pulse wave velocity were associated with 28.8% and 2.0% more deep white matter hyperintensities, respectively. These findings highlighted the importance of considering hormonal risk factors in the prevention and management of white matter hyperintensities.

Background: The interaction between cerebral vessel disease (CVD) pathology and Alzheimer’s disease (AD) pathology in the development of dementia is controversial. We examined the association of cerebral vascular neuropathology and cerebrovascular risk factors with the mild stage of Alzheimer's dementia and cognitive function. Methods: This cross-sectional study included men and women aged 60 years or over who had yearly clinical assessments and had agreed to brain autopsy at the time of death, and who contributed to data stored at the National Alzheimer's Coordinating Center (NACC) in the USA. Cognitively normal and impaired subjects with presumptive aetiology of AD, including mild cognitive impairment (ADMCI) and dementia (Alzheimer’s dementia), and with complete neuropathological data, were included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Systematic neuropathological assessments documenting the severity of cerebral vascular pathology were included. Logistic and linear regression analyses corrected for age at death, sex and Lewy body pathology were used to examine associations of vessel disease with the severity of Alzheimer's disease dementia, and cognitive function, respectively. Results: No significant relationship was observed between late-life risk factors and Alzheimer’s dementia. The severity of arteriosclerosis and presence of global infarcts/lacunes were related to mild Alzheimer’s dementia (B=0.423, p Conclusion: Our study found the significant relation of global, old, acute/subacute and regional cerebral vascular pathologies, but not white matter rarefaction, to the onset and severity of Alzheimer’s dementia. We also showed that late-life risk factors were found to have no relation with Alzheimer’s dementia, and the increased risk of dementia with APOE ε4 is not mediated by CVD. The best interpretation of these findings is that CVD has a potential additive effect with AD pathologies in the development and progression of what is clinically diagnosed as Alzheimer's dementia.

Objective: To examine the moderation effects of hormonal factors on the associations between vascular risk factors and white matter hyperintensities (WMH) in men and women, separately. Methods: WMH were automatically segmented and quantified in the UK Biobank dataset (N = 18,294). Generalised linear models were applied to examine 1) the main effects of vascular (body mass index, hip to waist ratio, pulse wave velocity, hypercholesterolemia, diabetes, hypertension, smoking status) and hormonal (testosterone levels, contraceptive pill, hormone replacement therapy, menopause) factors on WMH, and 2) the moderation effects of hormonal factors on the relationship between vascular risk factors and WMH volumes. Results: In men with testosterone levels one standard deviation (SD) higher than the mean value, increased body mass index and pulse wave velocity, and smoking were associated with higher WMH volumes. The association between body mass index and WMH was more significant in the periventricular white matter regions, whilst the relationship between pulse wave velocity and WMH was restricted to deep white matter regions. Men with low testosterone levels (one SD below the mean level) showed a significant association between hypercholesterolemia and higher deep WMH volumes. Hypertensive women showed higher WMH volumes than women without hypertension regardless of whether hormone replacement therapy was used. However, higher WMH volumes, especially in the deep white matter regions, were found in women who did not use hormone replacement therapy or use it for a shorter duration. Conclusion: These findings highlighted the importance of considering hormonal risk factors in the prevention and management of WMH.

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.

Background While midlife hypertension is deleterious, late-life hypertension has been associated with better cognitive outcomes in several studies. Many questions remain, including the relative benefit or harm of a blood pressure (BP) target and antihypertensive therapy of Methods The Sydney Memory and Aging Study (n = 1015) comprises a cohort of 70- to 90-year-olds, who were followed biennially for 8 years. Global cognition was assessed with a battery of 10 neuropsychological tests. Blood pressure was measured at Waves 1 and 2 and classified into 3 systolic groupings: group 1 (≤120 mmHg), group 2 (121–140 mmHg), and group 3 (>140 mmHg). Multiple regression, linear mixed modeling, and Cox regression examined the effect of BP and antihypertensives. Results There were no overall significant differences in global cognition or dementia between the disparate BP groups. However, in those not taking antihypertensives, the systolic BP (SBP) > 140 mmHg group had a significantly worse global cognitive trajectory compared to SBP ≤ 120 mmHg (b = −0.067, 95% CI [−0.129, −0.006], p = .030). Within the SBP ≤ 120 mmHg group those taking antihypertensives had significantly worse global cognition trajectories compared to those not taking antihypertensives even when controlling for past history of hypertension (b = −0.077, 95% CI [−0.147, −0.007], p = .030). Conclusions Untreated hypertension in old age is related to worse global cognitive decline. However, ongoing treatment at new recommendations of lower SBP targets may be related to poorer cognitive decline and should be considered carefully in older populations.

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 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 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.

Background Depression is a common problem in older adults. The 15-item Geriatric Depression Scale (GDS-15) is a widely used psychometric tool for measuring depression in the elderly, but its psychometric properties have not been yet rigorously investigated. The aim was to evaluate psychometric properties of the GDS-15 and improve precision of the instrument by applying Rasch analysis and deriving conversion tables for transformation of raw scores into interval level data. Methods The data was extracted from the prospective cohort Sydney Memory and Ageing Study of initially not demented individuals aged 70 years and older. The GDS-15 items scores of 212 participants (47.2% males) were analysed using the dichotomous Rasch model. Results Initially poor reliability of the GDS-15, Person Separation Index (PSI) = 0.68, was improved by combining locally dependent items into seven super-items. These modifications improved reliability of the GDS-15 (PSI = 0.78) and resulted in the best Rasch model fit (χ2(28)=37.72, p = =0.104), strict unidimensionality and scale invariance across personal factors such as gender, diagnostic and language background. Limitations Presence of participants with cognitive impairment may be a potential limitation. Conclusions Reliability and psychometric characteristics of the GDS-15 were improved by minor modifications and now satisfy expectations of the unidimensional Rasch model. By using Rasch transformation tables published here psychiatrists, psychologists and researchers can transform GDS raw scores into interval-level data, which improves reliability of the GDS-15 without the need to modify its original response format. These findings increase accuracy of clinical psychometric assessments, leading to more precise diagnosis of depression in the elderly.

Purpose of review Cognitive decline is frequently reported after hospitalisation in the contexts of surgery, delirium and critical care. The question not adequately addressed is whether all types of acute hospitalisations increase the risk of cognitive decline. As acute hospitalisations are common in the elderly, who are also vulnerable to cognitive decline, this possible association is of significant concern. Recent findings This review summarises cognitive outcomes from recent observational studies investigating acute hospitalisation (emergent and elective) in older age adults. Studies were identified from searching Medline, Embase and PsycINFO databases and citations lists. The highest incidence of cognitive decline has been reported following critical care admissions and admissions complicated by delirium, although all types of acute hospitalisations are implicated. Age is the most consistent risk factor for cognitive decline. Several etiological and therapeutic aspects are being investigated, particularly the measurement of inflammatory biomarkers and treatment with anti-inflammatory medications. Summary Acute hospitalisation for any reason appears to increase the risk of cognitive decline in older adults, but the cause remains elusive. Future research must clarify the nature and modifiers of posthospitalisation cognitive change, a priority in the face of an ageing population.

Graphical abstract, Vascular dementia (VaD) is a complex neurocognitive disorder secondary to a variety of cerebrovascular lesions. Numerous studies have shown that lipid metabolism is involved in the pathobiology of the disease. We examined the plasma lipid profiles in VaD, with the expectation of identifying reliable lipid biomarkers for VaD. 49 VaD patients and 48 healthy controls were recruited from Bankstown-Lidcombe Hospital in Sydney, Australia. Lipids were extracted by single phase 1-butanol/methanol, and untargeted analysis was performed by liquid chromatography coupled-mass spectrometry (LC–MS/MS). Univariate analysis of variance was used to examine the differences in lipid classes and individual lipids between VaD and control groups. In an independent sample of 161 subjects from the Older Australian Twins Study (OATS), elastic net penalization for the generalized linear model (Glmnet) and Random Forest were applied to the lipid levels to subcategorise the sample into vascular cognitive impairment and controls. Most lipids belonging to the classes of ceramides (Cer), cholesterol esters (ChE) and phospholipids were significantly lower in VaD plasma, while glycerides were elevated compared to controls. Levels of ChE, Cer and the two lipid classes together achieved the best accuracy in discriminating VaD from controls, with more than 80% accuracy. The probable VaD group in the OATS sample predicted by the lipid levels showed greater impairment in most cognitive domains, especially attention and processing speed and executive function from controls but did not differ in white matter hyperintensities and DTI measures. As a conclusion, plasma lipids levels, in particular Cer and ChE, are abnormal in VaD and may help discriminate them from healthy controls. Understanding the basis of these differences may provide insights into the pathobiology of VaD.

Objective: Several movement disorders develop secondary to the use of psychotropic drugs, for which multiple symptom rating scales are in common use. We planned to develop the Unified Drug-Induced Movement Scale (UDIMS) to assess the severity and impact of drug-induced dyskinesia, tremor, drug-induced parkinsonism, akathisia, dystonia and myoclonus with a single instrument. Methods: Based on a literature review, consultation and pilot work, a 12-item instrument was developed, with each item rated on a 0-4 scale. The clinimetric properties of UDIMS were examined in 53 psychiatric patients on psychotropic medications, using established ratings scales for validation. The factor structure of the scale was examined, and the movement disorder correlates of distress and disability were determined. Results: The instrument has good inter-rater reliability. Its correspondence with three other scales - Abnormal Involuntary Movements Scale, Simpson-Angus Scale and Prince Henry Hospital Akathisia Scale - for the relevant items was high. A principal components analysis yielded four factors, considered to represent tremor, parkinsonism, akathisia and dyskinesia. Overall movement-disorder related disability was related to parkinsonism and dyskinesia, while distress to all four components. Conclusions: UDIMS is a reliable and valid scale to quantify a range of drug-induced movement disorders (DIMDs), that obviates the need for the use of multiple rating scales. Its widespread use by both clinicians and researchers, and further refinement based on this, will help promote the detection and treatment of drug-induced movement disorders, thereby reducing both distress and disability.

Background: Cerebral small vessel disease (SVD) and Alzheimer’s disease pathology, namely amyloid-β (Aβ) deposition, commonly co-occur. Exactly how they interact remains uncertain. Objective: Using participants from the Alzheimer’s Disease Neuroimaging Initiative (n = 216; mean age 73.29±7.08 years, 91 (42.1%) females), we examined whether the presence of vascular risk factors and/or baseline cerebral SVD was related to a greater burden of Aβ cross-sectionally, and at 24 months follow-up. Method: Amyloid burden, assessed using 18F-florbetapir PET, was quantified as the global standardized uptake value ratio (SUVR). Multimodal imaging was used to strengthen the quantification of baseline SVD as a composite variable, which included white matter hyperintensity volume using MRI, and peak width of skeletonized mean diffusivity using diffusion tensor imaging. Structural equation modeling was used to analyze the associations between demographic factors, Apolipoprotein E ɛ4 carrier status, vascular risk factors, SVD burden and cerebral amyloid. Results: SVD burden had a direct association with Aβ burden cross-sectionally (coeff. = 0.229, p = 0.004), and an indirect effect over time (indirect coeff. = 0.235, p = 0.004). Of the vascular risk factors, a history of hypertension (coeff. = 0.094, p = 0.032) and a lower fasting glucose at baseline (coeff. = –0.027, p = 0.014) had a direct effect on Aβ burden at 24 months, but only the direct effect of glucose persisted after regularization. Conclusion: While Aβ and SVD burden have an association cross-sectionally, SVD does not appear to directly influence the accumulation of Aβ longitudinally. Glucose regulation may be an important modifiable risk factor for Aβ accrual over time.

Objectives:Computerised neuropsychological assessments (CNAs) are proposed as an alternative method of assessing cognition to traditional pencil-and-paper assessment (PnPA), which are considered the “gold standard” for diagnosing dementia. However, limited research has been conducted with culturally and linguistically diverse (CALD) individuals. This study investigated the suitability of PnPAs and CNAs for measuring cognitive performance in a heterogenous sample of older, Australian CALD English-speakers compared to a native English-speaking background (ESB) sample.Methods:Participants were 1037 community-dwelling individuals aged 70–90 years without a dementia diagnosis from the Sydney Memory and Ageing Study (873 ESB, 164 CALD). Differences in the level and pattern of cognitive performance in the CALD group were compared to the ESB group on a newly developed CNA and a comprehensive PnPA in English, controlling for covariates. Multiple hierarchical regression was used to identify the extent to which linguistic and acculturation variables explained performance variance.Results:CALD participants’ performance was consistently poorer than ESB participants on both PnPA and CNA, and more so on PnPA than CNA, controlling for socio-demographic and health factors. Linguistic and acculturation variables together explained approximately 20% and 25% of CALD performance on PnPA and CNA respectively, above demographics and self-reported computer use.Conclusions:Performances of CALD and ESB groups differed more on PnPAs than CNAs, but caution is needed in concluding that CNAs are more culturally-appropriate for assessing cognitive decline in older CALD individuals. Our findings extend current literature by confirming the influence of linguistic and acculturation variables on cognitive assessment outcomes for older CALD Australians.

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 P 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.

Diffusion weighted imaging (DWI) is a widely recognized neuroimaging technique to evaluate the microstructure of brain white matter. The objective of this study is to establish an improved automated DWI marker for estimating white matter integrity and investigating ageing related cognitive decline. The concept of Wasserstein distance was introduced to help establish a new measure: difference in distribution functions (DDF), which captures the difference of reshaping one's mean diffusivity (MD) distribution to a reference MD distribution. This new DWI measure was developed using a population-based cohort (n=19,369) from the UK Biobank. Validation was conducted using the data drawn from two independent cohorts: the Sydney Memory and Ageing Study, a community-dwelling sample (n=402), and the Renji Cerebral Small Vessel Disease Cohort Study (RCCS), which consisted of cerebral small vessel disease (CSVD) patients (n=171) and cognitively normal controls (NC) (n=43). DDF was associated with age across all three samples and better explained the variance of changes than other established DWI measures, such as fractional anisotropy, mean diffusivity and peak width of skeletonized mean diffusivity (PSMD). Significant correlations between DDF and cognition were found in the UK Biobank cohort and the MAS cohort. Binary logistic analysis and receiver operator characteristic curve analysis of RCCS demonstrated that DDF had higher sensitivity in distinguishing CSVD patients from NC than the other DWI measures. To demonstrate the flexibility of DDF, we calculated regional DDF which also showed significant correlation with age and cognition. DDF can be used as a marker for monitoring the white matter microstructural changes and ageing related cognitive decline in the elderly.

Objective: To synthesise international findings on the alcohol-dementia relationship and provide a cross-national comparison of the alcohol-dementia relationship with critical evidence for the relationship between alcohol use and dementia in under-studied populations. Design and setting: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in five continents. Cox regression investigated the dementia risk associated with alcohol use. Sensitivity analyses compared lifetime abstainers with former drinkers, adjusted extensively for demographic and clinical characteristics, and assessed the competing risk of death. Participants: 24,472 community-dwelling individuals without a history of dementia at baseline and at least one follow-up dementia assessment. Main outcome measure: All-cause dementia as determined by clinical interview. Results: During 151,574 person-years of follow-up, there were 2,137 incident cases of dementia (14.1 per 1,000 person-years). In the combined sample, when compared with occasional drinkers (

Background There is widespread consumer concern that statin use may be associated with impaired memory and cognitive decline. Objectives This study sought to examine the association between statin use and changes in memory and global cognition in the elderly population over 6 years and brain volumes over 2 years. Interactions between statin use and known dementia risk factors were examined. Methods Prospective observational study of community-dwelling elderly Australians age 70 to 90 years (the MAS [Sydney Memory and Ageing Study], n = 1,037). Outcome measures were memory and global cognition (by neuropsychological testing every 2 years) and total brain, hippocampal and parahippocampal volumes (by magnetic resonance) in a subgroup (n = 526). Analyses applied linear mixed modeling, including the covariates of age, sex, education, body mass index, heart disease, diabetes, hypertension, stroke, smoking, and apolipoprotein Ee4 carriage. Interactions were sought between statin use and dementia risk factors. Results Over 6 years there was no difference in the rate of decline in memory or global cognition between statin users and never users. Statin initiation during the observation period was associated with blunting the rate of memory decline. Exploratory analyses found statin use was associated with attenuated decline in specific memory test performance in participants with heart disease and apolipoprotein Ee4 carriage. There was no difference in brain volume changes between statin users and never users. Conclusions In community-dwelling elderly Australians, statin therapy was not associated with any greater decline in memory or cognition over 6 years. These data are reassuring for consumers concerned about statin use and risk of memory decline.

Background Hypertension is an established risk factor for stroke and vascular dementia but recent meta-analyses examining the association between Alzheimer's disease (AD) and hypertension have found no significant association. These meta-analyses included short term studies starting in late life which may have obscured the real effect of midlife hypertension. Objective To examine the association of AD with midlife hypertension, by including only studies with a sufficiently long follow up duration. Methods Relevant studies were found by searches of MEDLINE, EMBASE, and PubMed. Study outcomes were grouped by measures of blood pressure and definition of hypertension (e.g., systolic hypertension > 140 mmHg or > 160 mmHg). We assessed pooled effect estimates using random effects models and heterogeneity of pooled estimates through the I2 statistic. Results Literature search found 3,426 publications of which 7 were eligible studies. There was a significant association between systolic hypertension (>160 mm Hg) and AD (HR 1.25, 95CI 1.06 - 1.47, p = 0.0065). Similarly, for systolic hypertension > 140 mm Hg, there was a smaller but still significant association (HR 1.18, 95CI 1.02 - 1.35, p = 0.021). For diastolic hypertension, all four studies found no significant associations between diastolic hypertension and AD, and these data could not be pooled due to heterogeneity in reporting. Conclusions Our study found that midlife stage 1 and stage 2 systolic hypertension is associated with increased risk of AD by 18 and 25%, respectively, although no association was found for diastolic hypertension. It is likely that assertive control of systolic hypertension starting in midlife is important to preventing AD.

Objectives Telephone-based cognitive screens, such as the Telephone Interview for Cognitive Status (TICS), can potentially reduce the barriers and costs of assessing older adults. However, validation of clinically relevant psychometric properties is lacking in a large and comprehensively assessed sample of older adults. Furthermore, published normative data may lack sensitivity as they have not used regression-based demographic corrections or accounted for cases with subsequent dementia. We address these gaps using the modified TICS (TICS-M; a modified, 13-item, 39-point version) and provide an online norms calculator for clinicians and researchers. Design Prospective longitudinal study. Setting Sydney, Australia. Participants A total of 617 community-living older adults, aged from 71 to 91 years. Measurements The measures used included the TICS-M, the Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination-Revised (ACE-R), and a comprehensive neuropsychological test battery. Descriptive statistics, correlations, area under the curve, and regression analyses were used to determine the validity and normative properties of the TICS-M. Results TICS-M total scores (mean = 24.20; SD = 3.76) correlated well with the MMSE (0.70) and ACE-R (0.80) and moderately with neuropsychological tests tested noncontemporaneously. A cutoff score of 21 or lower reliably distinguished between those with and without incident dementia after 1 year (sensitivity = 77%; specificity = 88%) but was less reliable at distinguishing mild cognitive impairment from normal cognition. TICS-M scores decreased with age and increased with higher education levels. The robust normative sample, which excluded incident dementia cases, scored higher on the TICS-M and with less variability than the whole sample. An online calculator is provided to compute regression-based norms and reliable change statistics. Conclusions In a large sample of community-dwelling older adults, the TICS-M performed well in terms of construct validity against typical screening tools and neuropsychological measures and diagnostic validity for incident dementia. The comprehensive, regression-based, and robust normative data provided will help improve the sensitivity, accessibility, and cost-effectiveness of cognitive testing with older adults. J Am Geriatr Soc 67:2108-2115, 2019.

Background and purpose The Vascular Behavioral and Cognitive Disorders (VASCOG) criteria for vascular cognitive disorders were published in 2014, but their concurrent and predictive validity have not been examined. Methods Participants (N = 165, aged 49-86 years) were from Sydney Stroke Study, a longitudinal study of post-stroke cognitive impairment and dementia. Diagnoses using the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), the Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for vascular dementia (VaD) were made by consensus at multidisciplinary case conferences. Diagnoses for mild vascular cognitive disorder (mVCD) and VaD using VASCOG, DSM-5 and the Vascular Impairment of Cognition Classification Consensus Study (VICCCS) criteria were made by two study authors. Agreement levels between criteria sets were examined using Cohen's kappa (κ). The ability of VaD diagnoses to predict mortality over 10 years and of mVCD to predict dementia over 5 years was investigated. Results The VASCOG criteria yielded rates of mVCD slightly lower than for DSM-5 and VICCCS. VaD rates were similar for all criteria, although slightly lower for DSM-IV. Agreement between the VASCOG, VICCCS and DSM-5 criteria was excellent for VaD and mVCD (κ = 0.83-1.0), but lower for VaD between VASCOG and the other criteria (κ = 0.47-0.63). VaD-based mortality predictions were similar for the VASCOG, VICCCS and DSM-5 criteria, and higher than those for other criteria. The prediction of incident dementia within 5 years from mVCD was slightly lower with VASCOG criteria than with DSM-5 and VICCCS criteria. Conclusions The VASCOG criteria have greater sensitivity, modest concurrent validity and better predictive validity than older criteria for VaD, but are comparable to DSM-5 and VICCCS criteria. Their operationalization and inclusion of a mild VCD category make them useful for clinical and research applications.

Objective: While near-centenarians (95–99) and centenarians are the fastest growing sectors of the population in many countries, few studies have investigated their psychological health. We aimed to compare levels of psychological distress and life satisfaction in individuals aged 95 or above (95+) with younger age groups and identify the factors associated with psychological distress and life satisfaction in near-centenarians and centenarians. Methods: We assessed the physical, cognitive, social and psychological health of 207 participants aged 95+ in the Sydney Centenarian Study. Psychological distress and life satisfaction were rated on the Kessler Psychological Distress Scale (K10) and Satisfaction with Life Scale, respectively. Cross-sectional univariate comparisons were performed with participants aged 70–90 years from the Sydney Memory and Ageing Study. Factors associated with psychological distress and life satisfaction among Sydney Centenarian Study participants were examined using multiple regression analyses. Results: In Sydney Centenarian Study and Memory and Ageing Study, mean K10 scores were 15.3 (±5.9) and 13.4 (±3.6), and clinical levels of psychological distress (K10 ⩾ 20) were 19% and 7%, respectively. Sydney Centenarian Study participants demonstrated significantly higher levels and rates of psychological distress ( t = 3.869, p 2 = 27.331, p Conclusion: Despite showing higher levels of psychological distress in the prior 4 weeks than younger age groups, near-centenarians and centenarians remained highly satisfied with their overall lives. The identification of risk and protective factors for psychological distress and life satisfaction provides opportunities for interventions to maintain good psychological health in this vulnerable population.

ObjectiveTo determine whether severe perivascular space (PVS) dilation is associated with longitudinal cognitive decline and incident dementia over 4 and 8 years, respectively, we analyzed data from a prospective cohort study.MethodsA total of 414 community-dwelling older adults aged 72–92 years were assessed at baseline and biennially for up to 8 years, with cognitive assessments, consensus dementia diagnoses, and 3T MRI. The numbers of PVS in 2 representative slices in the basal ganglia (BG) and centrum semiovale (CSO) were counted and severe PVS pathology defined as the top quartile. The effects of severe PVS pathology in either region or both regions and those with severe BG PVS and severe CSO PVS were examined. White matter hyperintensity volume, cerebral microbleed number, and lacune number were calculated.ResultsParticipants with severe PVS pathology in both regions or in the CSO alone had greater decline in global cognition over 4 years, even after adjustment for the presence of other small vessel disease neuroimaging markers. The presence of severe PVS pathology in both regions was an independent predictor of dementia across 8 years (odds ratio 2.91, 95% confidence interval 1.43–5.95, p = 0.003). The presence of severe PVS pathology in all groups examined was associated with greater dementia risk at either year 4 or 6.ConclusionsSevere PVS pathology is a marker for increased risk of cognitive decline and dementia, independent of other small vessel disease markers. The differential cognitive associations for BG and CSO PVS may represent differences in their underlying pathology.

Background Subjective cognitive complaints (SCCs) are a risk factor for dementia; however, little is known about their trajectories. Method Participants were 873 older adults (mage = 78.65 years; 55% females) from the Sydney Memory and Ageing Study that were followed-up biennially. SCCs were measured using the six-item Memory Complaint Questionnaire. Associations between initial level of SCC reporting, linear change in SCC reporting, and change in global cognition over 6 years was examined using latent growth curve analysis. Risk of dementia was examined over 10 years using Cox regression. Results After controlling for demographics, mood and personality, results revealed a negative longitudinal association between the slope of SCCs and the slope of global cognition scores (b = -0.01, p = 0.005, β = -0.44), such that participants who reported increasing SCCs showed a steeper rate of decline in global cognition over 6 years. Cox regression also revealed participants who reported increasing SCCs had a nearly fourfold increased risk of developing dementia over 10 years (hazard ratio 3.70, 1.24-11.01). Conclusion This study explored whether initial levels of, and change in, SCCs over time are associated with both cognitive decline and risk of dementia. These findings are clinically relevant as GPs should note patients reporting increasing SCCs as they may be at greater risk of cognitive decline and incident dementia.

International audience; Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

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.