Promoting the Secondary Use of Clinical Research Data in Australia.

The research community in Australia is building a national infrastructure to facilitate access to and sharing of data from health studies. A federation of nine nodes representing 72 health research organisations provides coordination across their partners to establish systems, processes and relationships promoting FAIR approaches to clinical trial data. This paper describes this initiative.

Lifespace metrics of older adults with mild cognitive impairment and dementia recorded via geolocation data.

OBJECTIVE: Lifespace, the physical area in which someone conducts life activities, indicates lived community mobility. This study explored the feasibility of technology-based lifespace measurement for older people with dementia and mild cognitive impairment (MCI), including the generation of a range of lifespace metrics, and investigation of relationships with health and mobility status. METHODS: An exploratory study was conducted within a longitudinal observational study. Eighteen older adults (mean age 86.7 years (SD: 3.2); 8 men; 15 MCI), participated. Lifespace metrics were generated from geolocation data (GPS and Bluetooth beacon) collected through a smartphone application for one week (2015-2016). Cognitive and mobility-related outcomes were compared from study data sets at baseline (2005-2007) and 6-year follow-up (2011-2014). RESULTS: Lifespace data could be collected from all participants, and metrics were generated including percentage of time at home, maximum distance from home, episodes of travel in a week, days in a week participants left home, lifespace area (daily, weekly and total), indoor lifespace (regions in the home/hour), and a developed lifespace score that combined time, frequency of travel, distance and area. Results indicated a large range of lifespace areas (0.1 - 97.88 km2 ; median 6.77 km2 ) with similar patterns across lifespace metrics. Significant relationships were found between lifespace metrics and concurrent driving status and anteceding scores on the sit-to-stand test (at baseline and follow-up). CONCLUSIONS: Further longitudinal exploration of lifespace is required to develop an understanding of the nature of lifespace of older community-dwelling people, and its relationship with health, mobility and well-being outcomes.

Personalised predictive modelling with brain-inspired spiking neural networks of longitudinal MRI neuroimaging data and the case study of dementia.

BACKGROUND: Longitudinal neuroimaging provides spatiotemporal brain data (STBD) measurement that can be utilised to understand dynamic changes in brain structure and/or function underpinning cognitive activities. Making sense of such highly interactive information is challenging, given that the features manifest intricate temporal, causal relations between the spatially distributed neural sources in the brain. METHODS: The current paper argues for the advancement of deep learning algorithms in brain-inspired spiking neural networks (SNN), capable of modelling structural data across time (longitudinal measurement) and space (anatomical components). The paper proposes a methodology and a computational architecture based on SNN for building personalised predictive models from longitudinal brain data to accurately detect, understand, and predict the dynamics of an individual's functional brain state. The methodology includes finding clusters of similar data to each individual, data interpolation, deep learning in a 3-dimensional brain-template structured SNN model, classification and prediction of individual outcome, visualisation of structural brain changes related to the predicted outcomes, interpretation of results, and individual and group predictive marker discovery. RESULTS: To demonstrate the functionality of the proposed methodology, the paper presents experimental results on a longitudinal magnetic resonance imaging (MRI) dataset derived from 175 older adults of the internationally recognised community-based cohort Sydney Memory and Ageing Study (MAS) spanning 6 years of follow-up. SIGNIFICANCE: The models were able to accurately classify and predict 2 years ahead of cognitive decline, such as mild cognitive impairment (MCI) and dementia with 95% and 91% accuracy, respectively. The proposed methodology also offers a 3-dimensional visualisation of the MRI models reflecting the dynamic patterns of regional changes in white matter hyperintensity (WMH) and brain volume over 6 years. CONCLUSION: The method is efficient for personalised predictive modelling on a wide range of neuroimaging longitudinal data, including also demographic, genetic, and clinical data. As a case study, it resulted in finding predictive markers for MCI and dementia as dynamic brain patterns using MRI data.

New avenue for the geriatric depression scale: Rasch transformation enhances reliability of assessment.

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.

Validation and Normative Data for the Modified Telephone Interview for Cognitive Status: The Sydney Memory and Ageing Study.

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.

Operationalizing the Diagnostic Criteria for Mild Cognitive Impairment: The Salience of Objective Measures in Predicting Incident Dementia.

OBJECTIVE: Mild cognitive impairment (MCI) is considered an intermediate stage between normal aging and dementia. It is diagnosed in the presence of subjective cognitive decline and objective cognitive impairment without significant functional impairment, although there are no standard operationalizations for each of these criteria. The objective of this study is to determine which operationalization of the MCI criteria is most accurate at predicting dementia. DESIGN: Six-year longitudinal study, part of the Sydney Memory and Ageing Study. SETTING: Community-based. PARTICIPANTS: 873 community-dwelling dementia-free adults between 70 and 90 years of age. Persons from a non-English speaking background were excluded. MEASUREMENTS: Seven different operationalizations for subjective cognitive decline and eight measures of objective cognitive impairment (resulting in 56 different MCI operational algorithms) were applied. The accuracy of each algorithm to predict progression to dementia over 6 years was examined for 618 individuals. RESULTS: Baseline MCI prevalence varied between 0.4% and 30.2% and dementia conversion between 15.9% and 61.9% across different algorithms. The predictive accuracy for progression to dementia was poor. The highest accuracy was achieved based on objective cognitive impairment alone. Inclusion of subjective cognitive decline or mild functional impairment did not improve dementia prediction accuracy. CONCLUSIONS: Not MCI, but objective cognitive impairment alone, is the best predictor for progression to dementia in a community sample. Nevertheless, clinical assessment procedures need to be refined to improve the identification of pre-dementia individuals.

The relationship between inflammatory markers and voxel-based gray matter volumes in nondemented older adults.

Ageing is characterized by chronically elevated inflammatory markers (IMs). Peripheral IM levels have been found in negative correlations with brain structural measures including global and lobar volumes and the hippocampus. This study investigated the relationship between 10 peripheral IMs and voxel-based gray matter (GM) volumes in nondemented older adults (n = 463). Two proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-1ß) and 2 vascular IMs (vascular cellular adhesion molecule-1 and plasminogen activator inhibitor-1) were negatively correlated with regional GM volumes. TNF-α and interleukin-1ß were both significantly correlated with GM volumes in the left occipitotemporal area, left superior occipital gyrus, and left inferior parietal lobule; TNF-α was also significantly correlated with the bilateral medial prefrontal cortices and approached significance for the correlations with the bilateral hippocampi. Significant GM correlations with vascular cellular adhesion molecule-1 were located in the bilateral anterior cingulate cortices, and with plasminogen activator inhibitor-1 in the cerebellum and right hippocampus. The neuroanatomical correlation patterns of 2 proinflammatory cytokines and 2 vascular IMs might be reflective of the effects of neurodegenerative and vascular pathological processes in the ageing brain.

Correlates of psychological distress in study partners of older people with and without mild cognitive impairment (MCI) - the Sydney Memory and Ageing Study.

OBJECTIVES: Psychological effects of supporting someone with mild cognitive impairment (MCI) are often overlooked. We aimed to establish correlates of psychological distress in study partners of individuals with and without nonclinical MCI. METHODS: Demographic, psychosocial and health measures were obtained cross-sectionally from 714 participants (39% MCI) and study partners of a longitudinal community-based study on cognitive aging. Study partners (i.e. family members/friends) were categorized as providing support with instrumental everyday activities or not. Psychological distress was measured by the Kessler psychological distress scale. Multiple hierarchical regressions examined determinants of psychological distress within Pearlin's stress process model. RESULTS: Psychological distress was generally low and not associated with MCI or whether study partners provided support or not. Instead, distress was greater if participants were male irrespective of study partners' sex and if study partners reported negative reactions to participants' behavioral symptoms, felt burdened by providing support and showed worse coping abilities; overall explaining 37% variance. Self-rated disability and aspects of health-related quality of life explained additional 7%. CONCLUSION: Objective impairment measures were not associated with distress in partners or supporters. However, study partners' appraisals of functional and behavioral symptoms were linked to increased distress even in this very mildly affected community cohort.

Grey matter correlates of three language tests in non-demented older adults.

Language has been extensively investigated by functional neuroimaging studies. However, only a limited number of structural neuroimaging studies have examined the relationship between language performance and brain structure in healthy adults, and the number is even less in older adults. The present study sought to investigate correlations between grey matter volumes and three standardized language tests in late life. The participants were 344 non-demented, community-dwelling adults aged 70-90 years, who were drawn from the population-based Sydney Memory and Ageing Study. The three language tests included the Controlled Oral Word Association Task (COWAT), Category Fluency (CF), and Boston Naming Test (BNT). Correlation analyses between voxel-wise GM volumes and language tests showed distinctive GM correlation patterns for each language test. The GM correlates were located in the right frontal and left temporal lobes for COWAT, in the left frontal and temporal lobes for CF, and in bilateral temporal lobes for BNT. Our findings largely corresponded to the neural substrates of language tasks revealed in fMRI studies, and we also observed a less hemispheric asymmetry in the GM correlates of the language tests. Furthermore, we divided the participants into two age groups (70-79 and 80-90 years old), and then examined the correlations between structural laterality indices and language performance for each group. A trend toward significant difference in the correlations was found between the two age groups, with stronger correlations in the group of 70-79 years old than those in the group of 80-90 years old. This difference might suggest a further decline of language lateralization in different stages of late life.

Risk factors for late-life cognitive decline and variation with age and sex in the Sydney Memory and Ageing Study.

INTRODUCTION: An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline. METHODS: Participants were 889 community-dwelling 70-90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined. RESULTS: All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7-49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine. DISCUSSION: Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits.

Factors predicting reversion from mild cognitive impairment to normal cognitive functioning: a population-based study.

INTRODUCTION: Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition. METHODS: Our analyses considered 223 participants (48.9% male) aged 71-89 years, drawn from the prospective, population-based Sydney Memory and Ageing Study. All were diagnosed with MCI at baseline and subsequently classified with either normal cognition or repeat diagnosis of MCI after two years (a further 11 participants who progressed from MCI to dementia were excluded). Associations with reversion were investigated for (1) baseline factors that included diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and physical and mental health; (2) longitudinal change in potentially modifiable factors. RESULTS: There were 66 reverters to normal cognition and 157 non-reverters (stable MCI). Regression analyses identified diagnostic features as most predictive of prognosis, with reversion less likely in participants with multiple-domain MCI (p = 0.011), a moderately or severely impaired cognitive domain (p = 0.002 and p = 0.006), or an informant-based memory complaint (p = 0.031). Reversion was also less likely for participants with arthritis (p = 0.037), but more likely for participants with higher complex mental activity (p = 0.003), greater openness to experience (p = 0.041), better vision (p = 0.014), better smelling ability (p = 0.040), or larger combined volume of the left hippocampus and left amygdala (p<0.040). Reversion was also associated with a larger drop in diastolic blood pressure between baseline and follow-up (p = 0.026). DISCUSSION: Numerous factors are associated with reversion from MCI to normal cognition. Assessing these factors could facilitate more accurate prognosis of individuals with MCI. Participation in cognitively enriching activities and efforts to lower blood pressure might promote reversion.

The Sydney Centenarian Study: methodology and profile of centenarians and near-centenarians.

BACKGROUND: The study of exceptionally long-living individuals can inform us about the determinants of successful aging. There are few population-based studies of centenarians and near-centenarians internationally, but none in Australia. METHODS: Individuals 95 years and older were recruited from seven electoral districts in Sydney using the electoral roll, Medicare lists, and multiple other strategies to obtain a representative sample. Physical and mental health and cognitive status were assessed using standard instruments in multiple sessions, with assessments individually adapted. An informant was interviewed, and participants were invited to donate a blood sample, undergo an MRI scan, and enrol into the brain donation program. RESULTS: Preliminary data on the first 200 participants are reported. Mean age was 97.4 years (range 95-106), with 29.5% being men, and 58.5% living in a private dwelling. Rates of heart disease and diabetes were lower than in octogenarians, but hearing and visual deficits were common. The mean mini-mental state examination (MMSE) score was 21.1, with men performing better. Rates of psychological distress were low and satisfaction with life high (mean 5.91 out of a maximum of 7); 54% scored <24 on MMSE; 39.5% were impaired on both MMSE and a functional measure; and 20% had previous diagnosis of dementia. CONCLUSIONS: This is a preliminary report describing the methodology of the study. It provides further evidence that dementia is not inevitable at this age and independent living is common. The study provides an excellent resource to determine the genetic and environmental contributions to long and successful cognitive aging.

Sydney Memory and Ageing Study: an epidemiological cohort study of brain ageing and dementia.

Non-demented community-dwelling older adults aged 70-90 years (n = 1,037) randomly recruited from the electoral roll completed neuropsychological and medical assessments over six years. The overall prevalence of mild cognitive impairment (MCI) at baseline was 36.7%. Risk factors for MCI include APOE ε4 allele carrier status, high homocysteine, heart disease, poor odour identification, low visual acuity and low mental activity, but notable age and sex differences were observed. Neuropsychiatric symptoms were rare; depression was the most common and was associated with cognitive impairment in at least one domain as well as subsequent dementia 2 years later. Poorer cognitively demanding functional abilities were associated with cognitive impairment. Biomarkers for cognitive impairment and decline were identified. Inflammatory markers and plasma apolipoprotein levels were associated with poorer performance in the attention/processing speed domain. Measures of white matter lesions, white matter integrity, sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline. Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline. Compared to previous reports, our prevalence rates of MCI were higher but rates of progression to dementia and reversion to normal were similar, as were risk factors for progression to dementia.

The contribution of twins to the study of cognitive ageing and dementia: the Older Australian Twins Study.

The Older Australian Twins Study (OATS) is a major longitudinal study of twins, aged ≥ 65 years, to investigate genetic and environmental factors and their interactions in healthy brain ageing and neurocognitive disorders. The study collects psychiatric, neuropsychological, cardiovascular, metabolic, biochemical, neuroimaging, genomic and proteomic data, with two-yearly assessments, and is currently in its third wave. The initial cohort comprises 623 individuals (161 monozygotic and 124 dizygotic twin pairs; 1 MZ triplets; 27 single twins and 23 non-twin siblings), of whom 426 have had wave 2 assessment. A number of salient findings have emerged thus far which assist in the understanding of genetic contributions to cognitive functions such as processing speed, executive ability and episodic memory, and which support the brain reserve hypothesis. The heritability of brain structures, both cortical and subcortical, brain spectroscopic metabolites and markers of small vessel disease, such as lacunar infarction and white matter hyperintensities, have been examined and can inform future genetic investigations. Work on amyloid imaging and functional magnetic resonance imaging is proceeding and epigenetic studies are progressing. This internationally important study has the potential to inform research into cognitive ageing in the future, and offers an excellent resource for collaborative work.

Risk profiles for mild cognitive impairment vary by age and sex: the Sydney Memory and Ageing study.

OBJECTIVES: : To examine age- and sex-related differences in risk and protective factors for mild cognitive impairment (MCI) in community-based elderly individuals. DESIGN: : Cross-sectional study. SETTING: : The population-based Sydney Memory and Ageing Study. PARTICIPANTS: : A total of 757 nondemented, community-dwelling elderly individuals from an English-speaking background categorized as younger (70-79 years) or older (80-90 years). MEASUREMENTS: : Risk of MCI was determined for sociodemographic, lifestyle, and cardiac, physical, mental, and general health factors using age- (and sex-) adjusted multiple regressions comprising initially significant univariate factors. RESULTS: : The point prevalence of MCI within our sample was 39.1% overall: it was lowest in younger women (32.3%) and similar across men and older women (41.9%-43.6%). The risk of MCI across all participants was increased by the APOE ∊4 allele, high homocysteine, and heart disease; and decreased by better odor identification, visual acuity, and mental activity. Risk factors in all younger participants were slow 6-m walk, poor odor identification, and high homocysteine. Risk of MCI was associated in younger women with history of depression, less mental activity, slower 6-m walk, poorer visual acuity, and higher homocysteine; and in younger men with poorer odor identification and higher homocysteine. Older participants showed no significant risk factors for MCI, except for poorer visual acuity in men. Supporting these findings were statistically significant interactions that reflected the differences in risk factor profiles between age and/or sex groups. CONCLUSIONS: : Risk factors for MCI differ in men and women and vary with age. This has implications for preventing MCI and possibly dementia.

Gray matter atrophy patterns of mild cognitive impairment subtypes.

Mild cognitive impairment (MCI) is a heterogeneous neurocognitive disorder that can be classified into various subtypes. The present study aims to examine the gray matter (GM) atrophy patterns of MCI subtypes in comparison with a cognitively healthy group. Participants, including 135 MCI subjects and 120 cognitively healthy controls, were drawn from the Sydney Memory and Ageing Study. The MCI subjects were first categorized into amnestic (aMCI) and non-amnestic (naMCI) subtypes, which were then divided into single-domain (aMCI-SD and naMCI-SD) and multiple-domain subtypes (aMCI-MD and naMCI-MD). Furthermore, naMCI-SD was divided into three subgroups (language, processing speed, and executive function) according to individual cognitive impairment. Voxel-wise GM volumes were then compared between MCI subtypes and controls. The aMCI group had significantly lower GM volumes in the bilateral hippocampi and temporal cortices than the controls. This was mainly due to GM reduction of aMCI-MD but not aMCI-SD, as the latter did not show any significant GM reduction. GM reduction of naMCI and its two subdivisions was shown in widespread brain regions compared to controls. GM volumes of the multiple-domain subtypes (aMCI-MD and naMCI-MD) were lower than their single-domain counterparts (aMCI-SD and naMCI-SD) in the frontal and temporal lobes, respectively. Moreover, the language subgroup of naMCI-SD showed GM reduction in the frontal and temporal lobes compared to controls. MCI subtypes displayed specific patterns of GM atrophy that appear to be related to their various clinical presentations, which implies that underlying mechanisms of MCI subtypes are different.

Risk profiles of subtypes of mild cognitive impairment: the sydney memory and ageing study.

OBJECTIVES: To compare the risk profiles of mild cognitive impairment (MCI) subtypes in a population-based elderly sample. DESIGN: Cross-sectional study. SETTING: The population-based Sydney Memory and Ageing Study. PARTICIPANTS: Seven hundred fifty-seven English-speaking, community-dwelling individuals without dementia aged 70 to 90. MEASUREMENTS: Comprehensive neuropsychological assessments were used to diagnose MCI and its subtypes, categorized as amnestic (aMCI) or nonamnestic (naMCI) and as single- (sdMCI) or multiple- (mdMCI) domain. Risk profiles were derived from sociodemographic; lifestyle; and cardiac, physical, mental, and general health data. Whole-sample and sex-specific comparisons between aMCI and naMCI and between mdMCI and sdMCI were made using age- (and sex-) adjusted multiple regressions comprising initially significant univariate factors. RESULTS: Risk factors for MCI were presence of the apolipoprotein E (APOE) ε4 allele, heart disease, high homocysteine, poor odor identification ability, low visual acuity, and lower mental activity. The odds of having naMCI rather than aMCI were lower with greater levels of social activity and greater if taking antihypertensives, the latter particularly in men. The odds of naMCI were greater in men taking antidepressants or with a longer 6-meter walk time and in women with hypertension. The odds of having mdMCI rather than sdMCI were greater in participants with a history of depression or having the APOE ε4 allele. Greater odds of mdMCI were also associated with lower mental activity, particularly for women. For men, the odds of mdMCI were greater with the APOE ε4 allele and lower if diagnosed with high cholesterol. CONCLUSION: MCI subtypes exhibit distinctive, sex-dependent risk profiles. This is consistent with MCI subtypes having different etiologies and outcomes and supports the idea that subtyping MCI may offer predictive validity and clinical application.

Neuroanatomical correlates of cognitive performance in late life.

BACKGROUND/AIM: While a number of studies examined the neuroanatomical correlates of cognitive function in older adults, the results have been inconsistent. Examination of a large epidemiologically acquired sample with high-resolution magnetic resonance imaging has the potential to enhance the evidence in this field. METHODS: The participants were 326 non-demented elderly adults undergoing a battery of neuropsychological tests and brain magnetic resonance imaging scans. Regression analyses were performed to examine the correlation between voxel-based grey matter (GM) volume and four cognitive domain scores. RESULTS: Positive correlations were observed between specific GM volumes and cognitive domains, i.e. bilateral temporal lobes and hippocampi with language; bilateral temporal, parietal, and occipital lobes with processing speed; and bilateral frontal, temporal, parietal, and occipital lobes with executive function. The positive correlation between verbal memory performance and GM volume in the bilateral medial temporal lobes was not significant after correction for age. CONCLUSION: Our findings suggest that the location of GM correlates of cognitive tests is largely consistent with the conventional understanding of the neuroanatomical basis of cognition. However, the lack of hemispheric predominance in these GM correlates, and the extensively positive correlation between GM volume and cognitive performance, perhaps reflects the characteristics of the ageing brain.

The relationship of neuropsychological function to instrumental activities of daily living in mild cognitive impairment.

OBJECTIVE: While activities of daily living are by definition preserved in mild cognitive impairment (MCI), there is evidence of poorer instrumental activities of daily living (IADL) functioning in MCI compared to normal ageing. The aims of the present study were to examine differences in IADL between individuals with MCI and cognitively normal elderly, and to examine the relationships of IADL with cognitive functions. METHODS: The sample of 762 community-living participants aged 70-90 were assessed with a comprehensive neuropsychological test battery and with the informant-completed Bayer-Activities of Daily Living Scale (B-ADL). RESULTS: Compared to cognitively normal individuals, the MCI group was rated as having more difficulties on the B-ADL and performed worse on cognitive tests. Factor analysis of the B-ADL items yielded two factors, which were labelled 'high cognitive demand' (HCD) and 'low cognitive demand' (LCD). Individuals with MCI scored worse than cognitively normal participants on the HCD factor but similarly on the LCD factor. Men were rated as having more difficulties on the HCD, but not the LCD, factor compared to women. The HCD factor score correlated significantly with all five cognitive domains measured, but the LCD factor correlated significantly only with attention/processing speed and to a lesser extent with executive function. CONCLUSIONS: Having more difficulties in IADL, especially those with higher demand on cognitive capacities, was found to be associated with MCI and overall cognitive functioning. This has implications for the definition of MCI, as lack of functional impairment is generally used as a criterion for diagnosis.

Grey matter atrophy of basal forebrain and hippocampus in mild cognitive impairment.

The basal forebrain area (BFA) is closely connected to the hippocampus by virtue of cholinergic neuronal projections. Structural neuroimaging studies have shown reduced volumes of both structures in Alzheimer's disease and its prodromal stage mild cognitive impairment (MCI), but generally not in the same investigation. By combining voxel based morphometry and region of interest methods, we measured the grey matter (GM) volumes of the two brain regions with the goal of elucidating their contributions to MCI and its two subtypes (amnestic MCI and non-amnestic MCI) in an elderly epidemiological sample. The results replicated previous findings that the atrophies of both brain regions were associated with an increased likelihood of MCI and its two subtypes. However, in a regression model for the prediction of MCI with GM volumes for both regions used as predictors, only hippocampal atrophy remained significant. Two possible interpretations for this pattern of results were discussed. One is that the observed correlation between BFA atrophy and MCI is spurious and due to the hippocampal atrophy correlated with both. Alternatively, our observation is consistent with the possibility that BFA atrophy has a causal effect on MCI, which is mediated via its influence on hippocampal atrophy. Furthermore, we found that the left hippocampal atrophy had a stronger effect than the right hippocampus and bilateral BFA in the prediction of amnestic MCI occurrence when the four unilateral areas were entered into one regression model. In addition, a slight but statistically significant difference was found in the left hippocampal volume between APOE ε4 allele carriers and non-carriers, consistent with prior studies.