Kristan Kang

The Sydney Memory and Ageing Study (MAS): methodology and baseline medical and neuropsychiatric characteristics of an elderly epidemiological non-demented cohort of Australians aged 70-90 years.

BACKGROUND The Sydney Memory and Ageing Study (Sydney MAS) was initiated in 2005 to examine the clinical characteristics and prevalence of mild cognitive impairment (MCI) and related syndromes, and to determine the rate of change in cognitive function over time. METHODS Non-demented community-dwelling individuals (N = 1037) aged 70-90 were recruited from two areas of Sydney, following a random approach to 8914 individuals on the electoral roll. They underwent detailed neuropsychiatric and medical assessments and donated a blood sample for clinical chemistry, proteomics and genomics. A knowledgeable informant was also interviewed. Structural MRI scans were performed on 554 individuals, and subgroups participated in studies of falls and balance, metabolic and inflammatory markers, functional MRI and prospective memory. The cohort is to be followed up with brief telephone reviews annually, and detailed assessments biannually. RESULTS This is a generally well-functioning cohort mostly living in private homes and rating their health as being better than average, although vascular risk factors are common. Most (95.5%) participants or their informants identified a cognitive difficulty, and 43.5% had impairment on at least one neuropsychological test. MCI criteria were met by 34.8%; with 19.3% qualifying for amnestic MCI, whereas 15.5% had non-amnestic MCI; 1.6% had impairment on neuropsychological test performance but no subjective complaints; and 5.8% could not be classified. The rate of MCI was 30.9% in the youngest (70-75) and 39.1% in the oldest (85-90) age bands. Rates of depression and anxiety were 7.1% and 6.9% respectively. CONCLUSIONS Cognitive complaints are common in the elderly, and nearly one in three meet criteria for MCI. Longitudinal follow-up of this cohort will delineate the progression of complaints and objective cognitive impairment, and the determinants of such change.

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

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.

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.

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

To compare the risk profiles of mild cognitive impairment (MCI) subtypes in a population‐based elderly sample.

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.

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.

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.

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 Alzheimers 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.

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.