The heritability of amyloid burden in older adults: the Older Australian Twins Study.

OBJECTIVE: To determine the proportional genetic contribution to the variability of cerebral ß-amyloid load in older adults using the classic twin design. METHODS: Participants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females; mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females; mean age: 71.14 (5.15) years) were drawn from the Older Australian Twins Study. Participants underwent detailed clinical and neuropsychological evaluations, as well as MRI, diffusion tensor imaging (DTI) and amyloid PET scans. Fifty-eight participants (17 MZ pairs, 12 DZ pairs) had PET scans with 11Carbon-Pittsburgh Compound B, and 148 participants (44 MZ pairs, 30 DZ pairs) with 18Fluorine-NAV4694. Cortical amyloid burden was quantified using the centiloid scale globally, as well as the standardised uptake value ratio (SUVR) globally and in specific brain regions. Small vessel disease (SVD) was quantified using total white matter hyperintensity volume on MRI, and peak width of skeletonised mean diffusivity on DTI. Heritability (h2) and genetic correlations were measured with structural equation modelling under the best fit model, controlling for age, sex, tracer and scanner. RESULTS: The heritability of global amyloid burden was moderate (0.41 using SUVR; 0.52 using the centiloid scale) and ranged from 0.20 to 0.54 across different brain regions. There were no significant genetic or environmental correlations between global amyloid burden and markers of SVD. CONCLUSION: Amyloid deposition, the hallmark early feature of Alzheimer's disease, is under moderate genetic influence, suggesting a major environmental contribution that may be amenable to intervention.

Can the Clinical Dementia Rating Scale Identify Mild Cognitive Impairment and Predict Cognitive and Functional Decline?

BACKGROUND: The Clinical Dementia Rating Scale (CDR) is used to rate dementia severity. Its utility in diagnosing mild cognitive impairment (MCI) and its predictive value remain unknown. AIMS: The aim of this study was to examine the association between CDR scores and expert MCI diagnosis, and to determine whether baseline CDR scores were predictive of cognitive or functional decline and progression to dementia over 6 years. METHODS: At baseline, the sample comprised 733 non-demented participants aged 70-90 years from the longitudinal Sydney Memory and Ageing Study. Global and sum of boxes CDR scores were obtained at baseline. Participants also received comprehensive neuropsychological and functional assessment as well as expert consensus diagnoses at baseline and follow-up. RESULTS: At baseline, CDR scores had high specificity but low sensitivity for broadly defined MCI. The balance of sensitivity and specificity improved for narrowly defined MCI. Longitudinally, all baseline CDR scores predicted functional change and dementia, but CDR scores were not predictive of cognitive change. CONCLUSION: CDR scores do not correspond well with MCI, except when MCI is narrowly defined, suggesting that the CDR taps into the more severe end of MCI. All CDR scores usefully predict functional decline and incident dementia.

ICC-dementia (International Centenarian Consortium - dementia): an international consortium to determine the prevalence and incidence of dementia in centenarians across diverse ethnoracial and sociocultural groups.

BACKGROUND: Considerable variability exists in international prevalence and incidence estimates of dementia. The accuracy of estimates of dementia in the oldest-old and the controversial question of whether dementia incidence and prevalence decline at very old age will be crucial for better understanding the dynamics between survival to extreme old age and the occurrence and risk for various types of dementia and comorbidities. International Centenarian Consortium - Dementia (ICC-Dementia) seeks to harmonise centenarian and near-centenarian studies internationally to describe the cognitive and functional profiles of exceptionally old individuals, and ascertain the trajectories of decline and thereby the age-standardised prevalence and incidence of dementia in this population. The primary goal of the ICC-Dementia is to establish a large and thorough heterogeneous sample that has the power to answer epidemiological questions that small, separate studies cannot. A secondary aim is to examine cohort-specific effects and differential survivorship into very old age. We hope to lay the foundation for further investigation into risk and protective factors for dementia and healthy exceptional brain ageing in centenarians across diverse ethnoracial and sociocultural groups. METHODS: Studies focusing on individuals aged ≥95 years (approximately the oldest 1 percentile for men, oldest 5th percentile for women), with a minimum sample of 80 individuals, including assessment of cognition and functional status, are invited to participate. There are currently seventeen member or potential member studies from Asia, Europe, the Americas, and Oceania. Initial attempts at harmonising key variables are in progress. DISCUSSION: General challenges facing large, international consortia like ICC-Dementia include timely and effective communication among member studies, ethical and practical issues relating to human subject studies and data sharing, and the challenges related to data harmonisation. A specific challenge for ICC-Dementia relates to the concept and definition of'abnormal' in this exceptional group of individuals who are rarely free of physical, sensory and/or cognitive impairments.

Predicting Cognitive, Functional, and Diagnostic Change over 4 Years Using Baseline Subjective Cognitive Complaints in the Sydney Memory and Ageing Study.

OBJECTIVE: There is limited understanding of the usefulness of subjective cognitive complaint(s) (SCC) in predicting longitudinal outcome because most studies focus solely on memory (as opposed to nonmemory cognitive) complaints, do not collect data from both participants and informants, do not control for relevant covariates, and have limited outcome measures. Therefore the authors investigate the usefulness of participant and informant SCCs in predicting change in cognition, functional abilities, and diagnostic classification of mild cognitive impairment or dementia in a community-dwelling sample over 4 years. METHODS: Nondemented participants (N = 620) in the Sydney Memory and Ageing Study aged between 70 and 90 years completed 15 memory and 9 nonmemory SCC questions. An informant completed a baseline questionnaire that included 15 memory and 4 nonmemory SCC questions relating to the participant. Neuropsychological, functional, and diagnostic assessments were carried out at baseline and again at 4-year follow-up. Cross-sectional and longitudinal analyses were carried out to determine the association between SCC indices and neuropsychological, functional, and diagnostic data while controlling for psychological measures. RESULTS: Once participant characteristics were controlled for, participant complaints were generally not predictive of cognitive or functional decline, although participant memory-specific complaints were predictive of diagnostic conversion. Informant-related memory questions were associated with global cognitive and functional decline and with diagnostic conversion over 4 years. CONCLUSION: Informant memory complaint questions were better than participant complaints in predicting cognitive and functional decline as well as diagnoses over 4 years.

White matter integrity and late-life depression in community-dwelling individuals: diffusion tensor imaging study using tract-based spatial statistics.

BACKGROUND: Late-life depression has been associated with white matter changes in studies using the regions of interest approach. AIMS: To investigate the cross-sectional and longitudinal relationship between white matter integrity and depression in community-dwelling individuals using diffusion tensor imaging with tract-based spatial statistics. METHOD: The sample comprised 381 participants aged between 72 and 92 years who were assessed twice within 2 years. Depressive symptoms were measured with the Geriatric Depression Scale. Tract-based spatial statistics were applied to investigate white matter integrity in currently depressed v. non-depressed elderly people and in those with a history of depression v. no history of depression. The relationship between white matter integrity and development of depressive symptoms after 2 years were analysed with logistic regression. RESULTS: Individuals with current depression had widespread white matter integrity reduction compared with non-depressed elderly people. Significant fractional anisotropy reductions were found in 45 brain areas with the most notable findings in the frontal lobe, association and projection fibres. A history of depression was not associated with reduced fractional anisotropy. White matter changes in the superior frontal gyrus, posterior thalamic radiation, superior longitudinal fasciculus and in the body of corpus callosum predicted depression at follow-up. CONCLUSIONS: Reduced white matter integrity is associated with late-life depression and predicts future depressive symptoms whereas a history of depression is not related to white matter changes. Disruption to white matter integrity may be a biomarker to predict late-life depression.

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.

A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease.

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.

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.

Mild cognitive impairment in a community sample: the Sydney Memory and Ageing Study.

BACKGROUND: Mild cognitive impairment (MCI) is associated with an increased dementia risk. This study reports incidence of MCI subtypes, rates of progression to dementia, and stability of MCI classification. METHODS: We examined 873 community-dwelling adults aged 70 to 90 years over 2 years as part of an ongoing population-based longitudinal study, the Sydney Memory and Ageing Study. Neuropsychological testing assessed five cognitive domains, and a diagnosis of no cognitive impairment, MCI, or dementia (follow-up only) was made according to published criteria. RESULTS: The incidence of MCI was 104.6 (95% confidence interval: 81.6-127.7) per 1000 person-years, with higher incidence in men (men, 156.8; women, 70.3). Incidence rates for single-domain amnestic, multiple-domain amnestic, single-domain nonamnestic, and multiple-domain nonamnestic MCI were 47.7, 7.9, 45.0, and 3.9 per 1000 person-years, respectively. The 2-year rate of progression from MCI at baseline to dementia was 4.8%, being highest for multidomain amnestic MCI (9.1%). Of those with MCI at baseline, 28.2% reverted to no cognitive impairment at follow-up. Sensitivity analyses by redefining criteria for cognitive impairment did not affect stability of diagnosis, although changing the threshold of domain impairment reduced baseline MCI prevalence from 36.7% to 5.7% and incidence to 23.5, and increased 2-year progression rate from MCI to dementia to 14.3%. CONCLUSIONS: Incidence rates for MCI are higher than previously reported, particularly in men and for single-domain MCI; rates for amnestic and nonamnestic MCI were comparable. Multidomain amnestic MCI was the most likely subtype to progress to dementia, but overall, the diagnosis of MCI, particularly single-domain MCI, shows considerable instability.

Discrete neuroanatomical networks are associated with specific cognitive abilities in old age.

There have been many attempts at explaining age-related cognitive decline on the basis of regional brain changes, with the usual but inconsistent findings being that smaller gray matter volumes in certain brain regions predict worse cognitive performance in specific domains. Additionally, compromised white matter integrity, as suggested by white matter hyperintensities or decreased regional white matter fractional anisotropy, has an adverse impact on cognitive functions. The human brain is, however, a network and it may be more appropriate to relate cognitive functions to properties of the network rather than specific brain regions. We report on graph theory-based analyses of diffusion tensor imaging tract-derived connectivity in a sample of 342 healthy individuals aged 72-92 years. The cognitive domains included processing speed, memory, language, visuospatial, and executive functions. We examined the association of these cognitive assessments with both the connectivity of the whole brain network and individual cortical regions. We found that the efficiency of the whole brain network of cortical fiber connections had an influence on processing speed and visuospatial and executive functions. Correlations between connectivity of specific regions and cognitive assessments were also observed, e.g., stronger connectivity in regions such as superior frontal gyrus and posterior cingulate cortex were associated with better executive function. Similar to the relationship between regional connectivity efficiency and age, greater processing speed was significantly correlated with better connectivity of nearly all the cortical regions. For the first time, regional anatomical connectivity maps related to processing speed and visuospatial and executive functions in the elderly are identified.

Can mild cognitive impairment be accurately diagnosed in english speakers from linguistic minorities? Results from the Sydney Memory and Ageing study.

OBJECTIVES: : The aim of this article was to examine the prevalence and incidence over 2 years of mild cognitive impairment (MCI) in English speakers from linguistic minorities. DESIGN: : Cross-sectional and longitudinal with 2-year follow-up. SETTING: : Eastern suburbs of Sydney, New South Wales, Australia. PARTICIPANTS: : Eight hundred twenty-seven community-dwelling participants from English-speaking backgrounds (ESB) and 160 participants from non-English-speaking backgrounds (NESB) recruited through the electoral roll. MEASUREMENTS: : Participants were assessed using 11 neuropsychological tests measuring memory, language, attention/processing speed, and executive function. Questionnaires measuring functional impairment and subjective cognitive complaints were completed by participants or informants. RESULTS: : We found a two- to threefold higher prevalence of MCI in NESB participants than ESB participants depending on the impairment criterion applied. This difference was because of higher rates of objective cognitive impairment in NESB participants; rates of functional impairment and subjective cognitive complaints did not differ between the groups. This association between MCI prevalence and NESB status was accounted for by the proportion of time the participant spoke English and the proportion of life they had lived in Australia, but not by age, gender, and education. There were no differences between NESB and ESB groups in MCI incidence, dementia incidence, or rates of conversion from MCI to dementia. NESB participants had lower rates of reversion from MCI to normal. CONCLUSIONS: : It is difficult to accurately diagnose MCI in persons from linguistic minority groups, even when proficient in English as neuropsychological test scores may not be valid for these groups. English language ability and level of acculturation should be considered when assessing older persons from ethnic minority groups.

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.

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.

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.

Prevalence and predictors of "subjective cognitive complaints" in the Sydney Memory and Ageing Study.

OBJECTIVES: To document the prevalence of self- and informant report of cognitive problems, usually referred to as "subjective cognitive complaints" (SCCs), in a community-dwelling sample of older adults and to examine the relationship between SCCs and objective impairment, mood, and personality measures. PARTICIPANTS: Eight hundred twenty-seven nondemented community-dwelling adults aged 70-90 years. MEASUREMENTS: Participants were asked 24 SCC questions, including the Memory Complaint Questionnaire (MAC-Q), and completed neuropsychological testing in the domains of memory, language, executive function, visuospatial skills, and psychomotor speed. The Geriatric Depression Scale, Goldberg Anxiety Scale, and Neuroticism, Openness, and Conscientiousness from the NEO-Five Factor Inventory were used as measures of participants' psychological status. Informants completed 19 SCC questions, including a modified short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: Overall, 95.5% of participants or their informants endorsed at least one SCC. Although participants were more likely to endorse a memory complaint, informants seemed more accurate in endorsing a complaint when cognitive impairment was objectively present. SCC correlated with participants' scores on measures of depression, anxiety, neuroticism, and inversely with measures of openness and conscientiousness. Age, education, and sex had little impact on these effects. Regression analysis showed that psychological factors explained the number of complaints more than cognitive performance. CONCLUSIONS: The usefulness of SCCs as a criterion for mild cognitive impairment is questioned because of their high prevalence and their relationship to psychological factors. This may be helpful for clinicians to bear in mind when presented with patients with cognitive complaints.

Effect of different impairment criteria on prevalence of "objective" mild cognitive impairment in a community sample.

OBJECTIVES: Objective cognitive impairment determined by neuropsychological test performance is a core criterion for the diagnosis of mild cognitive impairment (MCI), yet no consensus has been reached on how this criterion should be operationalized. The aims of this study were to investigate the effect of varying the criteria used to determine cognitive impairment (CI) on prevalence and case definition and to examine comparability of different criteria. DESIGN: Cross-sectional study. SETTING: Sydney Memory and Ageing Study, Australia. PARTICIPANTS: Nine hundred eighty-seven nondemented community-dwelling adults aged 70-90 years were enrolled in this study. MEASUREMENTS: Participants received a comprehensive neuropsychological test battery measuring four cognitive domains. They were classified as normal or cognitively impaired by applying two types of "impairment" rule that varied the statistical threshold for impairment and the criteria used to determine impairment for each cognitive domain. Prevalence of four MCI cognitive subtypes was determined according to nine different criteria and two types of normative data. Rates of CI were compared in persons of English-speaking and non-English-speaking backgrounds (NESB). RESULTS: Prevalence of CI ranged from 4 to 70% depending on the impairment criteria used. Agreement between different criteria was poor to moderate. This lack of consistency had greatest impact on MCI subtype classifications with many being reclassified as "normal" or into a different subtype when stringency of the criteria was increased or decreased. Higher rates of impairment were found in persons of NESB across all cognitive domains. CONCLUSIONS: The prevalence of CI was strongly affected by the choice of neuropsychological assessment parameters. Guidelines for operationalizing CI are required.

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.

Diffusion tensor imaging of the posterior cingulate is a useful biomarker of mild cognitive impairment.

OBJECTIVES: Mild cognitive impairment (MCI) is recognized as a predementia state, but its definition is inconsistent and only 20%-30% develop dementia after 2 years. Biomarkers may help identify individuals at greatest risk of progressive decline. The authors examine a novel neuroimaging technique, diffusion tensor imaging (DTI) as a potential biomarker of MCI. DESIGN: Cross-sectional prospective study. SETTING: Subjects were recruited randomly using the electoral roll from two electorates in East Sydney, Australia. PARTICIPANTS: A community-dwelling sample (N = 249) and age 70-90 years. MEASUREMENTS: Screening to exclude dementia, comprehensive neuropsychiatric assessment, cognitive test battery, structural magnetic resonance imaging and DTI to obtain measures of fractional anisotropy (FA) and mean diffusivity (MD). MCI was diagnosed by standard criteria. RESULTS: After controlling for age, sex, and years of education, the amnestic MCI (aMCI) group demonstrated microstructural pathology in the parahippocampal white matter, frontal white matter, splenium of corpus callosum, and posterior cingulate region. The nonamnestic MCI (naMCI) group demonstrated microstructural pathology in the frontal white matter, internal capsule, occipital white matter, and the posterior cingulate region. A binary logistic regression model showed that DTI of the left posterior cingulate was significant in identifying persons with aMCI to an accuracy of 85.1%. Receiver operating characteristics curve analysis yielded a sensitivity of 80% and specificity of 60.3% in distinguishing aMCI from naMCI and the normal comparison group. CONCLUSION: DTI of the posterior cingulate region discriminates MCI from cognitively normal individuals with accuracy and has the potential to be used as a biomarker of MCI, in particular aMCI.