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.

Effects of Statins on Memory, Cognition, and Brain Volume in the Elderly.

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 Eε4 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 Eε4 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.

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.

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.

Age-associated differences on structural brain MRI in nondemented individuals from 71 to 103 years.

Successful brain aging in the oldest old (≥90 years) is underexplored. This study examined cross-sectional brain morphological differences from 8th to 11th decades of life in nondemented individuals by high-resolution magnetic resonance imaging. Two hundred seventy-seven nondemented community-dwelling participants (71-103 years) from Sydney Memory and Ageing Study and Sydney Centenarian Study comprised the sample, including a subsample of 160 cognitively high-functioning elders. Relationships between age and magnetic resonance imaging-derived measurements were studied using general linear models; and structural profiles of the ≥90 years were delineated. In full sample and the subsample, significant linear negative relationship of gray matter with age was found, with the greatest age effects in the medial temporal lobe and parietal and occipital cortices. This pattern was further confirmed by comparing directly the ≥90 years to the 71-89 years groups. Significant quadratic age effects on total white matter and white matter hyperintensities were observed. Our study demonstrated heterogeneous differences across brain regions between the oldest old and young old, with an emphasis on hippocampus, temporoposterior cortex, and white matter hyperintensities.

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.

Structural MRI Biomarkers of Mild Cognitive Impairment from Young Elders to Centenarians.

UNLABELLED: Underpinnings of mild cognitive impairment (MCI) change with increasing age. We hypothesize that MRI signatures of mild cognitive impairment (MCI) would be different at a higher age compared to younger elders. METHODS: 244 participants (71-103 years) from the Sydney Memory and Ageing Study and the Sydney Centenarian Study were categorized as amnestic MCI (aMCI), non-amnestic MCI (naMCI) or cognitively normal (CN). Brain "atrophy" and white matter hyper-intensities (WMHs) associated with MCI subtypes and age effects were examined by general linear models, controlling for confounding factors. Reduced logistic regressions were performed to determine structures that best discriminated aMCI from CN in individuals <85 and those ≥85 years. RESULTS: aMCI was associated with smaller volumes of overall cortex, medial temporal structures, anterior corpus callosum, and select frontal and parietal regions compared to CN; such associations did not significantly change with age. Structures that best discriminated aMCI from CN differed however in the <85 and ≥85 age groups: cortex, putamen, parahippocampal, precuneus and superior frontal cortices in <85 years, and the hippocampus, pars triangularis and temporal pole in ≥85 years. Differences between naMCI and CN were small and non-significant in the sample. WMHs were not significantly associated with MCI subtypes. CONCLUSIONS: Structural MRI distinguishes aMCI, but not naMCI, from CN in elderly individuals. The structures that best distinguish aMCI from CN differ in those <85 from those ≥85, suggesting different neuropathological underpinnings of cognitive impairment in the very old.

The Relationship Between Plasma Aß Levels, Cognitive Function and Brain Volumetrics: Sydney Memory and Ageing Study.

OBJECTIVES: Determine whether (1) a relationship exists between plasma amyloid-ß (Aß)1- 40 and 1-42 peptide levels, brain volumetrics and cognitive performance in elderly individuals with and without amnestic mild cognitive impairment (aMCI), (2) plasma Aß peptide levels differ between apolipoprotein E (APOE) ε4 carriers and non-carriers and (3) longitudinal changes in cognition and brain volume relate to Aß levels. METHODS: Subjects with aMCI (n = 89) and normal cognition (n = 126) were drawn from the Sydney Memory and Aging Study (Sydney MAS), a population based study of non-demented 70-90 year old individuals; 39 Alzheimer's disease (AD) patients were recruited from a specialty clinic. Sydney MAS participants underwent brain MRI scans and were assessed on 19 cognitive measures and were APOE ε4 genotyped. Plasma levels of Aß1-40 and 1-42 were quantified using ELISA. RESULTS: Wave1 plasma levels of Aß peptides and Aß1-42/1-40 ratio were lower in aMCI and AD, and Aß1-42 was positively associated with global cognition and hippocampal volume and negatively with white matter hyperintensities. The relationships of Aß1-40 and Aß1-42 were predominantly observed in ε4 allele carriers and non-carriers respectively. Longitudinal analysis revealed greater decline in global cognition and memory for the highest quintiles of Aß1-42 and the ratio measure. CONCLUSION: Plasma Aß levels and the Aß1-42/1-40 ratio are related to cognition and hippocampal volumes, with differential associations of Aß1-40 and Aß1-42 in ε4 carriers and non-carriers. These data support the Aß sink model of AD pathology, and suggest that plasma Aß measures may serve as biomarkers of AD.

Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies.

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes.

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.

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.

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.

The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.

Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p < 0.005). Stable IFG did not show greater decline in global cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are associated with accelerated decline in global cognition and brain volumes in non-demented elderly, whereas stable IFG is not. Preventing deterioration in glucose metabolism in the elderly may help preserve brain structure and function.

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.

Dementia in the oldest old.

People over the age of 90 years--the oldest old--are the fastest growing sector of the population. A substantial proportion of these individuals are affected by dementia, with major implications for the individual as well as society. Research on dementia in the oldest old is important for service planning, and the absence of dementia at this exceptional old age may serve as a model of successful ageing. This Review summarizes population-based epidemiological studies of dementia and its underlying neuropathology in nonagenarians and centenarians. The available data, although somewhat limited, show an age-specific and sex-specific profile of dementia status in very late life, resulting from a variety of neuropathologies that often co-occur. Extensive overlap in neuropathology between cognitively normal and cognitively impaired individuals is evident despite challenges to gathering data particular to this population. A complex picture is emerging of multiple pathogenetic mechanisms underlying dementia, and of the potential risk and protective factors for dementia that interact with genetics and lifestyle in normal and exceptional cognitive ageing.

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.

Challenges of diagnosing dementia in the oldest old population.

People aged 90 and older are the fastest growing age group in most parts of the world. Since the prevalence of dementia has been shown to increase exponentially after the age of 65, there is an acceptance that the oldest old population has a high burden of dementia; however, there is a lack of consensus on how best to diagnose dementia in this population. This review summarizes the various approaches to diagnosing dementia and the prevalence and incidence rates of dementia that have been reported. We also summarize the literature on cognitive and functional performance and biomarkers for dementia and discuss the limitations to interpretation of these data. Finally, we make recommendations for both researchers and clinicians who intend to diagnose dementia in the oldest old population.

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.