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Background: Conceptualizing cognitive aging as a step-sequential process is useful in identifying particular stages of cognitive function and impairment., Objective: We applied latent transition analysis (LTA) to determine 1) whether the underlying structure of cognitive profiles found at every measurement occasion are uniform across three waves of assessment, 2) whether class-instability is predictive of distal outcomes, and 3) whether class-reversions from impaired to non-impaired using latent modelling is lower than when using clinical criteria of mild cognitive impairment (MCI)., Methods: A mover-stayer LTA model with dementia as a distal outcome was specified to model transitions of ten neuropsychological measures over three annual waves in the Rush Memory and Aging Project (n = 1,661). The predictive validity of the mover-stayer status for incident Alzheimer's disease (AD) was then assessed., Results: We identified a five-class model across the three time-points: Mixed-Domain Impairment, Memory-Specific Impairment, Frontal Impairment, Average, and Superior Cognition. None of the individuals in the Impairment classes reverted to the Average or Superior classes. Conventional MCI classification identified 26.4% and 14.1% at Times 1 and 2 as false-positive cases. "Movers" had 87% increased risk of developing dementia compared to those classified as "Stayers"., Conclusion: Our findings support the use of latent variable modelling that incorporates comprehensive neuropsychological assessment to identify and classify cognitive impairment.

Background: The Memory Binding Test (MBT) demonstrated good cross-sectional discriminative validity and predicted incident aMCI., Objective: To assess whether the MBT predicts incident dementia better than a conventional list learning test in a longitudinal community-based study., Methods: As a sub-study in the Einstein Aging Study, 309 participants age≥70 initially free of dementia were administered the MBT and followed annually for incident dementia for up to 13 years. Based on previous work, poor memory binding was defined using an optimal empirical cut-score of≤17 on the binding measure of the MBT, Total Items in the Paired condition (TIP). Cox proportional hazards models were used to assess predictive validity adjusting for covariates. We compared the predictive validity of MBT TIP to that of the free and cued selective reminding test free recall score (FCSRT-FR; cut-score:≤24) and the single list recall measure of the MBT, Cued Recalled from List 1 (CR-L1; cut-score:≤12)., Results: Thirty-five of 309 participants developed incident dementia. When assessing each test alone, the hazard ratio (HR) for dementia was significant for MBT TIP (HR = 8.58, 95% CI: (3.58, 20.58), p < 0.0001), FCSRT-FR (HR = 4.19, 95% CI: (1.94, 9.04), p = 0.0003) and MBT CR-L1 (HR = 2.91, 95% CI: (1.37, 6.18), p = 0.006). MBT TIP remained a significant predictor of dementia (p = 0.0002) when adjusting for FCSRT-FR or CR-L1., Conclusions: Older adults with poor memory binding as measured by the MBT TIP were at increased risk for incident dementia. This measure outperforms conventional episodic memory measures of free and cued recall, supporting the memory binding hypothesis.

The objective of this study was to investigate the relationship of medial temporal lobe and posterior cingulate cortex (PCC) volumetrics as well as fractional anisotropy of the cingulum angular bundle (CAB) and the cingulum cingulate gyrus (CCG) bundle to performance on measures of verbal memory in non-demented older adults. The participants were 100 non-demented adults over the age of 70 years from the Einstein Aging Study. Volumetric data were estimated from T1-weighted images. The entire cingulum was reconstructed using diffusion tensor MRI and probabilistic tractography. Association between verbal episodic memory and MRI measures including volume of hippocampus (HIP), entorhinal cortex (ERC), PCC and fractional anisotropy of CAB and CCG bundle were modeled using linear regression. Relationships between atrophy of these structures and regional cingulum fractional anisotropy were also explored. Decreased HIP volume on the left and decreased fractional anisotropy of left CAB were associated with lower memory performance. Volume changes in ERC, PCC and CCG disruption were not associated with memory performance. In regression models, left HIP volume and left CAB-FA were each independently associated with episodic memory. The results suggest that microstructural changes in the left CAB and decreased left HIP volume independently influence episodic memory performance in older adults without dementia. The importance of these findings in age and illness-related memory decline require additional exploration., Competing Interests: All authors declare that there are no financial, personal, or other potential conflicts of interest to report.

Background: The Memory Binding Test (MBT), previously known as Memory Capacity Test, has demonstrated discriminative validity for distinguishing persons with amnestic mild cognitive impairment (aMCI) and dementia from cognitively normal elderly., Objective: We aimed to assess the predictive validity of the MBT for incident aMCI., Methods: In a longitudinal, community-based study of adults aged 70+, we administered the MBT to 246 cognitively normal elderly adults at baseline and followed them annually. Based on previous work, a subtle reduction in memory binding at baseline was defined by a Total Items in the Paired (TIP) condition score of ≤22 on the MBT. Cox proportional hazards models were used to assess the predictive validity of the MBT for incident aMCI accounting for the effects of covariates. The hazard ratio of incident aMCI was also assessed for different prediction time windows ranging from 4 to 7 years of follow-up, separately., Results: Among 246 controls who were cognitively normal at baseline, 48 developed incident aMCI during follow-up. A baseline MBT reduction was associated with an increased risk for developing incident aMCI (hazard ratio (HR) = 2.44, 95% confidence interval: 1.30-4.56, p = 0.005). When varying the prediction window from 4-7 years, the MBT reduction remained significant for predicting incident aMCI (HR range: 2.33-3.12, p: 0.0007-0.04)., Conclusion: Persons with poor performance on the MBT are at significantly greater risk for developing incident aMCI. High hazard ratios up to seven years of follow-up suggest that the MBT is sensitive to early disease.

This study examined the relationship between endogenous hormones and cognitive function in nondemented, ethnically-diverse community-dwelling older men enrolled in the Einstein Aging Study (EAS). All eligible participants (185 men, mean age=81 years) received neuropsychological assessment (Free and Cued Selective Reminding Test (FCSRT), Logical Memory (LM), Trail Making Test B (TMTB), block design (BD)) and provided blood samples for hormonal assays (total estradiol, total testosterone, calculated free testosterone index). Linear regression analysis adjusted for age, education, body mass index, and cardiovascular comorbidities indicated that men with high levels of total estradiol demonstrated better FCSRT verbal memory performance (β=0.17, p<0.02) compared to men with lower levels of total estradiol. The results remained unchanged when the model was further adjusted for ethnicity. We did not detect an association between testosterone and cognitive performance. These findings indicate that high levels of total estradiol in older men are associated with better performance on a cue-based, controlled learning test of verbal memory that is a sensitive predictor of dementia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Episodic memory loss, a hallmark symptom of Alzheimer's Disease, is frequently quantified by story memory performance. The National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDSNB) replaced Logical Memory with Craft Story 21 in UDSNB Version 3. The concordance between these story memory tasks is poorly characterized in demographically diverse older adults, possibly jeopardizing the integrity of longitudinal data in aging cohorts. Method: Einstein Aging Study participants (n = 298; Mage = 76.6; Meducation = 15; 66.4% women; 43.3% Non-Hispanic White) completed UDSNB measures, including Craft Story and Logical Memory. Classification as normal cognition (n = 206) or mild cognitive impairment (n = 90) was based on Jak/Bondi criteria. Analyses included correlations, linear regression, and equipercentile equating methods to characterize the relationship between Logical Memory and Craft Story. Multivariate linear mixed effects models explored the association of covariates and practice effects over follow-up, stratified by cognitive status and race/ethnicity. Results: Immediate (r = 0.54) and delayed (r = 0.56) versions of Logical Memory and Craft Story were moderately correlated. Age, education, depression, and female sex were associated with Logical Memory, while age, education, cognitive status, and male sex were associated with Craft Story. Significant differential effects of sex on story memory were observed. Conclusions: We demonstrated that Logical Memory and Craft Story may be used largely interchangeably; however, memory may be enhanced for stories with a protagonist of the same sex as the participant. Craft Story was somewhat more associated with mild cognitive impairment in the overall sample, but especially in non-Hispanic Black participants. We discuss how results inform test selection considerations. [ABSTRACT FROM AUTHOR]

Monitoring early changes in cognitive performance is useful for studying cognitive aging as well as for detecting early markers of neurodegenerative diseases. Repeated evaluation of cognition via a measurement burst design can accomplish this goal. In such design participants complete brief evaluations of cognition, multiple times per day for several days, and ideally, repeat the process once or twice a year. However, long-term cognitive change in such repeated assessments can be masked by short-term within-person variability and retest learning (practice) effects. In this paper, we show how a Bayesian double exponential model can account for retest gains across measurement bursts, as well as warm-up effects within a burst, while quantifying change across bursts in peak performance. We also highlight how this approach allows for the inclusion of person-level predictors and draw intuitive inferences on cognitive change with Bayesian posterior probabilities. We use older adults' performance on cognitive tasks of processing speed and spatial working memory to demonstrate how individual differences in peak performance and change can be related to predictors of aging such as biological age and mild cognitive impairment status. [ABSTRACT FROM AUTHOR]

Objectives: The current study examined whether self-reported memory problems among cognitively intact older adults changed concurrently with, preceded, or followed depressive symptoms over time.Design: Data were collected annually via in-person comprehensive medical and neuropsychological examinations as part of the Einstein Aging Study.Setting: Community-dwelling older adults in an urban, multi-ethnic area of New York City were interviewed.Participants: The current study included a total of 1,162 older adults (Mage = 77.65, SD = 5.03, 63.39% female; 74.12% White). Data were utilized from up to 11 annual waves per participant.Measurements: Multilevel modeling tested concurrent and lagged associations between three types of memory self-report (frequency of memory problems, perceived one-year decline, and perceived ten-year decline) and depressive symptoms.Results: Results showed that self-reported frequency of memory problems covaried with depressive symptoms only in participants who were older at baseline. Changes in perceived one-year and ten-year memory decline were related to changes in depressive symptoms across all ages. Depressive symptoms increased the likelihood of perceived ten-year memory decline the next year; however, perceived ten-year memory decline did not predict future depressive symptoms. Additionally, no significant temporal relationship was observed between depressive symptoms and self-reported frequency of memory problems or perceived one-year memory decline.Conclusion: Our findings highlight the importance of testing the unique associations of different types of self-reported memory problems with depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that higher quality of life would be associated with better cognitive function and a reduced risk of incident all cause dementia and Alzheimer disease (AD) in older adults.Materials and Methods: Participants included 1183 older adults with an average age of 78.2 (SD=5.3) from Einstein Aging Study. The 36-Item Short-Form Health Survey was used to measure health-related quality of life (HRQoL). We investigated baseline associations between the cognitive domains of memory, executive function, and general fluid ability with 8 subscales of the 36-Item Short-Form Health Survey (physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, social functioning, role limitations due to emotional problems, vitality, and general mental health) and the 2 component summary scores of physical component summary (PCS) and mental component summary (MCS). Next, we used Cox proportional hazard models to assess the predictive validity of HRQoL subscales for the onset of incident dementia and incident AD.Results: At baseline, higher scores (better HRQoL) on MCS and its 4 subscales (social functioning, role limitations due to emotional problems, vitality, and general mental health) were associated with higher performance on both memory and executive function domains. Higher scores in role limitation due to physical problems, role limitation due to emotional problems, and general mental health subscales were associated with reduced risk of incident dementia. Higher MCS, but not PCS, predicted a reduced incident of all-cause dementia and AD.Conclusions: These findings suggest that diminution of HRQoL precedes the onset of diagnosable dementia and may be useful in the prediction of dementia onset. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer's disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests.Participants: 4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates.Results: All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66 - 9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC.Conclusions: Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI. [ABSTRACT FROM AUTHOR]

Background: In this study we investigated the role of hippocampal volume (HV) in visual memory. Methods: Participants were a subsample of older adults (> = 70 years) from the Einstein Aging Study. Visual performance was measured using the Complex Figure (CF) copy and delayed recall tasks from the Repeatable Battery for the Assessment of Neuropsychological Status. Linear regressions were fitted to study associations between HV and visual tasks. Results: Participants’ (n = 113, mean age = 78.9 years) average scores on the CF copy and delayed recall were 17.4 and 11.6, respectively. CF delayed recall was associated with total (β = .031, p = 0.001) and left (β = 0.031, p = 0.001) and right HVs (β = 0.24, p = 0.012). CF delayed recall remained significantly associated with left HV even after we also included right HV (β = 0.27, p = 0.025) and the CF copy task (β = 0.30, p = 0.009) in the model. CF copy did not show any significant associations with HV. Conclusion: Our results suggest that left HV contributes in retrieval of visual memory in older adults. [ABSTRACT FROM AUTHOR]

Background: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline.Methods and Findings: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China.Conclusions: Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data. [ABSTRACT FROM AUTHOR]

Objective: To contrast four approaches to norming two widely used memory tests in older adults for the purpose of detecting preclinical dementia. Method: The study sample included participants from the Einstein Aging Study who were over age 70, were free of dementia at baseline, and were followed for at least 5 years. Norms were derived from a conventional sample (excluding individuals with dementia at baseline but not those who developed dementia during follow-up) and a robust normative sample (excluding persons with dementia at baseline as well as those who developed dementia over 5 years of follow-up). Both normative samples were examined with and without adjustment for age and education. We contrasted the picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR) and the Logical Memory (LM) test for their ability to identify persons with preclinical dementia, operationally defined by the development of diagnosable dementia over 5 years of follow-up, using these four approaches to developing norms for detecting preclinical dementia. Results. Of 418 participants included in the conventional normative sample, the mean age was 78.2 years, and 59% were female. There were 78 incident cases of dementia over 5 years leaving 340 participants in the robust normative sample. Means and standard deviations were defined for both the conventional and robust normative samples, and cut-scores with and without adjustment were set at 1.5 standard deviations below the mean of each test. As predicted, in comparison with the conventional sample, the robust sample had higher cut-scores, which provided higher sensitivity for detecting preclinical dementia. This effect persisted regardless of adjustment. The pFCSRT+IR was more sensitive than LM in detecting incident dementia cases. Conclusion: When using cognitive test norms to identify preclinical dementia, robust norming procedures improves detection using both the pFCSRT+IR and LM. [ABSTRACT FROM AUTHOR]

Longitudinal administration of neuropsychological instruments are often used to assess age-related changes in cognition. Informative loss to follow-up may bias the results of these studies. Herein, we use auxiliary data to adjust for informative loss to follow-up. In the Einstein Aging Study, memory was assessed annually in a community sample of adults age 70 +, free of dementia at baseline, using the free recall from the Free and Cued Selective Reminding Test, and via telephone using the Memory Impairment Screen for Telephone (the auxiliary data). Joint linear mixed models were used to assess how the effect of the APOE e4 genotype may be affected by informative missingness in the in-person data. A total of 620 EAS participants contributed 2085 person years of follow-up to the analyses. Memory decline rates estimated in joint models were 19% greater in ε4 negative participants and 27% greater in e4 positive participants compared to traditional approaches; the effect of APOE e4 on memory decline was 37% greater. Joint modeling methods can help address bias caused by informative missing data in the estimation of the effect of risk factors on cognitive change, and may be applicable to a broader range of outcomes in longitudinal aging studies. [ABSTRACT FROM AUTHOR]

Mixed findings have been reported on the relationship between hippocampal integrity and major depression in clinical populations. Few neuroimaging studies have investigated associations between hippocampal measures and depressive symptoms in nondemented older adults. Here, we address this issue by imaging 36 nondemented adults over age 70 from the Einstein Aging Study, a community-based sample from the Bronx, NY. Depressive symptoms were assessed using the 15-item Geriatric Depression scale (GDS). Clinically significant depression was defined using a cut-off score of 5 or greater. Hippocampal data included MRI-derived volume data normalized to midsagittal area and MRS-derived N-acetylaspartate to creatine ratios (NAA/Cr). Our result indicates that smaller total hippocampal volume was associated with higher GDS scores, but there were no significant association between hippocampal NAA/Cr and GDS score. These effects were consistent after controlling for age, education, and gender. Reduction in hippocampal volume could represent a risk factor or a consequence of depression in older adults. Further studies are needed to better understand the role of the hippocampus in the development and experience of depression in older adults. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives: To develop and assess telephone-based screening tests for dementia, especially Alzheimer's disease (AD). Design: A cross-sectional validation study nested within a longitudinal study of aging and dementia. Setting: The Einstein Aging Study of the Albert Einstein College of Medicine, Bronx, New York. Participants: Three hundred elderly community volunteers living in Bronx County, 27 of whom were diagnosed with dementia based on in-person clinical evaluation. Of the 27 individuals with dementia, 18 had AD. Measurements: A telephone battery was administered that included the Memory Impairment Screen by telephone (MIS-T, a test of semantic memory), the Category Fluency Test (CF-T), and the Telephone Instrument for Cognitive Status (TICS). An in-person evaluation then followed that included a neurological examination, a neuropsychological battery, demographics, and medical history. Results: The telephone battery was well accepted. The MIS-T required 4 minutes; the CF-T, 3 minutes; and the TICS, 10 minutes. The MIS-T had excellent sensitivity and specificity when compared with the CF-T and the TICS. Using cutscores on all three tests that provide a sensitivity of 78%, specificity was significantly higher for the MIS-T (93%) than for the CF-T (78%, P <.05) or the TICS (80%, P <.05). Combining the MIS-T and CF-T improved discriminative validity but increased screening time and the complexity of scoring. Normative data for the MIS-T, the CF-T, and the TICS for use in settings with different base rates (prevalence) of dementia are presented in this study. Conclusion: The MIS-T outperforms the CF-T and the TICS as a valid and time-efficient telephone screen for dementia. For applications that require optimal efficiency and accuracy, the MIS-T is recommended. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To improve screening for Alzheimer's disease (AD) with the Memory Impairment Screen (MIS), a 4-minute, four-item delayed free and cued recall memory test with controlled learning and high discriminative validity. To assess the discriminative validity of the MIS for AD and to compare it with the conventional three-word memory test, a delayed free recall task, widely recommended as a dementia-screening test in clinical practice. DESIGN: Cross-sectional validation study nested within a longitudinal study of aging and dementia. The MIS and the standard three-word memory task were administered as part of a comprehensive neurological and neuropsychological evaluation. SETTING: Einstein Aging Study at the Albert Einstein College of Medicine, Bronx, New York. PARTICIPANTS: Two hundred forty community-dwelling older adults. MEASUREMENTS: Sensitivity, specificity, and positive predictive value (PPV) were calculated for the MIS and three-word memory test as screening tests for AD. RESULTS: In comparison with the three-word memory task, the MIS had higher sensitivity (.86 vs .65), higher specificity (.97 vs .85), and greater PPV (.80 vs .37) as a screen for AD. CONCLUSIONS: The MIS had high discriminative validity as a screening test for AD and substantially outperformed the three-word memory task. Given its validity and brevity, the MIS has important advantages as an AD screen for use in primary care. [ABSTRACT FROM AUTHOR]