Reading the Mind in the Eyes: A Population-Based Study of Social Cognition in Older Adults.

BACKGROUND: Social cognition indicates the cognitive processes involved in perceiving, interpreting, and processing social information. Although it is one of the six core DSM-5 cognitive domains for diagnosing neurocognitive disorders, it is not routinely assessed in older adults. The Reading the Mind in the Eyes Test assesses Theory of Mind, the social cognition mechanism which forms the root of empathy. OBJECTIVES: To describe the distribution of, and factors associated with, scores on a 10-item version of Reading the Mind in the Eyes Test (RMET-10) in older adults. DESIGN: Population-based cross-sectional study. SETTING: Small-town communities in Pennsylvania. PARTICIPANTS: Adults aged 66-105 years (N = 902, mean age = 76.6). MEASUREMENTS: The assessment included RMET-10, demographics, cognitive screening, literacy, depression symptoms, anxiety symptoms, cognitive composites derived from a neuropsychological test battery, Social Norms Questionnaire, and Clinical Dementia Rating (CDR). RESULTS: RMET-10 score was normally distributed in our overall study sample. Normative RMET-10 scores among those rated as CDR = 0 were calculated by age, sex, and education. RMET-10 score was significantly higher with younger age, higher education, white race, higher cognitive screening scores, literacy, social norms scores, higher scores in all five domains in cognitive composites, and lower CDR. RMET-10 score was also significantly higher with fewer depression and anxiety symptoms after adjusting for demographics. CONCLUSIONS: The RMET is a potentially useful measure of social cognition for use in the research assessment of older adults. With appropriate calibration it should also have utility in the clinical setting.

Relationships Between Executive Control Circuit Activity, Amyloid Burden, and Education in Cognitively Healthy Older Adults.

INTRODUCTION: In cognitively healthy older adults, amyloid-beta (Aß) burden is associated with greater activity on task-based functional magnetic resonance imaging. Higher levels of functional activation are associated with other factors along with amyloid and the authors investigated these relationships as well as how they relate to Aß in cognitively healthy older adults. METHODS: The authors recruited cognitive healthy older adults (N = 50) from the Pittsburgh community that underwent extensive cognitive batteries, activation during a working memory (digit symbol substitution task, DSST), positron emission tomography scan for Pittsburgh Compound B (PiB, measuring amyloid), and other demographic measures. The authors tested the association between DSST activation and global PiB, neurocognitive batteries, and education. RESULTS: The authors found that the DSST robustly activated expected structures involved in working memory. The authors found that greater global Aß deposition was associated with greater DSST activation in the right calcarine, precuneus, middle temporal as well as the left insula and inferior frontal gyrus. The authors also found that greater education was associated with lower DSST activation - however this was not significant after adjusting for Aß. DISCUSSION: Greater amyloid was associated with greater activation, which may represent compensatory activation. Greater education was associated with lower activation, which may represent more efficient activation (i.e., less activation for the same task). After adjusting for amyloid, education was not significantly associated with activation suggesting that during the preclinical stage amyloid is the primary determinant of activation. Further, activation was not associated with cognitive function. Compensatory activation in the preclinical stage may help maintain cognitive function.

The Relationship of Current Cognitive Activity to Brain Amyloid Burden and Glucose Metabolism.

Several studies have investigated how lifetime cognitive engagement affects levels of amyloid-beta (Aß) deposition in the brain. However, there has been some disagreement, leaving the relationship of cognitive activity (CA) to Aß a largely open question. The present study investigated the relationship between CA, Aß deposition, and glucose metabolism. One hundred nine cognitively normal participants underwent Pittsburgh Compound-B (PiB) and [18F]fluorodeoxyglucose-positron emission tomography and completed a questionnaire designed to measure current CA. Statistical analyses revealed significant differences in PiB retention between those in the high and low CA groups. Linear regression models revealed a significant negative relationship between PiB retention and CA and a significant positive relationship between glucose metabolism and CA. These data suggest that CA may have a direct beneficial effect on the pathophysiology of AD or reflect another underlying process that results in both higher CA and lower AD pathophysiology.

Amyloid-Beta Deposition is Associated with Increased Medial Temporal Lobe Activation during Memory Encoding in the Cognitively Normal Elderly.

BACKGROUND: Much is unknown about changes that occur in the brain in the years preceding the cognitive and functional impairment associated with Alzheimer disease (AD). This period before mild cognitive impairment is present has been referred to as preclinical AD, and is thought to begin with amyloid-beta deposition and then progress to neurodegeneration and functional brain circuit alterations. Prior studies have shown that there is increased medial temporal lobe activation on functional magnetic resonance imaging (fMRI) early in the course of mild cognitive impairment. It is unknown, however, whether this altered fMRI activity precedes cognitive impairment. The purpose of this study is to address this question using Pittsburgh Compound-B (PiB) imaging and fMRI in a sample of cognitively normal older adults. METHODS: Forty-four cognitively normal older adults underwent both PiB imaging and fMRI with a face-name memory task: 21 were classified as PiB(+) and 23 were PiB(-). Additionally, thorough cognitive and neuropsychological test batteries were administered outside the scanner. The main outcome measure in this study is fMRI activation in the medial temporal lobe during a face-name memory-encoding task. RESULTS: PiB(+) subjects showed higher fMRI activation during the memory task in the hippocampus relative to PiB(-) participants. CONCLUSIONS: The increased medial temporal lobe activation in preclinical AD, observed in this study, may serve as an early biomarker of neurodegeneration. Future studies are needed to clarify whether this functional biomarker can stratify AD risk among PiB(+) older adults.

Rates and risk factors for progression to incident dementia vary by age in a population cohort.

OBJECTIVE: To estimate rate of progression from normal cognition or mild impairment to dementia, and to identify potential risk and protective factors for incident dementia, based on age at dementia onset in a prospective study of a population-based cohort (n = 1,982) aged 65 years and older. METHODS: Following the cohort annually for up to 5 years, we estimated incidence of dementia (Clinical Dementia Rating ≥1) among individuals previously normal or mildly impaired (Clinical Dementia Rating 0 or 0.5). In the whole cohort, and also stratified by median onset age, we examined several vascular, metabolic, and inflammatory variables as potential risk factors for developing dementia, using interval-censored survival models. RESULTS: Based on 67 incident cases of dementia, incidence rate (per 1,000 person-years) was 10.0 overall, 5.8 in those with median onset age of 87 years or younger, and 31.5 in those with onset age after 87 years. Adjusting for demographics, the risk of incident dementia with onset age of 87 years or younger (n = 33) was significantly increased by baseline smoking, stroke, low systolic blood pressure, and APOE*4 genotype, and reduced by current alcohol use. Among those with dementia with onset after 87 years (n = 34), no risk or protective factor was significant. CONCLUSION: Risk and protective factors were only found for incident dementia with onset before the median onset age of 87 years, and not for those with later onset. Either unexplored risk factors explain the continued increase in incidence with age, or unknown protective factors are allowing some individuals to delay onset into very old age.

How well do MCI criteria predict progression to severe cognitive impairment and dementia?

BACKGROUND: The International Working Group (IWG) criteria for mild cognitive impairment have variable utility in predicting progression to dementia, partly depending on the setting. We explored an empiric approach to optimize the criteria and cutoff points in a population study. METHODS: In a cohort of adults aged 65 years or older, we identified 1129 individuals with normal or only mildly impaired cognition by cognitive classification, and 1146 individuals without dementia (Clinical Dementia Rating <1). Operationally defining the IWG criterion set, we examined its sensitivity and specificity for the development of severe cognitive impairment and dementia (Clinical Dementia Rating ≥1) over 4 years. We then disaggregated the criteria and used Classification and Regression Tree analyses to identify the optimal predictive model. RESULTS: The operational IWG criteria had 49% sensitivity and 86% specificity for the outcome of severe cognitive impairment, and 40% sensitivity and 84% specificity for the outcome of dementia. Classification and Regression Tree modeling improved sensitivity to 82% for the cognitive outcome and 76% for the dementia outcome; specificity remained high. Memory scores were the most important predictors for both outcomes. The optimal cutoff points were around 1.0 SD below the age-education mean. The best fit was observed when prediction was modeled separately for each age-education group. CONCLUSIONS: Objective cognitive measurements contributed more to the prediction of dementia than subjective and functional measures. Those with less education only required memory testing, whereas those with more education required assessment of several cognitive domains. In cases in which only overall norms are available, the appropriate threshold will vary according to the individual's age and education.