Andrea R. Zammit

Association Between Renal Function and Cognitive Ability Domains in the Einstein Aging Study: A Cross-Sectional Analysis

BACKGROUND The relationships between renal function and specific domains of cognitive function have rarely been explored in representative, community-based samples of older adults. We assessed the association between renal and cognitive function based on an extensive battery of neurocognitive tests. METHODS In a sample of Einstein Aging Study participants (n = 649, age = 70+ years) we calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration formula. We predefined three groups based on eGFR units of mL/min/1.73 m(2) as low (<45), medium (45-59), and high (≥60). Thirteen neurocognitive tests were subjected to principle component analysis revealing three components: a global component, an episodic memory component, and a frontal-executive component. We first examined the relationship of eGFR group to cognitive performance in each domain and then examined subtests for the domains which proved to be statistically significant. RESULTS The sample (mean = 79.2, 61% = female) was distributed among eGFR categories as follows: low (n = 67), medium (n = 151), and high (n = 431). The frontal-executive domain was significantly associated with poor cognitive performance in the low eGFR group (p <.001). When we examined the neuropsychological test components for frontal-executive domain, performance was lower on two of four contributing tests (Trail Making Test Part B and the Digit Symbol Substitution test). Other domains of cognitive function were not associated with eGFR. CONCLUSIONS Low eGFR is associated with reduced performance on executive function. Individuals with poor renal function should be assessed for cognitive impairment. Potential mechanisms are discussed.

Differential association of left and right hippocampal volumes with verbal episodic and spatial memory in older adults.

The hippocampus plays a critical role in verbal and spatial memory, thus any pathological damage to this formation may lead to cognitive impairment. It is suggested that right and left hippocampi are affected differentially in healthy or pathologic aging. The purpose of this study was to test the hypothesis that verbal episodic memory performance is associated with left hippocampal volume (HV) while spatial memory is associated with right HV. 115 non-demented adults over age 70 were drawn from the Einstein Aging Study. Verbal memory was measured using the free recall score from the Free and Cued Selective Reminding Test - immediate recall (FCSRT-IR), logical memory immediate and delayed subtests (LM-I and LM-II) from the Wechsler Memory Scale-Revised (WMS-R). Spatial Memory was measured using a computerized dot memory paradigm that has been validated for use in older adults. All participants underwent 3T MRI with subsequent automatized measurement of the volume of each hippocampus. The sample had a mean age of 78.7 years (SD=5.0); 57% were women, and 52% were white. Participants had a mean of 14.3 years (SD=3.5) of education. In regression models, two tests of verbal memory (FCSRT-IR free recall and LM-II) were positively associated with left HV, but not with right HV. Performance on the spatial memory task was associated with right HV, but not left HV. Our findings support the hypothesis that the left hippocampus plays a critical role in episodic verbal memory, while right hippocampus might be more important for spatial memory processing among non-demented older adults.

Profiles of physical, emotional and psychosocial wellbeing in the Lothian birth cohort 1936

BackgroundPhysical, emotional, and psychosocial wellbeing are important domains of function. The aims of this study were to explore the existence of separable groups among 70-year olds with scores representing physical function, perceived quality of life, and emotional wellbeing, and to characterise any resulting groups using demographic, personality, cognition, health and lifestyle variables.MethodsWe used latent class analysis (LCA) to identify possible groups.ResultsResults suggested there were 5 groups. These included High (n = 515, 47.2% of the sample), Average (n = 417, 38.3%), and Poor Wellbeing (n = 37, 3.4%) groups. The two other groups had contrasting patterns of wellbeing: one group scored relatively well on physical function, but low on emotional wellbeing (Good Fitness/ Low Spirits,n = 60, 5.5%), whereas the other group showed low physical function but relatively well emotional wellbeing (Low Fitness/Good Spirits, n = 62, 5.7%). Salient characteristics that distinguished all the groups included smoking and drinking behaviours, personality, and illness.ConclusionsDespite there being some evidence of these groups, the results also support a largely one-dimensional construct of wellbeing in old age—for the domains assessed here—though with some evidence that some individuals have uneven profiles.

Roles of hippocampal subfields in verbal and visual episodic memory

HighlightsNeurocognitive tests tapping specific HC subfields can help target at‐risk individuals.Subiculum was associated with verbal and visual episodic memory.CA1 was associated with verbal and visual episodic memory.No other subfields were associated with verbal or visual episodic memory.Our results suggest that CA1 and subiculum are responsible for retrieval. Introduction: Selective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer’s disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults. Methods: This study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community‐based study of non‐demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2‐CA3, CA4‐dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume. Results: Participants had a mean age of 78.9 (SD = 5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (&bgr; = 0.31, p = 0.001) and FCSRT Delayed Recall (&bgr; = 0.27, p = 0.007); subiculum volume was associated with Complex Figure Delayed Recall (&bgr; = 0.27, p = 0.002) and FCSRT Delayed Recall (&bgr; = 0.24, p = 0.010); CA1 was associated with Complex Figure Delayed Recall (&bgr; = 0.26, p < 0.002) and FCSRT Delayed Recall (&bgr; = 0.20, p = 0.025). Conclusions: Our findings confirm previous research on the specific roles of CA1 and subiculum in episodic memory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory.

Chronic Kidney Disease in Non-Diabetic Older Adults: Associated Roles of the Metabolic Syndrome, Inflammation, and Insulin Resistance

Background The aims of the study were to examine the association between CKD and the metabolic syndrome (MetS) and its components in older adults. We also explored two possible pathways linking the metabolic syndrome with CKD: inflammation as measured by high sensitivity C-Reactive Protein (hsCRP) and insulin resistance as measured by HOMA-IR. Methods Community-dwelling non-diabetic 70+ adults from the Einstein Aging Study participated in the study. We defined CKD as eGFR below 60mL/min/1.73m2. MetS was defined according to recent guidelines from the National Cholesterol Education Program. Binary logistic regressions were used to assess the association between the metabolic syndrome, its components and CKD with adjustments for demographics, HOMA-IR and hsCRP. Results Of 616 participants (mean age = 79.3 years, 65.5% female), 25% had MetS and 26.5% had CKD. Participants with CKD had a significantly higher prevalence of the MetS than individuals without CKD (34.4% vs. 24.3%). Binary logistic regression models showed that CKD was associated with MetS (OR = 1.72, 95%CI = 1.13–2.61). The association was unaltered by adjustment for hsCRP but altered by adjustment for HOMA-IR. As the number of MetS components increased the relative odds of CKD also increased. None of the individual components was independently associated with CKD. Conclusion MetS is associated with CKD in non-diabetic older adults. Results showed that as the number of MetS components increased so did the odds for CKD. HOMA-IR seems to be in the casual pathway linking MetS to CKD.

Low eGFR is associated with dysexecutive and amnestic mild cognitive impairment

Few studies have explored the association between renal function and major subtypes of mild cognitive impairment (MCI).

Patterns and associates of cognitive function, psychosocial wellbeing and health in the Lothian Birth Cohort 1936

BackgroundCognitive function, psychosocial wellbeing and health are important domains of function. Consistencies and inconsistencies in patterns of wellbeing across these domains may be informative about wellbeing in old age and the ways it is manifested amongst individuals. In this study we investigated whether there were groups of individuals with different profiles of scores across these domains. We also aimed to identify characteristics of any evident groups by comparing them on variables that were not used in identifying the groups.MethodsThe sample was the Lothian Birth Cohort 1936, which included 1091 participants born in 1936. They are a community-dwelling, narrow-age-range sample of 70-year-olds. Most had taken part in the Scottish Mental Survey 1947 at an average age of 11, making available a measure of childhood intelligence. We used latent class analysis (LCA) to explore possible profiles using 9 variables indicating cognitive functioning, psychosocial wellbeing and health status. Demographic, personality, and lifestyle variables – none of which were used in the LCA – were used to characterize the resulting profile groups.ResultsWe accepted a 3-group solution, which we labeled High Wellbeing (65.3%), Low Cognition (20.3%), and Low Bio-Psychosocial (14.5%). Notably, the High Wellbeing group had significantly higher childhood IQ, lower Neuroticism scores, and a lower percentage of current smokers than the other 2 groups.ConclusionThe majority of individuals were functioning generally well; however, there was evidence of the presence of groups with different profiles, which may be explained in part in terms of cognitive ability differences. Results suggested that higher life-long intelligence, personality traits associated with less mental distress, and basic health practices such as avoiding smoking are important associates of wellbeing in old age.

Identification of Heterogeneous Cognitive Subgroups in Community-Dwelling Older Adults: A Latent Class Analysis of the Einstein Aging Study

OBJECTIVES The aim of this study was to identify natural subgroups of older adults based on cognitive performance, and to establish each subgroups characteristics based on demographic factors, physical function, psychosocial well-being, and comorbidity. METHODS We applied latent class (LC) modeling to identify subgroups in baseline assessments of 1345 Einstein Aging Study (EAS) participants free of dementia. The EAS is a community-dwelling cohort study of 70+ year-old adults living in the Bronx, NY. We used 10 neurocognitive tests and 3 covariates (age, sex, education) to identify latent subgroups. We used goodness-of-fit statistics to identify the optimal class solution and assess model adequacy. We also validated our model using two-fold split-half cross-validation. RESULTS The sample had a mean age of 78.0 (SD=5.4) and a mean of 13.6 years of education (SD=3.5). A 9-class solution based on cognitive performance at baseline was the best-fitting model. We characterized the 9 identified classes as (i) disadvantaged, (ii) poor language, (iii) poor episodic memory and fluency, (iv) poor processing speed and executive function, (v) low average, (vi) high average, (vii) average, (viii) poor executive and poor working memory, (ix) elite. The cross validation indicated stable class assignment with the exception of the average and high average classes. CONCLUSIONS LC modeling in a community sample of older adults revealed 9 cognitive subgroups. Assignment of subgroups was reliable and associated with external validators. Future work will test the predictive validity of these groups for outcomes such as Alzheimers disease, vascular dementia and death, as well as markers of biological pathways that contribute to cognitive decline. (JINS, 2018, 24, 511-523).

Abdominal obesity is a risk factor for dysexecutive function in chronic kidney disease.

The aim of this study was to assess the influence of the metabolic syndrome and its components on dysexecutive function (DF) in individuals with and without CKD. Among 588 participants aged over 70 from the Einstein Aging Study (EAS), we defined DF as performance of 2SDs below the mean on any one test or 1.5SDs below the mean on any two of the following: Block Design, Digit Symbol Coding and the Trail-making Tests A and B. We defined CKD as an eGFR below 60 mL/min/m2. MetS was defined according to recent guidelines from the National Cholesterol Education Program. 149 participants had CKD at cross-section, 16.1% of which also showed DF. Of the 439 participants without CKD, 12.3% displayed DF. Abdominal obesity as measured by waist circumference, was an independent risk factor for dysexecutive function in CKD (OR = 14.3, 95%CI = 2.21–91.93, p = 0.005) but not in non-CKD. None of the other MetS components were associated with DF. Results suggested that abdominal obesity, recognized as an integral part of the MetS, is a strong risk factor for DF in individuals with CKD.

Cognitive Impairment and Dementia in Older Adults with Chronic Kidney Disease: A Review

Individuals with chronic kidney disease (CKD), especially older adults, are at more risk of experiencing cognitive impairment, possibly leading to mild cognitive impairment and/or dementia. Studies report associations between CKD and cognitive impairment; although unclear, there seems to be a graded association between stage of CKD and affected cognitive domains, with executive function being affected earlier in the process than episodic memory and global ability. In CKD, dysexecutive mild cognitive impairment and vascular dementia are also more prominent than other subtypes. Explanations are directed toward traditional and nontraditional vascular factors, which may also explain or mediate the association between CKD and type of cognitive impairment. Future research is urged to focus on the longitudinal association between specific domains of cognitive function, including executive function and memory and CKD; to develop screening tools fit for every CKD stage in elderly individuals, and lastly, to use imaging methods that may help clarify the underlying mechanisms connecting the kidney and the brain.