Dynamic associations between glucose and ecological momentary cognition in Type 1 Diabetes.

Type 1 diabetes (T1D) is a chronic condition characterized by glucose fluctuations. Laboratory studies suggest that cognition is reduced when glucose is very low (hypoglycemia) and very high (hyperglycemia). Until recently, technological limitations prevented researchers from understanding how naturally-occurring glucose fluctuations impact cognitive fluctuations. This study leveraged advances in continuous glucose monitoring (CGM) and cognitive ecological momentary assessment (EMA) to characterize dynamic, within-person associations between glucose and cognition in naturalistic environments. Using CGM and EMA, we obtained intensive longitudinal measurements of glucose and cognition (processing speed, sustained attention) in 200 adults with T1D. First, we used hierarchical Bayesian modeling to estimate dynamic, within-person associations between glucose and cognition. Consistent with laboratory studies, we hypothesized that cognitive performance would be reduced at low and high glucose, reflecting cognitive vulnerability to glucose fluctuations. Second, we used data-driven lasso regression to identify clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations. Large glucose fluctuations were associated with slower and less accurate processing speed, although slight glucose elevations (relative to person-level means) were associated with faster processing speed. Glucose fluctuations were not related to sustained attention. Seven clinical characteristics predicted individual differences in cognitive vulnerability to glucose fluctuations: age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and neck circumference. Results establish the impact of glucose on processing speed in naturalistic environments, suggest that minimizing glucose fluctuations is important for optimizing processing speed, and identify several clinical characteristics that may exacerbate cognitive vulnerability to glucose fluctuations.

Memory and mental status correlates of modified Braak staging.

We assessed the relationships of performance on memory and mental status tests and neuropathologic stage of Alzheimer's disease as defined by Braak and Braak in 29 patients from a prospective clinicopathologic series. We predicted that memory changes would occur at an earlier Braak stage than mental status changes. Staging was accomplished by matching the topographic distribution of neurofibrillary lesions detected with tau immunocytochemistry to the best fitting diagram published by Braak and Braak. Higher Braak stages were associated with decrements in performance on both memory and mental status tests. As predicted, memory performance declined from stages II to III and mental status did not decline until stages III to IV. The association between memory and Braak stage was unchanged after adjusting for neocortical senile plaques, whereas adjustments for Braak stage eliminated the association between cognitive functioning and amyloid burden. We conclude that Braak staging provides a useful summary of Alzheimer's disease neuropathology, which is associated with both memory and mental status performance.

Diagnosis of early dementia by the Double Memory Test: encoding specificity improves diagnostic sensitivity and specificity.

OBJECTIVE: To compare the Double Memory Test (DMT) with standard memory tests in the diagnosis of early dementia. BACKGROUND: Diagnosis of dementia requires memory impairment, but few memory tests coordinate acquisition and retrieval to optimize encoding specificity for high sensitivity and specificity. The DMT was developed to improve early diagnosis. DESIGN: We compared the discriminative validity of the DMT, Paired Associates (PA), and Logical Memory (LM) memory tests in a nested case-control study of 30 cases of early dementia and 90 controls matched for age, education, and sex. METHODS: The DMT includes memory tests with (CCR) and without (ICR) encoding specificity. Both tests use category cues to elicit retrieval, but CCR optimizes encoding specificity because the same cues are used for acquisition and retrieval. ICR does not because category cues are used only for retrieval. We used conditional logistic regression to estimate diagnostic sensitivity and specificity. RESULTS: The median BIMC of dementia cases was 10, indicating mild dementia. CCR had much higher sensitivity (93%) and specificity (99%) than ICR (53%, 94%), PA (68%, 91%), and LM (48%, 92%). CCR had the greatest advantage in the mildest cases. CONCLUSIONS: CCR has substantially higher sensitivity and specificity for diagnosis of early dementia than memory tests that do not coordinate acquisition and retrieval. Superior discrimination by CCR is due to an encoding specificity deficit in dementia that increases the difference in recall by cases and controls. CCR is an efficient test with excellent discriminative validity that should facilitate diagnosis of early dementia.

Screening for dementia with the memory impairment screen.

OBJECTIVES: To validate a sensitive and specific screening test for AD and other dementias, assess its reliability and discriminative validity, and present normative data for its use in various applied settings. BACKGROUND: To improve discrimination in screening for AD and dementia, we developed the Memory Impairment Screen (MIS), a 4-minute, four-item, delayed free- and cued-recall test of memory impairment. The MIS uses controlled learning to ensure attention, induce specific semantic processing, and optimize encoding specificity to improve detection of dementia. METHODS: Equivalent forms of the MIS were given at the beginning and end of the testing session to assess alternate forms reliability. Discriminative validity was assessed in a criterion sample of 483 aged individuals, 50 of whom had dementia according to Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised) criteria. RESULTS: The MIS had good alternate forms reliability, high construct validity for memory impairment, and good discriminative validity in terms of sensitivity, specificity, and positive predictive value. We present normative data for use in settings with different base rates (prevalences) of AD and dementia. CONCLUSION: The MIS provides efficient, reliable, and valid screening for AD and other dementias.

Constraints on general slowing: a meta-analysis using hierarchical linear models with random coefficients.

General slowing (GS) theories are often tested by meta-analysis that model mean latencies of older adults as a function of mean latencies of younger adults. Ordinary least squares (OLS) regression is inappropriate for this purpose because it fails to account for the nested structure of multitask response time (RT) data. Hierarchical linear models (HLM) are an alternative method for analyzing such data. OLS analysis of data from 21 studies that used iterative cognitive tasks supported GS; however, HLM analysis demonstrated significant variance in slowing across experimental tasks and a process-specific effect by showing less slowing for memory scanning than for visual-search and mental-rotation tasks. The authors conclude that HLM is more suitable than OLS methods for meta-analyses of RT data and for testing GS theories.

Understanding Ageing. An evaluation of research designs for assessing the interdependence of ageing-related changes.

BACKGROUND: Cross-sectional studies of samples varying widely in age have found moderate to high levels of shared age-related variance among measures of cognitive and physiological capabilities, leading researchers to posit common factors or common causal influences for diverse age-related phenomenon. OBJECTIVE: The influence of population average changes with age on cross-sectional estimates of association has not been widely appreciated in developmental and ageing research. Covariances among age-related variables in cross-sectional studies are highly confounded in regards to inferences about associations among rates of change within individuals since covariances can result from a number of sources including average population age-related differences (fixed age effects) in addition to initial individual differences and individual differences in rates of ageing (random age effects). Analysis of narrow age-cohort samples may provide a superior analytical basis for testing hypotheses regarding associations between rates of change in cross-sectional studies. CONCLUSIONS: The use of age-heterogeneous cross-sectional designs for evaluating interdependence of ageing-related processes is discouraged since associations will not necessarily reflect individual-level correlated rates of change. Typical cross-sectional studies do not provide sufficient evidence for the interdependence of ageing-related changes and should not serve as the basis for theories and hypotheses of ageing. Reanalyzing existing cross-sectional studies using a sequential narrow-age cohort approach provides a useful alternative for evaluating associations between ageing-related changes. Longitudinal designs, however, provide a much stronger basis for inference regarding associations between rates of ageing within individuals.

Dual-task performance in demented and nondemented elderly.

The present study examined the ability of demented and nondemented elderly subjects to divide their attention between recalling digits and judging the similarity of pairs of letters. Both groups showed substantial decrements in digit recall following distraction by letter matching. To identify the nature of the interference effect, digit recall was scored according to a strict criterion where preservation of the serial order of the digits was required (order-based recall), and a lenient criterion where preservation of digit order was not required (order-free recall). While both groups showed a comparable decrement in order-based recall due to the interfering task, order-free recall virtually eliminated the decrement for the nondemented group whereas substantial interference was still observed in the demented group. These results suggest that letter matching interferes with digit recall in nondemented elderly primarily by disrupting order information. In the case of demented elderly, letter matching disrupts the preservation of item information as well.

Utility of the dexamethasone suppression test in the diagnosis of poststroke depression.

The utility of the dexamethasone suppression test (DST) in the diagnosis of depression was examined in an outpatient sample of 29 stroke patients. Results indicated that the DST's sensitivity was 15%, its specificity was 67%, and its positive predictive value was 48%. These findings suggest that the DST yields no more information than would be gained from random assignment of the diagnosis of depression. Therefore, it is not a useful measure of mood in these patients.

Pathological markers associated with normal aging and dementia in the elderly.

We investigated the associations of pathological markers of Alzheimer's disease (AD) and diffuse Lewy body disease as well as possible markers of vascular dementia with cognitive function in a sample of 20 nondemented and 35 demented subjects (median age of both groups, 88 years) who had been studied prospectively for 4.0 +/- 2.1 years. Very old demented subjects almost always had nonneuritic senile plaques, but over half had no neuritic senile plaques and little other AD pathology. Five subjects had cortical Lewy bodies; all were demented. We propose that hippocampal sclerosis, leukoencephalopathy, and multiple lacunae are possible markers of vascular dementia. When grouped together, these markers were significantly associated with dementia and occurred in 40% of demented subjects. As the relative frequency of neuritic markers of AD (and possibly AD itself) declines in the tenth decade, vascular dementia may become an increasingly important type of dementia.