Stuart W. S. MacDonald

Intra-individual variability in behavior: links to brain structure, neurotransmission and neuronal activity

Intra-individual variability reflects a transient, within-person change in behavioral performance. It is a common component of aging-related cognitive decline and the behavioral changes associated with neurodegenerative and other brain-related disorders such as traumatic brain injury and schizophrenia. Behavioral changes within an individual can reflect alterations at a systems or a cellular level in the brain, and monitoring intra-individual variability can therefore provide a warning of underlying pathology. Despite frequent reports of intra-individual variability, there is little synthesis, and no direct examination of the neural underpinnings. Here, we integrate seminal findings from cognitive research across lifespans of individuals, and also neuropsychological and neurobiological findings, to identify key questions and some potential answers, and to set challenges for fostering future research into intra-individual variability.

Intraindividual variability in cognitive performance in older adults: comparison of adults with mild dementia, adults with arthritis, and healthy adults.

Intraindividual variability in latency and accuracy of cognitive performance across both trials and occasions was examined in 3 groups of older adults: healthy adults, adults with arthritis, and adults diagnosed with mild dementia. Participants completed 2 reaction-time and 2 episodic-memory tasks on 4 occasions. Results indicated that intraindividual variability in latency was greater in individuals diagnosed with mild dementia than in adults who were neurologically intact, regardless of their health status. Individual differences in variability were stable over time and across cognitive domains. Intraindividual variability was also related to level of performance and was uniquely predictive of neurological status, independent of level of performance. Results suggest that intraindividual variability may be a behavioral indicator of compromised neurological mechanisms.

Performance variability is related to change in cognition: evidence from the Victoria Longitudinal Study.

Performance variability across repeated task administrations may be an important indicator of age-related cognitive functioning. In the present investigation, the authors examined whether age differences and change in inconsistency were related to 6-year (3 occasion) cognitive change. Inconsistency scores were computed from 4 reaction time tasks performed by 446 older adults (54-89 years). Replicating previous cross-sectional results, greater inconsistency was observed for older participants even after controlling for differences in response speed. New longitudinal results demonstrated (a) associations between inconsistency at baseline measurement and 6-year change in cognitive performance; (b) longitudinal change in inconsistency; and (c) intraindividual covariation between 6-year change in inconsistency and 6-year change in level of cognitive function. These findings support the view that performance variability serves as a marker of cognitive aging.

Moment-to-moment brain signal variability: a next frontier in human brain mapping?

Neuroscientists have long observed that brain activity is naturally variable from moment-to-moment, but neuroimaging research has largely ignored the potential importance of this phenomenon. An emerging research focus on within-person brain signal variability is providing novel insights, and offering highly predictive, complementary, and even orthogonal views of brain function in relation to human lifespan development, cognitive performance, and various clinical conditions. As a result, brain signal variability is evolving as a bona fide signal of interest, and should no longer be dismissed as meaningless noise when mapping the human brain.

Latent Change Models of Adult Cognition: Are Changes in Processing Speed and Working Memory Associated With Changes in Episodic Memory?

The authors used 6-year longitudinal data from the Victoria Longitudinal Study (VLS) to investigate individual differences in amount of episodic memory change. Latent change models revealed reliable individual differences in cognitive change. Changes in episodic memory were significantly correlated with changes in other cognitive variables, including speed and working memory. A structural equation model for the latent change scores showed that changes in speed and working memory predicted changes in episodic memory, as expected by processing resource theory. However, these effects were best modeled as being mediated by changes in induction and fact retrieval. Dissociations were detected between cross-sectional ability correlations and longitudinal changes. Shuffling the tasks used to define the Working Memory latent variable altered patterns of change correlations.

Education Does Not Slow Cognitive Decline with Aging: 12-Year Evidence from the Victoria Longitudinal Study

Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Fewer studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1014 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range, 54-95 years) and gender, we found that years of education (range, 6-20 years) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging.

Neurocognitive markers of cognitive impairment: exploring the roles of speed and inconsistency.

A well-known challenge for research in the cognitive neuropsychology of aging is to distinguish between the deficits and changes associated with normal aging and those indicative of early cognitive impairment. In a series of 2 studies, the authors explored whether 2 neurocognitive markers, speed (mean level) and inconsistency (intraindividual variability), distinguished between age groups (64-73 and 74-90+ years) and cognitive status groups (nonimpaired, mildly impaired, and moderately impaired). Study 1 (n = 416) showed that both level and inconsistency distinguished between the age and 2 cognitive status (not impaired, mildly impaired) groups, with a modest tendency for inconsistency to predict group membership over and above mean level. Study 2 (n = 304) replicated these results but extended them because of the qualifying effects associated with the unique moderately impaired oldest group. Specifically, not only were the groups more firmly distinguished by both indicators of speed, but evidence for the differential contribution of performance inconsistency was stronger. Neurocognitive markers of speed and inconsistency may be leading indicators of emerging cognitive impairment.Supervisory Committee Dr. Kimberly Kerns, Department of Psychology Supervisor Dr. Mauricio Garcia-Barrera, Department of Psychology Departmental Member – Revision Supervisor Dr. John Walsh, Department of Educational Psychology and Leadership Studies External Member Dr. Leslie Saxon, Department of Linguistics Additional Member Abstract The purpose of the current study was to examine the impact of working memory on speech monitoring processes in the primary language of school-age children using the framework of Levelt’s Perceptual Loop Theory of speech production (1983). A community sample of eight children aged 6-8 and fourteen children aged 10-12 completed 4 verbal description tasks under different conditions; control, working memory load, white noise and combined working memory load and white noise. Participants also completed measures of listening span, digit span and spatial span. The results indicate that with increasing working memory load, children make significantly more speech errors, silent pauses and repetitions. No relationship was found between working memory and total repairs per errors or between working memory and total number of editing terms used. Group differences across the conditions were not significant; however, age-related trends were notable. Younger children had greater difficulty monitoring their speech with the introduction of working memory load; whereas, older children had greater difficulty with the introduction of white noise. A revised speech production model incorporating aspects of working memory is recommended and implications for clinical populations are discussed.The purpose of the current study was to examine the impact of working memory on speech monitoring processes in the primary language of school-age children using the framework of Levelt’s Perceptual Loop Theory of speech production (1983). A community sample of eight children aged 6-8 and fourteen children aged 10-12 completed 4 verbal description tasks under different conditions; control, working memory load, white noise and combined working memory load and white noise. Participants also completed measures of listening span, digit span and spatial span. The results indicate that with increasing working memory load, children make significantly more speech errors, silent pauses and repetitions. No relationship was found between working memory and total repairs per errors or between working memory and total number of editing terms used. Group differences across the conditions were not significant; however, age-related trends were notable. Younger children had greater difficulty monitoring their speech with the introduction of working memory load; whereas, older children had greater difficulty with the introduction of white noise. A revised speech production model incorporating aspects of working memory is recommended and implications for clinical populations are discussed.

Self-awareness after traumatic brain injury: A comparison of measures and their relationship to executive functions

Poor awareness of deficit is common after brain injury. Recent literature has examined various tools for measurement of this phenomenon; the most widely used being self-other rating scales. Although self-other scale measures have face validity, their criterion-related validity has not been adequately demonstrated, and there is little information as to whether and how they relate to other neuropsychological measures. The present study compared measurement of awareness by the Dysexecutive (DEX) Questionnaire self-other rating scale with the Self-Awareness of Deficits Interview (SADI), a semistructured interview measure. Evaluation of awareness by these measures was compared to tests of executive functioning and IQ. Results indicated significant, albeit marginal relationships between the two measures, and better correlation of the SADI with measures of frontal lobe functioning. The SADI also predicted injury severity.

The association between endogenous free testosterone and cognitive performance : A population-based study in 35 to 90 year-old men and women

The relationship between testosterone (T) and cognition has yielded conflicting evidence, showing both positive and negative influences of T on cognitive performance. The association between free testosterone (FT) and cognition was revisited in a large population-based sample of 1276 women and 1107 men (35-90 years of age), assessed individually on visuospatial, verbal fluency, semantic, and episodic memory tasks. For men, higher FT levels were associated with better visuospatial abilities, semantic memory, and episodic memory, with greater positive influence with increasing age. Statistical covariates included age, education, and select medications. For women, FT was negatively associated with verbal fluency, semantic memory, and episodic memory, although only verbal fluency was significant at conventional alpha levels. These results support the claim that FT exerts sex-specific influences on cognitive performance.

Serum total cholesterol, statins and cognition in non-demented elderly

BACKGROUND The association between serum total cholesterol (TC), lipid-lowering drugs and cognition in the elderly is currently controversial. OBJECTIVE To investigate the relationship between TC, lipid-lowering drugs and cognitive functions in non-demented elderly. DESIGN AND SETTING Participants of the Cardiovascular risk factors, aging and dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982 or 1987. Analyses are based on 1382 non-demented participants re-examined in 1998 after an average follow-up of 21 years. RESULTS High midlife TC was associated with poorer late-life episodic memory and category fluency. TC decreased in most individuals over time. A more pronounced decrease was related to poorer late-life episodic memory and psychomotor speed, but not if subjects used statins. CONCLUSIONS The TC-cognition relationship seems bidirectional. High midlife TC is associated with poorer late-life cognition, but decreasing TC after midlife may reflect poorer cognitive status. Statins may be beneficial for cognition in non-demented elderly.