Margaret Cadden

A review of cardiorespiratory fitness-related neuroplasticity in the aging brain

The literature examining the relationship between cardiorespiratory fitness and the brain in older adults has increased rapidly, with 30 of 34 studies published since 2008. Here we review cross-sectional and exercise intervention studies in older adults examining the relationship between cardiorespiratory fitness and brain structure and function, typically assessed using Magnetic Resonance Imaging (MRI). Studies of patients with Alzheimers disease are discussed when available. The structural MRI studies revealed a consistent positive relationship between cardiorespiratory fitness and brain volume in cortical regions including anterior cingulate, lateral prefrontal, and lateral parietal cortex. Support for a positive relationship between cardiorespiratory fitness and medial temporal lobe volume was less consistent, although evident when a region-of-interest approach was implemented. In fMRI studies, cardiorespiratory fitness in older adults was associated with activation in similar regions as those identified in the structural studies, including anterior cingulate, lateral prefrontal, and lateral parietal cortex, despite heterogeneity among the functional tasks implemented. This comprehensive review highlights the overlap in brain regions showing a positive relationship with cardiorespiratory fitness in both structural and functional imaging modalities. The findings suggest that aerobic exercise and cardiorespiratory fitness contribute to healthy brain aging, although additional studies in Alzheimers disease are needed.

Factors Associated with Employment Status in Individuals with Multiple Sclerosis

BACKGROUND Unemployment is common in individuals with multiple sclerosis (MS) and is associated with substantial socioeconomic burden. Several MS-related factors have been found to be associated with employment status, including fatigue, depression, cognitive problems, and motor difficulties. However, few studies have examined these factors collectively in predicting employment. The present study aimed to explore these variables together in predicting employment status in MS. METHODS Fifty-three individuals with MS participating in a research study of cognitive, emotional, and social factors related to MS were examined. Composite scores were created using factor analysis that represented cognition, fatigue, depression, and motor function. These composite scores, along with the Expanded Disability Status Scale score, were explored as predictors of employment status (working, not working) via logistic regression. Models of mediation were also investigated. RESULTS A model including composite scores of motor function, cognition, depression, and fatigue significantly distinguished those who are unemployed versus employed. However, only the cognitive, motor, and fatigue composite scores were found to be significantly associated with unemployment individually. RESULTS of a mediation analysis using 1000 bootstrap samples indicated that the cognitive and fatigue composite scores significantly mediated the effect of disability on work status. CONCLUSIONS Cognitive function and fatigue mediate the effect of MS disability on employment status. Interventions targeting cognitive difficulties and fatigue in MS may be effective in helping individuals maintain employment.

Physical Activity Is Positively Associated with Episodic Memory in Aging

Aging is associated with performance reductions in executive function and episodic memory, although there is substantial individual variability in cognition among older adults. One factor that may be positively associated with cognition in aging is physical activity. To date, few studies have objectively assessed physical activity in young and older adults, and examined whether physical activity is differentially associated with cognition in aging. Young (n=29, age 18-31 years) and older adults (n=31, ages 55-82 years) completed standardized neuropsychological testing to assess executive function and episodic memory capacities. An experimental face-name relational memory task was administered to augment assessment of episodic memory. Physical activity (total step count and step rate) was objectively assessed using an accelerometer, and hierarchical regressions were used to evaluate relationships between cognition and physical activity. Older adults performed more poorly on tasks of executive function and episodic memory. Physical activity was positively associated with a composite measure of visual episodic memory and face-name memory accuracy in older adults. Physical activity associations with cognition were independent of sedentary behavior, which was negatively correlated with memory performance. Physical activity was not associated with cognitive performance in younger adults. Physical activity is positively associated with episodic memory performance in aging. The relationship appears to be strongest for face-name relational memory and visual episodic memory, likely attributable to the fact that these tasks make strong demands on the hippocampus. The results suggest that physical activity relates to cognition in older, but not younger adults.

Memory integration in amnesia: Prior knowledge supports verbal short-term memory

Short-term memory (STM) and long-term memory (LTM) have traditionally been considered cognitively distinct. However, it is known that STM can improve when to-be-remembered information appears in contexts that make contact with prior knowledge, suggesting a more interactive relationship between STM and LTM. The current study investigated whether the ability to leverage LTM in support of STM critically depends on the integrity of the hippocampus. Specifically, we investigated whether the hippocampus differentially supports between-domain versus within-domain STM-LTM integration given prior evidence that the representational domain of the elements being integrated in memory is a critical determinant of whether memory performance depends on the hippocampus. In Experiment 1, we investigated hippocampal contributions to within-domain STM-LTM integration by testing whether immediate verbal recall of words improves in MTL amnesic patients when words are presented in familiar verbal contexts (meaningful sentences) compared to unfamiliar verbal contexts (random word lists). Patients demonstrated a robust sentence superiority effect, whereby verbal STM performance improved in familiar compared to unfamiliar verbal contexts, and the magnitude of this effect did not differ from that in controls. In Experiment 2, we investigated hippocampal contributions to between-domain STM-LTM integration by testing whether immediate verbal recall of digits improves in MTL amnesic patients when digits are presented in a familiar visuospatial context (a typical keypad layout) compared to an unfamiliar visuospatial context (a random keypad layout). Immediate verbal recall improved in both patients and controls when digits were presented in the familiar compared to the unfamiliar keypad array, indicating a preserved ability to integrate activated verbal information with stored visuospatial knowledge. Together, these results demonstrate that immediate verbal recall in amnesia can benefit from two distinct types of semantic support, verbal and visuospatial, and that the hippocampus is not critical for leveraging stored semantic knowledge to improve memory performance.

Beyond Binary: Exploring the Merits of Three Depression Groups in Multiple Sclerosis.

Objective: Depression has been traditionally explored in the context of multiple sclerosis (MS) as a binary construct (depressed, not depressed). However, given the 50% lifetime prevalence rate of depression in MS, it may be useful to consider not only currently depressed versus nondepressed patients, but to evaluate groups that better characterize the complexity of MS depression. The objective of the current study was to examine demographic, cognitive, illness, and psychosocial variables thought to associate with depression in MS across 3 groups: currently depressed, remitted depression, and never been depressed. Method: Fifty-four individuals with MS were examined. Current depression status was measured using the Beck Depression Inventory—Fast Screen (BDI-FS; Beck, Steer, & Brown, 2000). Past depression was evaluated using the Structured Clinical Interview for DSM–IV Disorders (SCID-IV; First, Spitzer, Gibbon, & Williams, 1998) and a semistructured psychosocial interview. Results: The results of the current study show that evaluating depression in 3 groups is useful for exploring risk, protective, and compensatory factors of depression in MS. A consistent grouping pattern (e.g., the remitted depression group always functioning the same as the never been depressed group) was not found among the variables examined; rather, several different patterns were observed. Several of these patterns revealed differences between the remitted depression and never been depressed groups; these differences would not have been observed had these 2 groups been combined into a “not currently depressed” group. Conclusions: These different patterns yield important information about the complex relationships of depression in MS that may be obscured when depression is viewed as a binary construct.

Cognitive Reserve Attenuates the Effect of Disability on Depression in Multiple Sclerosis

OBJECTIVE The current study explored the moderating role of cognitive reserve on the relationship between disability and depression in a sample of individuals in which brain pathology is thought to contribute to depression (multiple sclerosis; MS). METHOD Fifty-four individuals with MS were examined. Depression was measured using the Beck Depression Inventory-Fast Screen (BDI-FS). In addition to collecting demographic (education) and disease burden (Expanded Disability Status Scale; EDSS) related variables, participants completed a neuropsychological test battery and psychosocial questionnaires. Cognitive reserve (CR) was conceptualized in two ways: Fixed CR and Malleable CR. Fixed CR was measured using years of education and crystallized intelligence (Shipley Vocabulary). Malleable CR was operationalized as a composite of measures from the Cognitive Heath Questionnaire (CHQ). Two regressions on depression (BDI-FS) examining either type of cognitive reserve, EDSS, and their interactions were explored. Results: The interaction between EDSS and both conceptualizations of cognitive reserve were significant, t(50) = -2.60, p = .013, PRE = .12 (Fixed CR); t(47) = -2.02, p = .049, PRE = .08 (Malleable CR). Simple effects testing revealed the same pattern regardless of the type of cognitive reserve examined; EDSS predicted depression only in those with low cognitive reserve. CONCLUSIONS Cognitive reserve moderates the relationship between disability and depression in MS; disability does not appear to influence depression in those with high cognitive reserve.

Psychological and Behavioral Therapies in Multiple Sclerosis

Depression in multiple sclerosis (MS) is very common, with a lifetime prevalence of around 50 %, which is much higher than the 8 % reported for the general population. In this chapter, we explore some of the psychological and behavioral depression treatments that have been studied in MS. Our review shows clearly that depression in MS is treatable, via both psychotherapeutic and behavioral interventions. Randomized clinical trials (RCTs) on psychotherapy have generally revealed very large effect sizes, with the one benchmarking study (one that examines treatment as it actually occurs in clinical settings) in the literature showing a still large but somewhat smaller effect size than RCTs. Exercise appears to be a promising potential treatment of depression in MS and has been shown to be correlated with lower depression. Additionally, RCTs of exercise have revealed small to moderate effect sizes on reducing depression. One problem with psychological and behavioral treatments of depression in MS is the salience of disability and travel issues that make involvement in such intensive treatment more challenging. Thus, even though treatments are often effective, patients may avoid them in favor of other interventions. Telephone-based interventions have been shown to be very effective in treating depression in MS and could represent a promising approach that circumvents such obstacles. Even though current treatments are effective, future research should explore why nearly half of patients do not respond to available treatments. A focus on the possibility that co-morbid conditions (e.g., anxiety or personality disorders) could interfere with standard depression treatments, as well as possible mediators of treatment (e.g., fatigue, disability levels, sleep disturbance), may be promising avenues for future research.