Cognitive Profiles of Aging in Multiple Sclerosis.

BACKGROUND: Increasingly favorable mortality prognosis in multiple sclerosis (MS) raises questions regarding MS-specific cognitive aging and the presence of comorbidities such as Alzheimer's disease (AD). OBJECTIVE: To assess elderly with MS (EwMS) and age-matched healthy controls (HCs) using both MS- and AD-specific psychometrics. METHODS: EwMS (n = 104) and 56 HCs were assessed on a broad spectrum of language, visual-spatial processing, memory, processing speed, and executive function tests. Using logistic regression analysis, we examined cognitive performance differences between the EwMS and HC groups. Cognitive impairment (CI) was defined using a -1.5 SD threshold relative to age and education years-matched HCs, in two cognitive domains. RESULTS: CI was observed in 47.1% of EwMS with differences most often seen on tests emphasizing cognitive processing speed as measured by Symbol Digit Modalities Test (SDMT) (d = 0.9, p < 0.001) and verbal fluency (both category-based d = 0.87, p < 0.001; letter-based d = 0.67, p < 0.001). After adjusting for age, sex and years of education, MS/HC diagnosis was best predicted (R 2 = 0.27) by differences in category-based verbal fluency (Wald = 9.935, p = 0.002) and SDMT (Wald = 13.937, p < 0.001). CONCLUSION: This study confirms the common hallmark of slowed cognitive processing speed in MS among elderly patients. Defective verbal fluency, less often observed in younger cohorts, may represent emerging cognitive pathology due to other etiologies.

Health risk prediction models incorporating personality data: Motivation, challenges, and illustration.

The age of "big data" in health has ushered in an era of prediction models promising to forecast individual health events. Although many models focus on enhancing the predictive power of medical risk factors with genomic data, a recent proposal is to augment traditional health predictors with psychosocial data, such as personality measures. In this article we provide a general overview of the medical risk prediction models and then discuss the rationale for integrating personality data. We suggest three principles that should guide work in this area if personality data is ultimately to be useful within risk prediction as it is actually practiced in the health care system. These include (a) prediction of specific, priority health outcomes; (b) sufficient incremental validity beyond established biomedical risk factors; and (c) technically responsible model-building that does not overfit the data. We then illustrate the application of these principles in the development of a personality-augmented prediction model for the occurrence of mild cognitive impairment, designed for a primary care setting. We evaluate the results, drawing conclusions for the direction an iterative, programmatic approach would need to take to eventually achieve clinical utility. Although there is great potential for personality measurement to play a key role in the coming era of risk prediction models, the final section reviews the many challenges that must be faced in real-world implementation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Preliminary investigation of cognitive function in aged multiple sclerosis patients: Challenges in detecting comorbid Alzheimer's disease.

BACKGROUND: Cognitive impairment can be seen in patients of all ages with multiple sclerosis (MS). However, there is limited research on neurocognitive disorder in older adults with MS and how to detect Alzheimer's disease (AD) or its prodromal stage, amnestic mild cognitive impairment (aMCI). Thus, the MS clinician is challenged to discriminate between signs of MS-related cognitive decline versus a secondary neurodegenerative process. OBJECTIVE: Compare cognition in older MS patients to patients with AD and aMCI. METHODS: We evaluated cognitively impaired and unimpaired MS patients, AD patients, aMCI patients, and healthy controls (HCs), all elderly (n = 20 per group). AD and aMCI diagnoses were derived by consensus conference independent of the MS research project. Neuropsychological measures assessed domains commonly affected in AD, including verbal memory and expressive language. RESULTS: Cognitively impaired and unimpaired MS groups did not differ on any measures sensitive to AD. Unimpaired MS patients were comparable to HCs. Impaired MS patients showed decreased semantic fluency, similar to aMCI patients. Lastly, while both AD and aMCI groups had deficient memory retention, there was no evidence of a retention deficit in either MS group. CONCLUSION: Our findings suggest that the cognitive profiles of MS and AD are distinct. In contrast to AD, MS is not associated with impairment of memory consolidation. However, there may be overlap between cognitive deficits related to MS and aMCI. Thus, evidence of poor memory retention, in an older MS patient may merit comprehensive dementia evaluation. The study is preliminary and includes no AD biomarkers (e.g., amyloid imaging) to confirm or rule out AD pathology.

Longitudinal personality change associated with cognitive decline in multiple sclerosis.

We previously reported that personality and cognition were stable over 3 years in patients with multiple sclerosis (MS). This study examined whether a longer duration would reveal evidence of emerging personality dysfunction. The NEO Five-Factor Inventory and Brief International Cognitive Assessment for MS was used to assess personality and cognition, respectively. Patients were classified as "Cog Stable" or "Cog Decline" based on cognitive deterioration over 5 years. Extraversion and Conscientiousness declined across pooled groups. Follow-up of a group by time interaction found that decline in these traits was more evident in the Cog Decline group, demonstrating a link between personality and cognitive change.

Apolipoprotein E genotype impact on memory and attention in older persons: the moderating role of personality phenotype.

OBJECTIVES: To determine if phenotypic personality traits modify the association of Apolipoprotein E (APOE) genotypes with different domains of cognitive function. DESIGN: Cross-sectional. METHODS: 172 non-demented older adults were administered the NEO-Five Factor Inventory (NEO-FFI), a battery of neuropsychological tests assessing memory, attention, executive function, language, and visuospatial ability, and underwent APOE genotyping. Multivariate (multiple-dependent variable) regression models predicting cognitive domains tested APOE interactions with personality traits, adjusting for age, sex, and education. RESULTS: The APOE ε4 allele showed small to modest main effects on memory and executive function (1/3 SD deficits for carriers, p < .05), with ε2 status evidencing minimal and non-significant benefit. Neuroticism interacted with both ε2 and ε4 alleles in associations with attention scores (p = .001), with ε2 benefits and ε4 deficits being marked at high Neuroticism (Mean [M] covariate-adjusted Z-score = .39 for ε2, -.47 for ε4). The association of ε4 with memory was moderated by Conscientiousness (p < .001), such that ε4 memory deficits were apparent at low Conscientiousness (M = -.56), but absent at high levels of Conscientiousness. Weaker patterns (p < .05) also suggested ε4-related detriments in executive function only at lower Conscientiousness, and ε2 memory benefits only at higher Openness. CONCLUSIONS: Conscientiousness and Neuroticism moderate APOE associations with memory and executive function. As such, they may be useful phenotypic markers in refining the prognostic significance of this polymorphism. Effect-modifying personality traits also provide clues about behavioral and psychological factors that influence the cognitive impact of APOE. Copyright © 2017 John Wiley & Sons, Ltd.

Trait neuroticism, extraversion, and conscientiousness in multiple sclerosis: Link to cognitive impairment?

BACKGROUND: Previous research suggests that patients with multiple sclerosis (MS) have higher neuroticism, lower extraversion, and lower conscientiousness relative to healthy controls (HCs). However, the prevalence of this maladaptive profile in MS and its relation to cognition is unknown. OBJECTIVE: Determine prevalence of maladaptive personality among MS patients, compared to HCs, and examine how it relates to cognitive dysfunction. METHODS: A sample of 275 MS patients and 55 HCs completed neuroperformance measures of information processing speed and memory. Self and informant ratings were obtained on the NEO Five-Factor Inventory. RESULTS: MS patients had higher neuroticism and lower extraversion than HCs. Cognitively impaired patients were also lower in conscientiousness. Cluster analysis revealed a configuration of these same three traits, representing a maladaptive profile. This profile was found in 50% of the overall MS sample, compared to 24% of HCs. However, only cognitively impaired MS patients had a higher prevalence of maladaptive personality compared to HCs. Among cognitively impaired patients, those with maladaptive traits were impaired in more cognitive domains than those with more adaptive traits. CONCLUSION: Cognitively impaired MS patients have a higher prevalence of seemingly maladaptive traits compared to HCs, demonstrating an association between cognition and personality in MS.

Hippocampus-dependent spatial learning is associated with higher global cognition among healthy older adults.

Cognitive deficits in normal aging have been associated with atrophy of the hippocampus. As such, methods to detect early dysfunction of the hippocampus have become valuable, if not indispensable, to early intervention. The hippocampus is critical for spatial memory and is among the first structures to atrophy with aging. Despite the presence of navigation deficits in aging, few studies have looked at the association between wayfinding ability, navigation strategies, general cognitive function, and hippocampal volume. In the current study we investigated whether better general cognitive function is associated with the use of hippocampal-dependent spatial strategies, better spatial memory, and increased hippocampal volume. We also investigated, within older adults, the effects of aging on spatial memory. Healthy older adults (N = 107) were tested on a virtual wayfinding task and a dual-solution navigation task that can be solved using either a hippocampal-dependent spatial strategy or a caudate nucleus-dependent response strategy. Participants were also administered the Montreal Cognitive Assessment (MoCA), a test that measures general cognition and is sensitive to dementia. A structural MRI was administered to a sub-set of participants (n = 49) and hippocampal volume was calculated using a Multiple Automatically Generated Templates (MAGeT) Brain algorithm. We found that age was negatively associated with wayfinding ability and hippocampal volume. On the wayfinding task, participants with higher MoCA scores found more target locations and travelled shorter distances. We also found a significant association between higher MoCA scores and spatial strategy use. MoCA scores, spatial memory ability, and spatial strategy use all positively correlated with a larger hippocampal volume. These results confirm that with age there is a decrease in spatial memory, which is consistent with decreased volume in the hippocampus with aging. Furthermore, better general cognitive function is associated with better wayfinding ability and increased use of hippocampal-dependent spatial strategies.

Personality and Performance in Specific Neurocognitive Domains Among Older Persons.

OBJECTIVE: Certain Big 5 personality dimensions have been repeatedly linked to global measures of cognitive function and outcome categories. We examined whether the Big 5 or their specific components showed differential evidence of associations with specific neurocognitive domains. METHODS: Participants were 179 older adults (70+) from a broader study on cognitive aging. The NEO-Five Factor Inventory and a comprehensive battery of neuropsychological tests were used. RESULTS: Adjusted for age, gender, and years of education, probability values, Bayes Factors, and measures effect size from linear models suggested strong evidence for associations between better delayed recall memory and higher Conscientiousness (principally the facets of Goal-Striving and Dependability) and Openness (specifically the Intellectual Interest component). Better executive function and attention showed moderate to strong evidence of associations with lower Neuroticism (especially the Self-conscious Vulnerability facet) and higher Conscientiousness (mostly the Dependability facet). Better language functioning was linked to higher Openness (specifically, the Intellectual Interests facet). Worse visual-spatial function was strongly associated with higher Neuroticism. CONCLUSION: Different tests of neurocognitive functioning show varying degrees of evidence for associations with different personality traits. Better understanding of the patterning of neurocognitive-personality linkages may facilitate grasp of underlying mechanisms and/or refine understanding of co-occurring clinical presentation of personality traits and specific cognitive deficits.

Differential effects of aging on motor and cognitive functioning in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) patients are impaired in motor and cognitive performance, but the extent to which these deficits are magnified by aging is unknown. In one prior study, differences in cognitive processing speed between MS patients and healthy individuals were of similar magnitude across the lifespan. Here, we have improved on this work by expanding assessment to multiple cognitive domains and motor functioning. OBJECTIVE: To determine whether the degree of cognitive and motor dysfunction in MS is magnified with increasing age. METHODS: In all, 698 MS patients (aged 29-71 years) and 226 healthy controls (HCs; aged 18-72 years) completed neuroperformance tests covering ambulation, upper extremity function, information processing speed, and memory. RESULTS: Linear regression models predicting cognitive and motor function revealed main effects of MS/HC diagnosis, age, and education across all measures. There was also an interaction between age and diagnosis on measures of motor function, but not on cognitive outcomes. CONCLUSION: The progression of motor decline is amplified by aging in MS. However, the degree of cognitive impairment does not vary across the lifespan. Thus, evidence of accelerated cognitive impairment in older adults with MS may signal the presence of other age-related cognitive pathologies.

Executive Function and Personality Predict Instrumental Activities of Daily Living in Alzheimer Disease.

OBJECTIVE: Previous research shows that executive function (EF) and personality independently predict functional decline. Our objective was to determine whether personality traits predict independence with instrumental activities of daily living (IADLs), after accounting for executive dysfunction, in a mixed sample of patients with amnestic mild cognitive impairment (MCI) and Alzheimer disease (AD). METHODS: In a cross-sectional analysis at a university medical center, 63 healthy older adults (median age: 67.6 years; 71% women) and 119 patients (median age: 75.0 years; 58% women) with varying degrees of AD (probable AD: 85; possible AD: 3; amnestic MCI: 31) were studied. Standardized neuropsychological measures, NEO Five-Factor Inventory (NEO-FFI), and informant-report Lawton and Brody IADL scales were used. All participants underwent neuropsychological evaluation, including administration of self- and informant-report NEO-FFI. Patients additionally underwent neurologic examination, and their informants completed the Lawton and Brody IADL scale. RESULTS: When testing the association between EF and personality on IADLs in the patient sample, conceptual card sorting, informant-report Openness, and informant-report Conscientiousness all significantly predicted IADLs, after accounting for age, education, and depression. In addition, a significant interaction showed that low Conscientiousness and executive dysfunction, in combination, can predict impairment of IADLs. CONCLUSION: Personality has a unique association with IADLs in patients with AD pathology that is not explained by EF. The findings confirm prior speculation that personality, in addition to cognitive dysfunction, is a risk factor for functional decline. Early identification of vulnerable individuals may allow for intervention to prolong functional independence.

Synergistic Effects of Reserve and Adaptive Personality in Multiple Sclerosis.

OBJECTIVES: Cognitive reserve moderates the effects of gray matter (GM) atrophy on cognitive function in neurological disease. Broadly speaking, Reserve explains how persons maintain function in the face of cerebral injury in cognitive and other functional domains (e.g., physical, social). Personality, as operationalized by the Five Factor Model (FFM), is also implicated as a moderator of this relationship. It is conceivable that these protective mechanisms are related. Prior studies suggest links between Reserve and personality, but the degree to which these constructs overlap and buffer the clinical effects of neuropathology is unclear. METHODS: We evaluated Reserve and FFM traits-Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness-in a cohort of 67 multiple sclerosis (MS) patients. We also examined the extent to which FFM traits and aspects of Reserve interact in predicting cognitive processing speed. RESULTS: Retrospectively reported educational/occupational achievement was associated with higher Openness, and childhood social engagement was associated with higher Extraversion, Agreeableness, and Conscientiousness. Current involvement in exercise activities and social activities was associated with Extraversion, current involvement in hobbies was associated with Neuroticism, and current receptive behaviors were associated with Agreeableness and Conscientiousness. When tested as predictors, Conscientiousness and childhood enrichment activities interacted in predicting cognitive processing speed after accounting for age, disease duration, disability, and GM volume. CONCLUSIONS: Childhood enrichment activities and Conscientiousness have a synergistic effect on cognitive processing speed. Current findings have implications for using psychological interventions to foster both Reserve and adaptive personality characteristics to stave off clinical symptoms in MS. (JINS, 2016, 22, 920-927).

Effects of dividing attention on memory for declarative and procedural aspects of tool use.

Tool-related knowledge and skills are supported by a complex set of memory processes that are not well understood. Some aspects of tools are mediated by either declarative or procedural memory, while other aspects may rely on an interaction of both systems. Although motor skill learning is believed to be primarily supported by procedural memory, there is debate in the current literature regarding the role of declarative memory. Growing evidence suggests that declarative memory may be involved during early stages of motor skill learning, although findings have been mixed. In the current experiment, healthy, younger adults were trained to use a set of novel complex tools and were tested on their memory for various aspects of the tools. Declarative memory encoding was interrupted by dividing attention during training. Findings showed that dividing attention during training was detrimental for subsequent memory for tool attributes as well as accurate demonstration of tool use and tool grasping. However, dividing attention did not interfere with motor skill learning, suggesting that declarative memory is not essential for skill learning associated with tools.

Impact of Pharmacotherapy on Cognitive Dysfunction in Patients with Multiple Sclerosis.

Cognitive impairment is a common symptom of multiple sclerosis (MS), adversely impacting many spheres of daily functioning. Yet the effectiveness of pharmacological interventions for cognitive impairment in MS is unclear. Clinicians and patients alike would benefit from formal guidelines regarding effective management of cognitive symptoms. We reviewed the background on the measurement, pathophysiology and risk factors for cognitive dysfunction in MS, and then examined the published clinical trials of pharmacotherapy, including both disease-modifying treatments (DMTs) and symptom-management therapies (SMTs). Our review of DMTs revealed only a single well-designed, randomized, controlled trial where intramuscular interferon (IFN)-ß1a, administered once weekly, was compared with placebo. The results showed significant benefits in terms of cognitive processing speed and memory. Less convincing but promising data have shown the potential benefits of IFN-ß1b and natalizumab. The literature on SMTs is replete with placebo-controlled, single-centre studies, with a failure to replicate initially promising results. The results for SMTs such as acetylcholinesterase inhibitors and psychostimulants are mixed. Some encouraging data show promise but not to a threshold of indication for standard clinical use. Numerous methodological factors hamper research in this area. Acknowledging the lack of firm conclusions, we argue that all DMTs are likely to benefit cognition and that, if otherwise safe, SMTs with some empirical support may be attempted at the discretion of the treating clinician. We offer some guidance on the assessment and monitoring of cognitive function to inform off-license treatment of cognitive impairment in MS patients.

Stable neuropsychiatric status in multiple sclerosis: a 3-year study.

Personality changes and neuropsychiatric symptoms are found in multiple sclerosis (MS), but no study has evaluated decline compared to healthy controls. This study assessed personality traits and neuropsychiatric symptoms over 3 years using the NEO Five Factor Inventory and the Neuropsychiatric Inventory. Additional metrics evaluated ambulation, manual dexterity and cognitive function. Contrary to hypothesis, patients showed no significant change in personality or neuropsychiatric status relative to controls. Patients were impaired in motor and cognitive function at baseline and follow-up, but showed only slowing in ambulation over time. The findings indicate that neuropsychiatric status is stable in MS over 3 years.

Interaction of memory systems during acquisition of tool knowledge and skills in Parkinson's disease.

Previous research suggests that different aspects of tool knowledge are mediated by different memory systems. It is believed that tool attributes (e.g., function, color) are represented as declarative memory while skill learning is supported by procedural memory. It has been proposed that other aspects (e.g., skilled tool use) may rely on an interaction of both declarative and procedural memory. However, the specific form of procedural memory underlying skilled tool use and the nature of interaction between declarative and procedural memory systems remain unclear. In the current study, individuals with Parkinson's disease (PD) and healthy controls were trained over 2 sessions, 3 weeks apart, to use a set of novel complex tools. They were also tested on their ability to recall tool attributes as well as their ability to demonstrate grasp and use of the tools to command. Results showed that, compared to controls, participants with PD showed intact motor skill acquisition and tool use to command within sessions, but failed to retain performance across sessions. In contrast, people with PD showed equivalent recall of tool attributes and tool grasping relative to controls, both within and across sessions. Current findings demonstrate that the frontal-striatal network, compromised in PD, mediates long-term retention of motor skills. Intact initial skill learning raises the possibility of compensation from declarative memory for frontal-striatal dysfunction. Lastly, skilled tool use appears to rely on both memory systems which may reflect a cooperative interaction between the two systems. Current findings regarding memory representations of tool knowledge and skill learning may have important implications for delivery of rehabilitation programs for individuals with PD.

Decreased functional magnetic resonance imaging activity in the hippocampus in favor of the caudate nucleus in older adults tested in a virtual navigation task.

The neuroimaging literature has shown consistent decreases in functional magnetic resonance imaging (fMRI) activity in the hippocampus of healthy older adults engaged in a navigation task. However, navigation in a virtual maze relies on spatial or response strategies known to depend on the hippocampus and caudate nucleus, respectively. Therefore, since the proportion of people using spatial strategies decreases with normal aging, we hypothesized that it was responsible for the observed decreases in fMRI activity in the hippocampus reported in the literature. The aim of this study was to examine the effects of aging on the hippocampus and caudate nucleus during navigation while taking into account individual navigational strategies. Young (N = 23) and older adults (N = 29) were tested using fMRI on the Concurrent Spatial Discrimination Learning Task, a radial task that dissociates between spatial and response strategies (in Stage 2) after participants reached criteria (in Stage 1). Success on Stage 2 requires that participants have encoded the spatial relationship between the target object and environmental landmarks, that is, the spatial strategy. While older adults required more trials, all participants reached criterion. fMRI results showed that, as a group, young adults had significant activity in the hippocampus as opposed to older adults who instead had significant activity in the caudate nucleus. Importantly, individual differences showed that the older participants who used a spatial strategy to solve the task had significant activity in the hippocampus. These findings suggest that the aging process involves a shift from using the hippocampus toward the caudate nucleus during navigation but that activity in the hippocampus is sustained in a subset of healthy older adults engaged in spatial strategies.

Dissociating the memory systems mediating complex tool knowledge and skills.

Previous research has suggested that different components of complex tool knowledge (e.g., attributes of a tool, how it is grasped, how it is used) may be mediated by different memory systems. For instance, while tool attributes may be represented in the declarative memory system, motor skill acquisition has been shown to be represented in the procedural memory system. Still other aspects of tool knowledge such as grasping for use and skilled tool use may rely on an integration of both declarative and procedural memory processes. However, the specific memory representations of different aspects of complex tool knowledge are still unclear. In the current study, D.A., an individual with amnesia, and a sample of matched controls were trained to use a set of novel complex tools. Subsequently, memory for different aspects of tool knowledge including motor skill acquisition, tool attributes, tool grasping, and skilled tool use was tested. Results showed that, in comparison to controls, D.A. was unimpaired in motor skill acquisition. In contrast, D.A. was severely impaired in recall of tool attributes, tool grasping, and skilled tool use, suggesting that these components of tool knowledge, at least in part, rely on declarative memory. Results also showed that providing contextual cues during tests of skilled tool use led to remarkable improvement in D.A.'s demonstration of tool use as well as his subsequent recall of tool functional knowledge. Implications of these findings and future directions are discussed.