Utility of the ALSFRS-R for predicting ALS and comorbid disease neuropathology: The Veterans Affairs Biorepository Brain Bank.

INTRODUCTION/AIMS: The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) is commonly used to track ALS disease progression; however, there are gaps in the literature regarding the extent to which the ALSFRS-R relates to underlying central nervous system (CNS) pathology. The current study explored the association between ALSFRS-R (total and subdomain) scores and postmortem neuropathology (both ALS-specific and comorbid disease). METHODS: Within our sample of 93 military veterans with autopsy-confirmed ALS, we utilized hierarchical cluster analysis (HCA) to identify discrete profiles of motor dysfunction based on ALSFRS-R subdomain scores. We examined whether emergent clusters were associated with neuropathology. Separate analyses of variance and covariance with post-hoc comparisons were performed to examine relevant cluster differences. RESULTS: Analyses revealed significant correlations between ALSFRS-R total and subdomain scores with some, but not all, neuropathological variables. The HCA illustrated three groups: Cluster 1-predominantly diffuse functional impairment; Cluster 2-spared respiratory/bulbar and impaired motor function; and Cluster 3-spared bulbar and impaired respiratory, and fine and gross motor function. Individuals in Cluster 1 (and to a lesser degree, Cluster 3) exhibited greater accumulation of ALS-specific neuropathology and less comorbid neuropathology than those in Cluster 2. DISCUSSION: These results suggest that discrete patterns of motor dysfunction based on ALSFRS-R subdomain scores are related to postmortem neuropathology. Findings support use of ALSFRS-R subdomain scores to capture the heterogeneity of clinical presentation and disease progression in ALS, and may assist researchers in identifying endophenotypes for separate assessment in clinical trials.

Optimizing Subjective Cognitive Decline to Detect Early Cognitive Dysfunction.

BACKGROUND: The utility of subjective cognitive decline (SCD) as an indicator of preclinical AD is overshadowed by its inconsistent association with objective cognition. OBJECTIVE: This study examines if manipulations of SCD measurement affect its association with early cognitive dysfunction characteristic of preclinical AD. METHODS: Cognitively healthy older adults (n = 110) completed SCD questionnaires that elicited complaints in general, compared to 5 years ago (retrospective SCD) and compared to their peers (age-anchored SCD) in binary and Likert scales. Outcome cognitive tasks included an associative memory task (Face-Name Test), a visual short-term memory binding task (STMB test), and a clinical neuropsychological list learning test (Selective Reminder Test). RESULTS: SCD complaints, when compared to age-matched peers (age-anchored SCD) were endorsed less frequently than complaints compared to 5 years ago (retrospective SCD) (p < 0.01). In demographically adjusted regressions, age-anchored ordinal-rated SCD was associated with short term memory binding (ß= -0.22, p = 0.040, CI = -0.45, -0.01), associative memory (ß= -0.26, p = 0.018, CI = -0.45, -0.06), and list learning (ß= -0.31, p = 0.002, CI = -0.51, -0.12). Retrospective and general ordinal-rated SCD was associated with associative memory (ß= -0.25, p = 0.012, CI = -0.44, -0.06; ß= -0.29, p = 0.003, CI = -0.47, -0.10) and list learning only (ß= -0.25, p = 0.014, CI = -0.45, -0.05; ß= -0.28, p = 0.004, CI = -0.48, -0.09). CONCLUSION: Ordinal age-anchored SCD appears better suited than other SCD measurements to detect early cognitive dysfunction characteristic of preclinical AD.

Translational Aspects of the Multidisciplinary Study of Metacognition.

Metacognition, self-awareness, self-knowledge, and insight each refer to the process by which individuals reflect upon and appraise their own abilities. Self-awareness is a complex, dynamic, and multifactorial construct that spans various domains such as motor, sensory, functional and cognitive abilities. Various disciplines including cognitive psychology, neuropsychology, psychiatry and neurology have attempted to understand healthy and pathologic self-awareness of cognition in particular. Although intrinsically connected, the study of healthy and pathologic states of self-awareness have remained relatively discrete from one another. Indeed, different disciplines examining self-awareness of cognition have operationalized and measured awareness through distinct theoretical frameworks. More recently, however, various authors have attempted to bridge constructs across disciplines in an effort to develop a unitary theoretical model for self-awareness of cognitive abilities. In this commentary, we summarize the study of self-awareness of cognitive abilities across various disciplines, highlighting translational aspects between them.

Cross domain self-monitoring in anosognosia for memory loss in Alzheimer's disease.

Anosognosia for memory loss is a common feature of Alzheimer's disease (AD). Recent theories have proposed that anosognosia, a disruption in awareness at a global level, may reflect specific deficits in self-monitoring, or local awareness. Though anosognosia for memory loss has been shown to relate to memory self-monitoring, it is not clear if it relates to self-monitoring deficits in other domains (i.e., motor). The current study examined this question by analyzing the relationship between anosognosia for memory loss, memory monitoring, and motor monitoring in 35 individuals with mild to moderate AD. Anosognosia was assessed via clinical interview before participants completed a metamemory task to measure memory monitoring, and a computerized agency task to measure motor monitoring. Cognitive and psychological measures included memory, executive functions, and mood. Memory monitoring was associated with motor monitoring; however, anosognosia was associated only with memory monitoring, and not motor monitoring. Cognition and mood related differently to each measure of self-awareness. Results are interpreted within a hierarchical model of awareness in which local self-monitoring processes are associated across domain, but appear to only contribute to a global level awareness in a domain-specific fashion.

Mood and Personality Characteristics are Associated with Metamemory Knowledge Accuracy in a Community-Based Cohort of Older Adults.

OBJECTIVES: Emerging work reveals the neuroanatomic changes that compromise metacognition; however, little is known about the impact of premorbid factors. Research suggests that psychological variables influence the perception of cognition, but whether they influence the accuracy of those perceptions (i.e., metacognition) has not been directly examined. PARTICIPANTS AND METHODS: Using Latent Class Analysis (LCA), we tested for discrete personality (NEOFFI) and mood (STAI, BDI-II, and GDS) classes among a community-based cohort of 151 older adults, enrolled in the NKI-Rockland study. Metamemory was calculated by comparing subjective memory ratings (modified Cognitive Failures Questionnaire) to objective memory (Rey Auditory Verbal Learning Test) to determine the degree to which individuals were overconfident, underconfident, or accurate in their self-assessment. A generalized linear model was used to examine whether metamemory differed across the emergent classes. A one sample t test was used to determine whether the metamemory scores of the emergent classes were statistically significantly different from zero, that is, over or under confident. RESULTS: Two discrete classes emerged in the LCA: Class 1 was characterized predominantly by high extraversion and conscientiousness and low neuroticism and anxiety; Class 2 was characterized predominantly by low extraversion and conscientiousness and high neuroticism and anxiety. Metamemory differed significantly as a function of Class Membership (F(4,151)=5.42; p<.001), with Class 1 demonstrating accurate metamemory (M=0.21; SD=1.31) and Class 2 demonstrating under-confidence (M=-0.59; SD=1.39) in their memory. CONCLUSIONS: The significant association between psychological factors and metamemory knowledge accuracy suggests that such characteristics may be important to consider in the conceptualization, assessment, and treatment of metacognitive disturbances. (JINS, 2018, 24, 498-510).