Identification of Subtle Verbal Memory Deficits in Premanifest Huntington Disease Using the California Verbal Learning Test.

BACKGROUND: Verbal memory impairment in individuals with Huntington disease (HD) is well-documented; however, the nature and extent of verbal memory impairment in individuals with premanifest HD (pre-HD) are less understood. OBJECTIVE: To evaluate verbal memory function in individuals with pre-HD by comparing their performance on the California Verbal Learning Test to that of individuals with a clinical diagnosis of HD and that of a demographically similar group of adults with no family history of, or genetic risk for, HD, thereby reducing possible complications of psychiatric difficulties commonly experienced by individuals who are at risk for HD but are gene negative. METHODS: Participant groups included 77 adults with a diagnosis of HD, 23 premanifest gene carriers for HD (pre-HD), and 54 demographically similar, healthy adults. The California Verbal Learning Test-Second Edition (CVLT-II) was used to evaluate the participants' immediate and delayed recall, recognition, learning characteristics, errors, and memory retention. RESULTS: The pre-HD group performed significantly worse than the healthy group, yet significantly better than the HD group, on Short and Long Delay Recall (Free and Cued) and Recognition Discriminability. On Total Immediate Recall, Learning Slope, Semantic Clustering, and Intrusions, the pre-HD group performed similarly to the healthy group and significantly better than the HD group. None of the groups differed in their performance on Repetitions and a measure of retention. CONCLUSIONS: Subtle memory deficits can be observed during the premanifest stage of HD with use of a subset of indices from the CVLT-II.

Spatial memory ability during middle age may depend on level of spatial similarity.

Spatial memory impairment is well documented in old age; however, less is known about spatial memory during middle age. We examined the performance of healthy young, middle-aged, and older adults on a spatial memory task with varying levels of spatial similarity (distance). On low similarity trials, young adults significantly outperformed middle-aged adults, who significantly outperformed older adults (Ps < 0.05). On high similarity trials, young adults significantly outperformed middle-aged and older adults (Ps < 0.05); however, middle-aged and older adults did not differ. Subtle age-related changes in spatial memory may emerge during middle age, particularly when spatial similarity is high.

New Intrusion Analyses on the CVLT-3: Utility in Distinguishing the Memory Disorders of Alzheimer's versus Huntington's Disease.

OBJECTIVES: Research has shown that analyzing intrusion errors generated on verbal learning and memory measures is helpful for distinguishing between the memory disorders associated with Alzheimer's disease (AD) and other neurological disorders, including Huntington's disease (HD). Moreover, preliminary evidence suggests that certain clinical populations may be prone to exhibit different types of intrusion errors. METHODS: We examined the prevalence of two new California Verbal Learning Test-3 (CVLT-3) intrusion subtypes - across-trial novel intrusions and across/within trial repeated intrusions - in individuals with AD or HD. We hypothesized that the encoding/storage impairment associated with medial-temporal involvement in AD would result in a greater number of novel intrusions on the delayed recall trials of the CVLT-3, whereas the executive dysfunction associated with subcortical-frontal involvement in HD would result in a greater number of repeated intrusions across trials. RESULTS: The AD group generated significantly more across-trial novel intrusions than across/within trial repeated intrusions on the delayed cued-recall trials, whereas the HD group showed the opposite pattern on the delayed free-recall trials. CONCLUSIONS: These new intrusion subtypes, combined with traditional memory analyses (e.g., recall versus recognition performance), promise to enhance our ability to distinguish between the memory disorders associated with primarily medial-temporal versus subcortical-frontal involvement.

New Yes/No Recognition Memory Analysis on the California Verbal Learning Test-3: Clinical Utility in Alzheimer's and Huntington's Disease.

OBJECTIVES: The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington's disease [HD]). METHODS: We compared the performance of individuals with Alzheimer's disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. RESULTS: Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. CONCLUSIONS: Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833-841).

Who, when, and where? Age-related differences on a new memory test.

Our study examined age-related differences on a new memory test assessing memory for "who," "when," and "where," and associations among these elements. Participants were required to remember a sequence of pictures of different faces paired with different places. Older adults remembered significantly fewer correct face-place pairs in the correct sequence compared with young adults. Correlation analyses with standardized neuropsychological tests provide preliminary evidence for construct validity. Our results offer insight into age-related changes in the ability to remember associations between people and places at different points in time using a portable test that can be administered rapidly in various settings.

Spatial pattern separation differences in older adult carriers and non-carriers for the apolipoprotein E epsilon 4 allele.

We examined the performance of healthy young (n=57) and older adults (n=43) genotyped as apolipoprotein E-ε4 (APOE-ε4) carriers or APOE-ε4 non-carriers on a delayed match-to-sample task involving varying degrees of spatial interference hypothesized to assess spatial pattern separation. Older adult ε4 carriers were further divided into "impaired" and "unimpaired" groups based on their performance on a standardized test of verbal memory. We found that performance on the spatial pattern separation test increased as a function of decreased spatial interference across all groups. The older ε4 carriers in the impaired group performed significantly worse (p<.05) than unimpaired ε4 carriers, ε4 non-carriers, and young adults. The data suggest that spatial pattern separation may be less efficient in a subset of healthy older adults with subtle memory decline who are carriers of the ε4 allele. However, pattern separation performance may be comparable to that of young adults in a subset of older adult ε4 carriers and more broadly among non-carriers. Our findings offer additional evidence that pattern separation may vary in older adults, and they provide novel insight into pattern separation efficiency in ε4-positive older adults.

"Forgetting to remember" in Huntington's disease: a study of laboratory, semi-naturalistic, and self-perceptions of prospective memory.

Prospective memory (PM) is dependent on executive processes known to be impaired in Huntington's disease (HD); however, no study to the authors' knowledge has investigated PM in this group. We examined performance-based, semi-naturalistic, and self-reported PM in 20 individuals diagnosed with mild-moderate HD and 20 demographically similar controls. Relative to controls, HD participants demonstrated significantly lower scores in time-based PM, event-based PM (at a trend level), and the semi-naturalistic PM trial, all of which were marked by omission errors. HD participants demonstrated comparable recognition memory for the PM intentions relative to controls. HD and control participants also showed comparable scores in self-reported PM complaints. The results suggest that HD is associated with deficits in the strategic aspects of PM. HD-associated PM deficits also are evident in real-world situations, which may relate to an apparent meta-memory deficit for PM functioning as indicated by HD participants' overestimation of their PM performance on self-report.

Visual object pattern separation varies in older adults.

Young and nondemented older adults completed a visual object continuous recognition memory task in which some stimuli (lures) were similar but not identical to previously presented objects. The lures were hypothesized to result in increased interference and increased pattern separation demand. To examine variability in object pattern separation deficits, older adults were divided into impaired and unimpaired groups based on performance on a standardized serial list-learning task. Impaired older adults showed intact recognition memory, but were impaired relative to young and unimpaired older adults when identifying similar lure stimuli, demonstrating that object pattern separation varies in older adults.

Temporal sequence learning in healthy aging and amnestic mild cognitive impairment.

UNLABELLED: BACKGROUND/STUDY CONTEXT: Temporal sequence learning is a critical aspect of episodic memory that may be dependent on the temporal and frontal lobes. Because amnestic mild cognitive impairment (aMCI) and normal aging may result in changes within the temporal and frontal lobes, the present study investigated temporal sequence learning in patients with aMCI, cognitively normal older adults, and young adults. METHODS: On each trial of a temporal sequence task, circles appeared one at a time at the end of each arm of a computerized radial eight-arm maze. Participants were asked to reproduce the temporal sequence by placing numbered circles (1 to 8) on the arms of the eight-arm maze. Participants were presented with the same fixed sequence on each trial until the sequence was replicated without any errors, or until 15 trials were presented. RESULTS: Individuals with aMCI required significantly more trials to learn the temporal sequence compared with older adults (p < .05). Older adults required significantly more trials to learn the sequence than young adults (p < .05). Older adults and individuals with aMCI committed significantly more Trial 1 errors (p < .05) than young adults; however, there were no significant differences between the aMCI and older adult groups on Trial 1. CONCLUSION: The results suggest that temporal sequence learning deficits are detectable in aMCI. These deficits may disrupt a number of cognitive processes, such as episodic memory, that are important for the execution of daily activities. The results suggest that although temporal sequence learning declines with normal aging, this decline is greater in individuals who have a diagnosis of aMCI and are at higher risk for developing Alzheimer's disease.

Spatial pattern separation in cognitively normal young and older adults.

This study examined the ability of cognitively normal young adults (n = 30) and older adults (n = 30) to perform a delayed match-to-sample task involving varying degrees of spatial interference to assess spatial pattern separation. Each trial consisted of a sample phase followed by a choice phase. During the sample phase, a circle appeared briefly on a computer screen. The participant was instructed to remember the location of the circle on the screen. During the choice phase, two circles were displayed simultaneously, and the participant was asked to indicate which circle was in the same location as the sample phase circle. The two circles on choice phase trials were separated by one of four possible spatial separations: 0, 0.5, 1.0, and 1.5 cm. Smaller separations are likely to create increased overlap among memory representations, which may result in heightened interference and a greater need for pattern separation. Consistent with this hypothesis, performance increased as a function of increased spatial separation in both young and older adults. However, young adults outperformed older adults, suggesting that spatial pattern separation may be less efficient in older adults due to potential age-related changes in the dentate gyrus and CA3 hippocampal subregions. Older adults also were divided into older impaired and older unimpaired groups based on their performance on a standardized test of verbal memory. The older impaired group was significantly impaired relative to both the older unimpaired and young groups, suggesting that pattern separation deficits may be variable in older adults. The present findings may have important implications for designing behavioral interventions for older adults that structure daily living tasks to reduce interference, thus improving memory function.

Impact of Mild Cognitive Impairment on Quality of Life in Young and Typical Onset Parkinson's Disease.

INTRODUCTION: Younger age of onset and mild cognitive impairment (MCI) are both independently associated with poorer quality of life (QOL) in Parkinson's disease (PD). OBJECTIVES: The primary objective was to determine whether MCI differentially impacts QOL in young-onset PD (YOPD) and typical-onset PD (TOPD). METHODS: YOPD patients (n = 77) were diagnosed at age 50 or younger, TOPD (n = 77) were diagnosed after age 50, and the groups were matched for cognitive status, education, and disease duration. Patients' cognitive status was classified as MCI or cognitively normal (CN) based on MDS Level II criteria. QOL was assessed using the Parkinson's Disease Questionnaire (PDQ-39). ANCOVAs were conducted for each PDQ-39 subscale, with age of onset and cognitive status as between-subjects factors and several covariates included. RESULTS: An interaction for the Cognition domain revealed that in TOPD, PD-MCI patients reported poorer QOL than CN patients, whereas there was no effect of MCI on cognitive satisfaction in YOPD. There was a main effect of age on Emotional Well-Being, as YOPD reported poorer QOL than TOPD in this domain. There were main effects of cognitive status, with PD-MCI patients reporting worse QOL than CN patients in the domains of Social Support, Communication, ADLs, and Mobility. CONCLUSIONS: The interaction revealed that PD-MCI has a greater impact on degree of cognitive concerns ("cognitive QOL") in TOPD versus YOPD. A more nuanced understanding of the effects of age of onset, MCI, and their interactions on QOL in PD will inform interventions aimed at improving quality of life in this population.

Five-factor structure of the RBANS is supported in an Alzheimer's disease sample: Implications for validation of neuropsychological assessment instruments.

Development of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was theoretically driven, with the goal of providing an assessment of abilities across five cognitive domains. Since its development, numerous factor analytic studies have failed to provide empirical support for the proposed five-factor structure and, furthermore, have lacked consensus on the internal structure of this instrument. A key limitation of these prior studies is the use of normal or mixed clinical samples, a practice that can obscure distinctions that may be evident in specific homogeneous clinical samples. The current study examined the factor structure of the RBANS in a sample of 107 male Veterans diagnosed with probable Alzheimer's disease (AD). Confirmatory factor analysis of a model reflecting the five Index Scores (Immediate Memory, Visuospatial/Constructional, Language, Attention, and Delayed Memory) found that the proposed five-factor structure fit the data well. These findings suggest that the RBANS does measure five distinct constructs and use of Index Scores is appropriate. Furthermore, the current findings highlight the importance of testing construct validity of neuropsychological assessment instruments in specific homogeneous samples.

The emergence of age-related changes in recognition memory in healthy middle-aged adults using the CVLT-II.

Although age-related memory differences between young and older adults have been well documented, fewer studies have investigated memory changes in middle age. We examined the performance of healthy middle-aged adults (40-55 years of age; n = 32) in relation to healthy young (18-25 years of age; n = 57) and older adults (65+ years of age; n = 55) on variations of recognition discriminability (RD) indices derived from the California Verbal Learning Test-Second Edition (CVLT-II). Middle-aged adults performed significantly worse (ps < .05) than young adults on multiple RD indices that incorporate semantically related distractor items, suggesting memory changes in middle age may be associated with increased susceptibility to semantic interference. Moreover, middle-aged adults performed comparably to older adults across all RD indices, indicating the recognition profile of middle-aged adults on RD indices more closely resembles that of older adults than young adults.

Verbal episodic memory profiles in HIV-Associated Neurocognitive Disorders (HAND): A comparison with Huntington's disease and mesial temporal lobe epilepsy.

HIV-associated neurocognitive disorders (HAND) commonly feature verbal episodic memory impairment historically characterized by a retrieval deficit, consistent with a classic "subcortical" presentation; however, there are hints of a subtle shift toward a more "cortical" memory profile characterized by a primary encoding deficit. The current study evaluated this possibility by comparing the pattern of HAND-associated verbal episodic memory deficits to those of traditional "subcortical" (i.e., Huntington's disease; HD) versus "cortical" (i.e., left temporal lobe epilepsy with mesial temporal sclerosis; L-MTLE) profiles. Seventy-seven individuals with HAND, 47 individuals with HD, 21 individuals with L-MTLE, and 45 healthy participants were administered the California Verbal Learning Test - 2nd Edition (CVLT-II). CVLT-II profiles were classified as reflecting a primary encoding deficit, retrieval deficit, or a normal profile. Among participants with a deficit profile, the HAND group showed the highest rates of retrieval versus encoding profiles (71% vs. 29%), followed by HD (59% vs. 41%), L-MTLE (46% vs. 54%), and healthy (50% vs. 50%) groups. While significant profile heterogeneity was observed across clinical groups, findings suggest that HIV-associated verbal episodic memory impairments are most consistent with a traditional "subcortical," retrieval deficit profile, consistent with the primary frontostriatal neuropathogenesis of HIV disease.

Recall and Recognition Discriminability in Parkinson's Disease and Huntington's Disease.

BACKGROUND: Parkinson's disease (PD) and Huntington's disease (HD) are two neurodegenerative diseases affecting frontal-striatal function and memory ability. Studies using the original California Verbal Learning Test (CVLT) to examine recall and recognition abilities between these groups have produced mixed findings. Some found that individuals with HD demonstrate worse recall and recognition than those with PD, whereas others reported comparable performance. OBJECTIVE: We utilized multiple indices of recall and recognition discriminability, provided by the second and third editions of the CVLT (CVLT-II and CVLT-3, respectively), that allow for a more thorough assessment of more nuanced aspects of verbal memory function. METHODS: We examined differences between individuals with PD (n = 72) and those with HD (n = 77) on CVLT-II indices of recall discriminability (immediate, short delay free and cued, long delay free and cued) and recognition discriminability (total, source, semantic, and novel) using standardized scores while controlling for education and Dementia Rating Scale-2 scores. RESULTS: The HD group performed significantly worse than the PD group on all measures of recall and recognition discriminability (ps < 0.05), and group differences were associated with large Cohen's d effect sizes. CONCLUSIONS: Our findings suggest that individuals with HD are more impaired than individuals with PD in more nuanced aspects of recall and recognition memory function. These CVLT indices yield more thorough assessments of recall and recognition memory function and have the potential to improve efforts to characterize and distinguish profiles of memory loss in different neurodegenerative populations, including PD and HD.

Refining CVLT-II recognition discriminability indices to enhance the characterization of recognition memory changes in healthy aging.

The present study examined age-related differences on the four false-positive (FP) error subtypes found on the California Verbal Learning Test-Second Edition yes/no recognition memory trial and the influence of these subtypes on source and novel recognition discriminability (SoRD and NRD, respectively) index calculations. Healthy older (n = 55) adults generally made more FP errors than healthy young adults (n = 57). Accordingly, older adults performed worse than young adults on all SoRD and NRD indices. However, the manner in which FP error subtypes were incorporated into SoRD and NRD index calculations impacted the magnitudes of observed differences between and within the two age groups on SoRD and NRD indices. The present findings underline the importance of examining FP errors in assessments of recognition memory abilities, and using more refined indices of recognition discriminability to further elucidate the nature of age-related recognition memory impairment.

Impaired spatial pattern separation performance in temporal lobe epilepsy is associated with visuospatial memory deficits and hippocampal volume loss.

Individuals with chronic temporal lobe epilepsy (TLE) experience episodic memory deficits that may be progressive in nature. These memory decrements have been shown to increase with the extent of hippocampal damage, a hallmark feature of TLE. Pattern separation, a neural computational mechanism thought to play a role in episodic memory formation, has been shown to be negatively affected by aging and in individuals with known hippocampal dysfunction. Despite the link between poor pattern separation performance and episodic memory deficits, behavioral pattern separation has not been examined in patients with TLE. We examined pattern separation performance in a group of 22 patients with medically-refractory TLE and 20 healthy adults, using a task hypothesized to measure spatial pattern separation with graded levels of spatial interference. We found that individuals with TLE showed less efficient spatial pattern separation performance relative to healthy adults. Poorer spatial pattern separation performance in TLE was associated with poorer visuospatial memory, but only under high interference conditions. In addition, left hippocampal atrophy was associated with poor performance in the high interference condition in TLE. These data suggest that episodic memory impairments in patients with chronic, refractory TLE may be partially due to less efficient pattern separation, which likely reflects their underlying hippocampal dysfunction.

Everyday Functioning in Huntington's Disease: A Laboratory-Based Study of Financial Management Capacity.

One important limitation of prior studies examining functional decline in Huntington's disease (HD) has been the reliance on self-reported measures of ability. Since report-based methods can be biased by lack of insight, depression, and cognitive impairment, contrasting self-reported ability with measures that assess capacity may lead to a more comprehensive estimation of real-world functioning. The present study examined self-reported ability to perform instrumental activities of daily living (iADLs) and performance-based financial management capacity in 20 patients diagnosed with mild-moderate Huntington's disease (HD) and 20 demographically similar healthy adults. HD patients reported significantly greater declines in their ability to manage finances. On the capacity measure of financial management, HD patients performed significantly below healthy adults. Additionally, in the HD group there were no significant correlations between self-reported ability and capacity measures of financial management. HD patients endorsed declines in global iADL ability and exhibited deficits in functional capacity when performing a financial management task. Capacity measures may aid in assessing the extent to which HD patients accurately estimate real-world iADL performance, and the present findings suggest that such measures of capacity may be related to the cognitive, but not motor or affective, symptoms of HD.

Total recognition discriminability in Huntington's and Alzheimer's disease.

Both the original and second editions of the California Verbal Learning Test (CVLT) provide an index of total recognition discriminability (TRD) but respectively utilize nonparametric and parametric formulas to compute the index. However, the degree to which population differences in TRD may vary across applications of these nonparametric and parametric formulas has not been explored. We evaluated individuals with Huntington's disease (HD), individuals with Alzheimer's disease (AD), healthy middle-aged adults, and healthy older adults who were administered the CVLT-II. Yes/no recognition memory indices were generated, including raw nonparametric TRD scores (as used in CVLT-I) and raw and standardized parametric TRD scores (as used in CVLT-II), as well as false positive (FP) rates. Overall, the patient groups had significantly lower TRD scores than their comparison groups. The application of nonparametric and parametric formulas resulted in comparable effect sizes for all group comparisons on raw TRD scores. Relative to the HD group, the AD group showed comparable standardized parametric TRD scores (despite lower raw nonparametric and parametric TRD scores), whereas the previous CVLT literature has shown that standardized TRD scores are lower in AD than in HD. Possible explanations for the similarity in standardized parametric TRD scores in the HD and AD groups in the present study are discussed, with an emphasis on the importance of evaluating TRD scores in the context of other indices such as FP rates in an effort to fully capture recognition memory function using the CVLT-II.