Publications by authors named "Paul E Gilbert"

101 Publications

The Repeatable Battery for the Assessment of Neuropsychological Status, While Useful for Measuring Cognitive Changes in Manifest Huntington Disease, May Show Limited Utility in Premanifest Disease.

Cogn Behav Neurol 2022 Jul 14. Epub 2022 Jul 14.

Department of Psychology, San Diego State University, San Diego, California.

Background: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a brief, standardized neuropsychological test that assesses several areas of cognitive function. Recent studies, although sparse, have examined the use of the RBANS to detect cognitive deficits in individuals with manifest Huntington disease (HD); however, no studies have investigated its utility to detect cognitive deficits in individuals with premanifest HD (PreHD), where cognitive symptoms are thought to be more subtle.

Objective: To assess cognitive deficits in individuals with HD, particularly in individuals with PreHD, using an easily administered, brief but comprehensive, neuropsychological test.

Method: We administered the RBANS to 31 individuals with HD, 29 individuals with PreHD, and 22 healthy controls (HC) at an academic HD clinical research center and collected RBANS Total, Index, and subtest scores for group comparisons.

Results: The HD group had significantly lower RBANS Total, Index, and subtest scores than the HC. The PreHD group had significantly lower RBANS Total scores and Coding subtest scores than the HC, but no other significant group differences were identified.

Conclusion: Our results substantiate previous findings of significant impairment on the RBANS in individuals with HD. In addition, we are the first to demonstrate that, although the RBANS can identify deficits in psychomotor speed and information processing in individuals with PreHD, it does not appear to have the ability to detect impairment in any additional cognitive domains in individuals with PreHD.
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http://dx.doi.org/10.1097/WNN.0000000000000310DOI Listing
July 2022

Age-related differences in memory for "who," "when," and "where" are detectable in middle-aged adults.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2021 Apr 8:1-12. Epub 2021 Apr 8.

Department of Psychology, San Diego State University, San Diego, CA, USA.

Our study examined age-related differences across the adult lifespan using a recently developed test assessing memory for "who, when, and where" in addition to associations among these elements. Young (ages 18-25), middle-aged (ages 40-55), and older adults (ages 60+) were asked to remember a sequence of pictures of different faces paired with different places and place the pairs in the correct sequence. Young adults remembered significantly more face-place pairs in the correct sequence than middle-aged ( < .05) and older adults ( < .05), but there were no significant differences between middle-aged and older adults. Furthermore, young adults remembered significantly more face-place pairs irrespective of sequence than older adults ( < .05). However, there were no other significant differences among the groups.Using a rapidly administered test that integrates aspects of everyday episodic memory, we found evidence for age-related differences in test performance beginning in middle age.
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http://dx.doi.org/10.1080/13825585.2021.1908513DOI Listing
April 2021

Medication Management Performance in Parkinson's Disease: Examination of Process Errors.

Arch Clin Neuropsychol 2021 Oct;36(7):1307-1315

Research Service, Veterans Administration San Diego Healthcare System, San Diego, CA, 92161, USA.

Objective: Individuals with Parkinson's disease (PD) are at risk for increased medication mismanagement, which can lead to worse clinical outcomes. However, the nature of the errors (i.e., undertaking or overtaking medications) contributing to mismanagement and their relationship to cognition in PD is unknown. Therefore, this study sought to examine errors committed on the Medication Management Ability Assessment (MMAA) between PD participants with normal cognition (PD-NC) or mild cognitive impairment (PD-MCI) relative to healthy adults (HA).

Method: HA (n = 74), PD-NC (n = 102), and PD-MCI (n = 45) participants were administered the MMAA to assess undertaking, overtaking, and overall errors as well as overall performance (total score). Additionally, participants were administered a comprehensive neuropsychological battery from which cognitive composites of Attention, Learning, Memory, Language, Visuospatial, and Executive Functioning were derived.

Results: Separate negative binomial regression analyses indicated the PD-MCI group performed significantly worse overall on the MMAA (total score) and committed more undertaking and overall errors relative to HA and PD-NC. In the PD-MCI group, poorer MMAA performance was associated with worse delayed memory performance, whereas cognitive performance was not related to MMAA in HA or PC-NC.

Conclusion: Compared to PD and healthy adults with normal cognition, PD-MCI patients exhibited greater difficulty with medication management, particularly with undertaking medications. Poorer medication management in PD-MCI was associated with worse delayed recall. Thus, PD-MCI patients experiencing memory problems may require additional assistance with their medications. Findings have clinical relevance suggesting that objective measures of medication errors may assist clinicians in identifying PD patients needing adherence strategies.
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http://dx.doi.org/10.1093/arclin/acab004DOI Listing
October 2021

Central Cognitive Processing Speed Is an Early Marker of Huntington's Disease Onset.

Mov Disord Clin Pract 2021 Jan 28;8(1):100-105. Epub 2020 Dec 28.

Department of Psychology San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology San Diego California USA.

Background: Several studies have suggested that cognitive processing speed may be useful for assessing early cognitive change in premanifest Huntington's disease (HD); however, current measures lack the ability to control for the effects of motor dysfunction commonly found in HD. The Computerized Test of Information Processing (CTiP) is a rapidly administered computerized tool that allows for the examination of central cognitive processing speed by using motor-corrected scores to account for motor dysfunction.

Objective: To examine central cognitive processing speed as an early marker of HD onset using the CTiP.

Methods: The CTiP and other measures were administered to 102 HD gene carriers and 55 healthy adults (HA). Gene carriers included presymptomatic HD (pre-HD; n = 33), prodromal HD (pro-HD; ie, individuals close to disease onset; n = 23), and mild-moderate HD (HD; n = 46).

Results: The HD group performed significantly slower than all other groups (HA, pre-HD, and pro-HD) on most subtests (s < .05). Moreover, the pro-HD group performed significantly slower than the HA group on both motor-corrected subtests (s < 0.05). Effect sizes associated with significant group differences between the pro-HD and HA groups on motor-corrected CTiP subtests ( = 0.73 and 0.84) were similar to effect sizes associated with group differences on the Symbol Digit Modalities Test ( = .82) and other traditional cognitive assessments (Montreal Cognitive Assessment, = .75; Mini-Mental State Examination, = .84).

Conclusions: The CTiP may be a useful marker of deficits in central cognitive processing speed in individuals close to manifest onset of HD.
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http://dx.doi.org/10.1002/mdc3.13121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781078PMC
January 2021

Misattributions of the source of health-related information in HIV disease.

J Clin Exp Neuropsychol 2021 02 11;43(1):1-14. Epub 2020 Dec 11.

Department of Psychiatry, University of California, San Diego, CA, USA.

: Growing access to both legitimate and dubious sources of health information makes accurate source memory increasingly important, yet it may be negatively impacted by conditions that impair prefrontal functioning, including HIV. This study hypothesized that instructions supporting source encoding on a health-related memory task would disproportionately benefit source memory of people with HIV (PWH), and to examine the pattern of source memory errors that are observed.: 102 individuals (61 HIV+, 41 HIV-) completed comprehensive neurobehavioral (including health literacy) and neuromedical evaluations, and were randomly assigned to one of two conditions for a health-related memory task: explicitly participants to attend to the source of health statements presented to them, which were either health professionals or lay-persons, whereas no such instruction was provided in a condition.: There was no significant interaction of HIV status by condition or main effect of HIV (s>.05). There was a main effect of condition whereby those who received Attend to Source Instructions performed better on item-corrected source memory than those in the Control Instructions condition ( =.04). Those who received Control Instructions were more likely to misattribute the source of the health information to a health professional when the correct source was a lay-person (Cohen's = -0.53), which was correlated with poorer overall cognitive performance ( =.008) and performance-based measures of health literacy (s<.05).: Given that people are rarely reminded to attend to the source of new health information in the real world, the risk for misattributing health information to a qualified health professional in the absence of such instructions raises the concern that people may readily incorporate questionable health recommendations into their health regimen, particularly among persons with poorer cognitive functioning and lower levels of health literacy. This may have significant downstream health consequences such as drug interactions, side effects, and inefficacy.
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http://dx.doi.org/10.1080/13803395.2020.1851355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920983PMC
February 2021

APOE interacts with tau PET to influence memory independently of amyloid PET in older adults without dementia.

Alzheimers Dement 2021 01 4;17(1):61-69. Epub 2020 Sep 4.

San Diego State University/University of California, San Diego Joint Doctoral Program, San Diego.

Introduction: Apolipoprotein E (APOE) interacts with Alzheimer's disease pathology to promote disease progression. We investigated the moderating effect of APOE on independent associations of amyloid and tau positron emission tomography (PET) with cognition.

Methods: For 297 nondemented older adults from the Alzheimer's Disease Neuroimaging Initiative, regression equations modeled associations between cognition and (1) cortical amyloid beta (Aβ) PET levels adjusting for tau and (2) medial temporal lobe (MTL) tau PET levels adjusting for Aβ, including interactions with APOE ε4-carrier status.

Results: Adjusting for tau PET, Aβ was not associated with cognition and did not interact with APOE. In contrast, adjusting for Aβ PET, MTL tau was associated with all cognitive domains. Further, there was a stronger moderating effect of APOE on MTL tau and memory associations in ε4-carriers, even among Aβ-negative individuals.

Discussion: Findings suggest that APOE may interact with tau independently of Aβ and that elevated MTL tau confers negative cognitive consequences in Aβ-negative ε4 carriers.
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http://dx.doi.org/10.1002/alz.12173DOI Listing
January 2021

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

Cogn Behav Neurol 2020 03;33(1):16-22

San Diego State University-University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California.

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.
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http://dx.doi.org/10.1097/WNN.0000000000000219DOI Listing
March 2020

Is tau in the absence of amyloid on the Alzheimer's continuum?: A study of discordant PET positivity.

Brain Commun 2020 20;2(1):fcz046. Epub 2019 Dec 20.

VA San Diego Healthcare System, San Diego, CA 92161, USA.

The amyloid cascade model of Alzheimer's disease posits the primacy of amyloid beta deposition preceding tau-mediated neurofibrillary tangle formation. The amyloid-tau-neurodegeneration biomarker-only diagnostic framework similarly requires the presence of amyloid beta for a diagnosis on the Alzheimer's continuum. However, medial temporal lobe tau pathology in the absence of amyloid beta is frequently observed at autopsy in cognitively normal individuals, a phenomenon that may reflect a consequence of aging and has been labelled 'primary age-related tauopathy'. Alternatively, others argue that this tauopathy reflects an early stage of the developmental continuum leading to Alzheimer's disease. We used positron emission tomography imaging to investigate amyloid beta and tau positivity and associations with cognition to better inform the conceptualization of biomarker changes in Alzheimer's pathogenesis. Five hundred twenty-three individuals from the Alzheimer's Disease Neuroimaging Initiative who had undergone flortaucipir positron emission tomography imaging were selected to derive positron emission tomography positivity thresholds using conditional inference decision tree regression. A subsample of 301 individuals without dementia (i.e. those with normal cognition or mild cognitive impairment) had also undergone florbetapir positron emission tomography imaging within 12 months and were categorized into one of the four groups based on cortical amyloid and Braak stage I/II tau positivity: A-/T-, A+/T-, A-/T+, or A+/T+. Tau positivity in the absence of amyloid beta positivity (i.e. A-/T+) comprised the largest group, representing 45% of the sample. In contrast, only 6% of the sample was identified as A+/T-, and the remainder of the sample fell into A-/T- (22%) or A+/T+ (27%) categories. A-/T- and A+/T- groups had the best cognitive performances across memory, language and executive function; the A-/T+ group showed small-to-moderate relative decreases in cognition; and the A+/T+ group had the worst cognitive performances. Furthermore, there were negative associations between Braak stage I/II tau values and all cognitive domains only in the A-/T+ and A+/T+ groups, with strongest associations for the A+/T+ group. Among our sample of older adults across the Alzheimer's pathological spectrum, 7-fold fewer individuals have positron emission tomography evidence of amyloid beta pathology in the absence of tau pathology than the converse, challenging prevailing models of amyloid beta's primacy in Alzheimer's pathogenesis. Given that cognitive performance in the A-/T+ group was poorer than in individuals without either pathology, our results suggest that medial temporal lobe tau without cortical amyloid beta may reflect an early stage on the Alzheimer's pathological continuum.
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http://dx.doi.org/10.1093/braincomms/fcz046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001143PMC
December 2019

Interaction of APOE, cerebral blood flow, and cortical thickness in the entorhinal cortex predicts memory decline.

Brain Imaging Behav 2020 Apr;14(2):369-382

VA San Diego Healthcare System, 3350 La Jolla Village Dr., MC 151B, San Diego, CA, 9216, USA.

The ε4 allele of the apolipoprotein E (APOE) gene, a risk factor for cognitive decline, is associated with alterations in medial temporal lobe (MTL) structure and function, yet little research has been dedicated to understanding how these alterations might interact to negatively impact cognition. To bridge this gap, the present study employed linear regression models to determine the extent to which APOE genotype (ε4+, ε4-) modifies interactive effects of baseline arterial spin labeling MRI-measured cerebral blood flow (CBF) and FreeSurfer-derived cortical thickness/volume (CT/Vo) in two MTL regions of interest (entorhinal cortex, hippocampus) on memory change in 98 older adults who were cognitively normal at baseline. Baseline entorhinal CBF was positively associated with memory change, but only among ε4 carriers with lower entorhinal CT. Similarly, baseline entorhinal CT was positively associated with memory change, but only among ε4 carriers with lower entorhinal CBF. Findings suggest that APOE ε4 carriers may experience concomitant alterations in neurovascular function and morphology in the MTL that interact to negatively affect cognition prior to the onset of overt clinical symptoms. Results also suggest the presence of distinct multimodal neural signatures in the entorhinal cortex that may signal relative risk for cognitive decline among this group, perhaps reflecting different stages of cerebrovascular compensation (early effective vs. later ineffective).
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http://dx.doi.org/10.1007/s11682-019-00245-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165062PMC
April 2020

Cohort differences on the CVLT-II and CVLT3: Evidence of a negative Flynn effect on the attention/working memory and learning trials.

Clin Neuropsychol 2021 04 12;35(3):615-632. Epub 2019 Dec 12.

San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.

Objective: Although cohort effects on IQ measures have been investigated extensively, studies exploring cohort differences on verbal memory tests, and the extent to which they are influenced by socioenvironmental changes across decades (e.g. educational attainment; ethnic makeup), have been limited.

Method: We examined differences in performance between the normative samples of the CVLT-II from 1999 and the CVLT3 from 2016 to 2017 on the immediate- and delayed-recall trials, and we explored the degree to which verbal learning and memory skills might be influenced by the cohort year in which norms were collected versus demographic factors (e.g. education level).

Results: Multivariate analysis of variance tests and follow-up univariate tests yielded evidence for a cohort effect (also referred to as negative Flynn effect) on performance, controlling for demographic factors ( = .001). In particular, findings revealed evidence of a negative Flynn effect on the attention/working memory and learning trials (Trial 1, Trial 2, Trial 3, Trials 1-5 Total, List B; s < .007), with no significant cohort differences found on the delayed-recall trials. As expected, education level, age group, and ethnicity were significant predictors of CVLT performance (s < .01). Importantly, however, there were no interactions between cohort year of norms collection and education level, age group, or ethnicity on performance.

Conclusions: The clinical implications of the present findings for using word list learning and memory tests like the CVLT, and the potential role of socioenvironmental factors on the observed negative Flynn effect on the attention/working memory and learning trials, are discussed.
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http://dx.doi.org/10.1080/13854046.2019.1699605DOI Listing
April 2021

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

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2020 11 6;27(6):854-863. Epub 2019 Dec 6.

Department of Psychology, San Diego State University , San Diego, CA, USA.

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 (s < .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.
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http://dx.doi.org/10.1080/13825585.2019.1700897DOI Listing
November 2020

APOE modifies the interaction of entorhinal cerebral blood flow and cortical thickness on memory function in cognitively normal older adults.

Neuroimage 2019 11 4;202:116162. Epub 2019 Sep 4.

VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, 92161, USA; Department of Psychiatry, UC San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, 6363 Alvarado Court, Suite 103, San Diego, CA, 92120, USA. Electronic address:

Objective: The ε4 allele of the apolipoprotein E (APOE) gene increases risk for cognitive decline in normal and pathologic aging. However, precisely how APOE ε4 exerts its negative impact on cognition is poorly understood. The present study aimed to determine whether APOE genotype (ε4+ vs. ε4-) modifies the interaction of medial temporal lobe (MTL) resting cerebral blood flow (CBF) and brain structure (cortical thickness [CT], volume [Vo]) on verbal memory performance.

Methods: Multiple linear regression models were employed to investigate relationships between APOE genotype, arterial spin labeling MRI-measured CBF and FreeSurfer-based CT and Vo in four MTL regions of interest (left and right entorhinal cortex and hippocampus), and verbal memory performance among a sample of 117 cognitively normal older adults (41 ε4+, 76 ε4-) between the ages of 64 and 89 (mean age ​= ​73).

Results: Results indicated that APOE genotype modified the interaction of CBF and CT on memory in the left entorhinal cortex, such that the relationship between entorhinal CBF and memory was negative (lower CBF was associated with better memory) in non-carriers with higher entorhinal CT, positive (higher CBF was associated with better memory) in non-carriers with lower entorhinal CT, and negative (higher CBF was associated with worse memory) in ε4 carriers with lower entorhinal CT.

Conclusions: Findings suggest that older adult APOE ε4 carriers may experience vascular dysregulation and concomitant morphological alterations in the MTL that interact to negatively affect memory even in the absence overt clinical symptoms, providing potential insight into the mechanistic link between APOE ε4 and detriments in cognition. Moreover, findings suggest a distinct multimodal neural signature in ε4 carriers (higher CBF and lower CT in the entorhinal cortex) that could aid in the identification of candidates for future clinical trials aimed at preventing or slowing cognitive decline. Differential findings with respect to ε4 carriers and non-carriers are discussed in the context of neurovascular compensation.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819270PMC
November 2019

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

J Huntingtons Dis 2019 ;8(4):459-465

Department of Psychology, San Diego State University, San Diego, CA, USA.

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.
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http://dx.doi.org/10.3233/JHD-190346DOI Listing
July 2020

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

J Int Neuropsychol Soc 2019 09 7;25(8):878-883. Epub 2019 May 7.

San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California, USA.

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.
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http://dx.doi.org/10.1017/S1355617719000407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733627PMC
September 2019

Revisiting total recognition discriminability in Huntington's and Alzheimer's disease: New insights from the CVLT-3.

Appl Neuropsychol Adult 2021 Mar-Apr;28(2):132-139. Epub 2019 May 6.

San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California, USA.

The original and second editions of the California Verbal Learning Test (CVLT) used nonparametric and parametric methods, respectively, to assess Total Recognition Discriminability (RD). In a previous study, we found evidence that the nonparametric formula may be more sensitive than the parametric formula to high false positive (FP) rates and provide more accurate assessments of yes/no recognition in neurodegenerative populations prone to high FP rates, including Alzheimer's disease (AD). In the present study, we extended our investigation to examine the utility of CVLT-3 nonparametric and parametric Total RD indices in the assessment and comparison of yes/no recognition in individuals with Huntington's disease (HD) and AD in mild and moderate stages of dementia. Findings suggested that the CVLT-3 nonparametric Total RD index was more sensitive than the parametric index to HD and AD differences in yes/no recognition across mild and moderate stages of dementia. Additionally, group differences on total FP errors were more closely mirrored by group differences on the nonparametric Total RD index. The present results bolster our previous findings and highlight the utility of examining nonparametric (in addition to parametric) Total RD on the CVLT-3 in assessments of yes/no recognition involving clinical populations prone to high FP rates.
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http://dx.doi.org/10.1080/23279095.2019.1605993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832777PMC
October 2021

Collectivism Is Associated With Greater Neurocognitive Fluency in Older Adults.

Front Hum Neurosci 2019 11;13:122. Epub 2019 Apr 11.

Department of Psychology, San Diego State University, San Diego, CA, United States.

Neuropsychological research has been limited in the representation of cultural diversity due to various issues, raising questions regarding the applicability of findings to diverse populations. Nonetheless, culture-dependent differences in fundamental psychological processes have been demonstrated. One of the most basic of these, self-construal (individualism, collectivism), is central to how many other differences are interpreted. Self-construals may have possible consequences on social interactions, emotions, motivation, and cognition. This study aimed to evaluate the impact of self-construal on neurocognitive functions in older adults. A total of 86 community-dwelling older adults 60 years and older were assessed with three common self-report measures of self-construal along individualism and collectivism (IC). A cognitive battery was administered to assess verbal and non-verbal fluency abilities. Latent profile analysis (LPA) was used to categorize individuals according to IC, and one-way analyses of covariance (ANCOVA), including relevant covariates (e.g., ethnicity, gender, linguistic abilities), were used to compare neurocognitive functions between individualists and collectivists. Collectivists outperformed individualists on left frontally-mediated measures of verbal fluency (action, phonemic) after controlling for relevant covariates, = 6.942, = 0.010, = 0.061. Groups did not differ on semantic fluency, non-verbal fluency, or attention/working memory (all s > 0.05). These findings suggest a cognitive advantage in collectivists for verbal processing speed with an additional contribution of left frontal processes involved in lexicosemantic retrieval. Self-construal may provide a meaningful descriptor for diverse samples in neuropsychological research and may help explain other cross-cultural differences.
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http://dx.doi.org/10.3389/fnhum.2019.00122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470262PMC
April 2019

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

Learn Mem 2019 01 17;26(1):20-23. Epub 2018 Dec 17.

Department of Psychology, San Diego State University, San Diego, California 92182, USA.

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 (s < 0.05). On high similarity trials, young adults significantly outperformed middle-aged and older adults (s < 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.
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http://dx.doi.org/10.1101/lm.048280.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298540PMC
January 2019

Medication Management Capacity and Its Neurocognitive Correlates in Huntington's Disease.

Arch Clin Neuropsychol 2019 Oct;34(7):1121-1126

Department of Psychology, Washington State University, Pullman, WA, USA.

Objective: Although medication management is a necessary daily activity for individuals with Huntington's disease (HD), medication management abilities and their relation to cognitive functioning have not been evaluated.

Method: Twenty individuals with HD and 20 healthy adults (HA) completed the Medication Management Abilities Assessment (MMAA). Individuals with HD also completed a self-report medication management measure and neuropsychological tests assessing executive function, retrospective memory, and prospective memory.

Results: Individuals with HD performed significantly poorer and made more undertaking errors on the MMAA as compared to HA. No group differences were found in overtaking errors. In the HD group, significant associations were found between undertaking errors and perceived medication management ability as well as between MMAA task performance and measures assessing prospective memory and executive functions.

Conclusions: Medication management capacity was negatively affected in individuals with HD and may be associated with difficulty remembering to take medications in the future.
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http://dx.doi.org/10.1093/arclin/acy093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849462PMC
October 2019

Frequency and Correlates of Subjective Cognitive Impairment in HIV Disease.

AIDS Behav 2019 Mar;23(3):617-626

Department of Psychology, San Diego State University, San Diego, CA, USA.

The increasing prevalence of older adults living with HIV has raised growing concerns about a possible rise in the incidence of neurocognitive disorders due to HIV and other age-related factors. In typical aging, subjective cognitive impairment (SCI) among individuals with normal neurocognitive functioning may be an early manifestation of an incipient neurocognitive disorder. The current study examined the frequency and correlates of SCI in 188 HIV-infected adults without performance-based neurocognitive deficits or a current psychiatric disorder and 133 HIV seronegative comparison participants. All participants completed the Prospective and Retrospective Memory Questionnaire and Profile of Mood States Confusion/Bewilderment scale. Consistent with the diagnostic criteria proposed by Jessen et al. (Alzheimers Dement 10(6):844-852, 2014), participants were classified with SCI if their scores on either of the self-reported measures was greater than 1.5 SD above the normative mean. A logistic regression controlling for current mood complaints and lifetime history of substance use disorders revealed that HIV infection increased the odds of SCI (odds ratio= 4.5 [1.6, 15.4], p = 0.004). Among HIV+ individuals, SCI was associated with lower performance-based learning and delayed memory scores (Cohen's d range 0.41-0.42.) and poorer global everyday functioning (odds ratio= 8.5 [2.6, 15.9]), but not HIV disease severity (ps > 0.10). In a sample of individuals without neurocognitive impairment or elevated mood symptoms, HIV disease was associated with a nearly fivefold increased odds of SCI compared to seronegative individuals, which may indicate an increased risk for developing major neurocognitive disorders as these HIV+ individuals age.
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http://dx.doi.org/10.1007/s10461-018-2297-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481638PMC
March 2019

Computerised Dynamic Posturography in Premanifest and Manifest individuals with Huntington's Disease.

Sci Rep 2018 10 2;8(1):14615. Epub 2018 Oct 2.

Exercise Medicine Research Institute, Edith Cowan University, Perth, Australia.

Evidence from small-scale studies indicates that impairments in postural stability are an early and disabling feature of Huntington's disease (HD) and may be a useful clinical endpoint for disease modifying trials. Larger studies are needed to confirm these preliminary findings and the suitability of postural stability outcomes as clinical endpoints. Static and dynamic postural stability were evaluated in 54 premanifest HD, 36 manifest HD and 45 healthy individuals using the Sensory Organization Test (SOT) and Limits of Stability (LOS) test. Manifest HD displayed significantly lower scores on all SOT conditions and on the SOT composite score and had more falls than healthy and premanifest HD (p < 0.05). Premanifest and manifest HD demonstrated significantly lower endpoint excursion (p < 0.001), maximum excursion (p ≤ 0.001), and directional control (p ≤ 0.004) values than healthy individuals on the LOS test. Deficits in LOS were found to manifest on the left side of premanifest HD. Significant but low associations were observed between UHDRS-TMS, disease burden score, diagnostic confidence level, SOT conditions and SOT composite score. We confirm here that individuals with premanifest and manifest HD display significant impairments in static and dynamic postural stability. Dynamic posturography assessments should be considered as clinical endpoints for future disease modifying trials.
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http://dx.doi.org/10.1038/s41598-018-32924-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168504PMC
October 2018

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

J Int Neuropsychol Soc 2018 09 16;24(8):833-841. Epub 2018 Aug 16.

1San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology,San Diego/La Jolla,California.

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).
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http://dx.doi.org/10.1017/S1355617718000474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170690PMC
September 2018

Rates of Neuropsychological Dysfunction in Fibromyalgia and Rheumatoid Arthritis: An Automated Clinical Rating Approach.

J Clin Rheumatol 2019 Sep;25(6):252-257

Department of Psychiatry, University of California, San Diego, CA.

Background/objective: Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology that can include subjective cognitive symptoms and variable evidence of cognitive dysfunction. Rates of occurrence and severity of cognitive impairment remain unclear. Additionally, comparison of this group with other pain conditions has been limited. The current cross-sectional study sought to identify rates of clinically significant cognitive impairment in FM and rheumatoid arthritis (RA) using an automated clinical rating approach.

Methods: A total of 61 females (32 with FM, 29 with RA) completed a comprehensive neuropsychological (NP) battery and an assessment of personality and psychological distress. All study measures were completed in one visit and all participants were recruited over the span of 3 years. Demographically corrected NP scores were used to compare participants with normative expectations and a summary score was calculated to compare groups on NP impairment.

Results: Compared to normative expectations using a 1 standard deviation cutoff, moderately increased rates of cognitive deficits were observed in both groups (FM = 23.3%, RA = 34.5%), with most test scores in affected individuals falling in the mild to moderate ranges of impairment. Compared to RA, FM participants endorsed higher and significant levels of psychological symptoms overall. These were not associated with cognitive performance in either patient group.

Conclusions: Increased rates of cognitive dysfunction as well as psychological distress exist in both FM and RA compared to a normative sample. However, psychological distress was unrelated to cognition in both groups. These findings have implications regarding the clinical presentation of individuals with FM and RA.
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http://dx.doi.org/10.1097/RHU.0000000000000837DOI Listing
September 2019

Differential Effect of APOE ɛ4 Status and Elevated Pulse Pressure on Functional Decline in Cognitively Normal Older Adults.

J Alzheimers Dis 2018 ;62(4):1567-1578

Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

Background/objective: The APOE ɛ4 allele and increased vascular risk have both been independently linked to cognitive impairment and dementia. Since few studies have characterized how these risk factors affect everyday functioning, we investigated the relationship between APOE ɛ4 genotype and elevated pulse pressure (PP) on functional change in cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Methods: 738 normally aging participants underwent APOE genotyping, and baseline PP was calculated from blood pressure indices. The Functional Activities Questionnaire (FAQ) was completed by participants' informant at baseline and 6, 12, 24, 36, and 48-month follow-up visits. Multiple linear regression and multilevel modeling were used to examine the effects of PP and APOE ɛ4 genotype on cross-sectional and longitudinal FAQ scores, respectively.

Results: Adjusting for demographic and clinical covariates, results showed that both APOE ɛ4 status and elevated PP predicted greater functional difficulty trajectories across four years of follow-up. Interestingly, however, elevated PP was associated with greater functional decline over time in ɛ4 non-carriers versus carriers.

Conclusion: Results show that, although APOE ɛ4 status is the prominent predictor of functional difficulty for ɛ4 carriers, an effect of arterial stiffening on functional difficulty was observed in non-carriers. Future studies are needed in order to clarify the etiology of the association between PP and different brain aging processes, and further explore its utility as a marker of dementia risk. The present study underscores the importance of targeting modifiable risk factors such as elevated PP to prevent or slow functional decline and pathological brain aging.
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http://dx.doi.org/10.3233/JAD-170918DOI Listing
May 2019

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

Neuropsychologia 2018 03 8;111:209-215. Epub 2018 Feb 8.

Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, CA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neuropsychologia.2018.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873595PMC
March 2018

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

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2018 09 31;25(5):767-782. Epub 2017 Aug 31.

a Joint Doctoral Program in Clinical Psychology , San Diego State University/University of California San Diego , San Diego/La Jolla , CA , USA.

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.
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http://dx.doi.org/10.1080/13825585.2017.1372358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832615PMC
September 2018

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

Appl Neuropsychol Adult 2019 Jan-Feb;26(1):17-27. Epub 2017 Aug 29.

a Department of Psychiatry , University of California San Diego , La Jolla , California.

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 - 2 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.
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http://dx.doi.org/10.1080/23279095.2017.1353993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832571PMC
April 2019

Effects of Age and Gender on Recall and Recognition Discriminability.

Arch Clin Neuropsychol 2017 Dec;32(8):972-979

San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, 92120, USA.

Objective: Recall and recognition memory abilities are known to decline with increasing age, yet much of the evidence stems from studies that used simple measures of total target recall or recognition. The California Verbal Learning Test-Second Edition (CVLT-II) includes a new measure of recall discriminability that is analogous to recognition discriminability. These discriminability measures yield more thorough assessments of recall and recognition by accounting for intrusion and false positive errors, respectively. Research also has shown that women outperform men on verbal episodic memory tests. However, gender differences in recall and recognition discriminability and the age-by-gender interaction on these constructs have not been thoroughly examined.

Method: Cognitively healthy adults (N = 223) 18-91 years in age completed the CVLT-II. Multiple regression analyses were conducted to examine effects of age, gender, and the age-by-gender interaction on CVLT-II subtypes of recall and recognition discriminability.

Results: Discriminability scores decreased with increasing age, and women outperformed men. There was an age-by-gender interaction on total, immediate, and free recall discriminability - the negative association between age and scores was stronger in men than in women. Exploratory analyses revealed an inverted U-shaped relationship between age and recall discriminability scores in women.

Conclusions: The present findings support and expand upon the extant literature on aging, gender, and verbal episodic memory, plus describe a novel age-by-gender interaction intrinsic to subtypes of recall discriminability. The findings suggest that methods traditionally used to assess recognition memory function can be used to elucidate age- and gender-related changes in recall ability across the adult lifespan.
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http://dx.doi.org/10.1093/arclin/acx024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860276PMC
December 2017

Age-related differences on a new test of temporal order memory for everyday events.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2018 05 7;25(3):319-332. Epub 2017 Mar 7.

a Department of Psychology , San Diego State University , San Diego , CA , USA.

We developed a new test to examine incidental temporal order memory for a self-generated sequence of tasks one might complete in everyday life. Young and older adults were given 10 cards, each listing a task one might accomplish in a typical day. Participants were asked to self-generate a "to do" list by placing the 10 cards in a sequence representing the order in which they would accomplish the tasks, but were not informed of a subsequent memory test. We assessed immediate free recall, delayed free recall, and delayed cued recall for the order of the tasks in the sequence. Older adults were significantly impaired relative to young adults on immediate free recall, delayed free recall, and delayed cued recall. Correlation analyses with standardized neuropsychological tests provide preliminary evidence for construct validity for our test, which is portable and can be rapidly administered in clinical or laboratory settings.
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http://dx.doi.org/10.1080/13825585.2017.1298716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935107PMC
May 2018

Evaluating Recall and Recognition Memory Using the Montreal Cognitive Assessment: Applicability for Alzheimer's and Huntington's Diseases.

Am J Alzheimers Dis Other Demen 2016 12 26;31(8):658-663. Epub 2016 Sep 26.

Department of Neurosciences, University of California, San Diego, CA, USA.

We sought to investigate whether the Montreal Cognitive Assessment (MoCA) could provide a brief assessment of recall and recognition using Huntington disease (HD) and Alzheimer disease (AD) as disorders characterized by different memory deficits. This study included 80 participants with HD, 64 participants with AD, and 183 community-dwelling control participants. Random-effects hierarchical logistic regressions were performed to assess the relative performance of the normal control (NC), participants with HD, and participants with AD on verbal free recall, cued recall, and multiple-choice recognition on the MoCA. The NC participants performed significantly better than participants with AD at all the 3 levels of assessment. No difference existed between participants with HD and NC for cued recall, but NC participants performed significantly better than participants with HD on free recall and recognition. The participants with HD performed significantly better than participants with AD at all the 3 levels of assessment. The MoCA appears to be a valuable, brief cognitive assessment capable of identifying specific memory deficits consistent with known differences in memory profiles.
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http://dx.doi.org/10.1177/1533317516668573DOI Listing
December 2016
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