Memory Difficulties Research Articles

Using recognition testing to support semantic learning in developmental amnesia

ABSTRACT Patients with developmental amnesia (DA) have suffered hippocampal damage in infancy and subsequently shown poor episodic memory, but good semantic memory. It is not clear how patients with DA learn semantic information in the presence of episodic amnesia. However, patients with DA show good recognition memory and it is possible that semantic learning may be supported by recognition. Building on previous work, we compared two methods for supporting semantic learning in DA; recognition-learning and recall-learning. In each condition, a patient with DA (aged 8 years) was presented with semantic information in animated videos. After each presentation of a video, learning was supported by an immediate memory test. Two videos were paired with a cued recall test. Another two videos were paired with a multiple-choice test to enable recognition-based learning. The outcome measure was semantic recall performance after a short delay of 30 min and a long delay of one week. Results showed a benefit of recognition-learning compared to recall-learning on cued recall in the patient with DA (76% vs. 35%). This finding indicates that young people with severe hippocampal damage can utilize recognition to support semantic learning. This has implications for the support of school-aged children with episodic memory difficulties.

Memory performance on the ChAMP in autism spectrum disorder with and without attention-deficit/hyperactivity disorder

Memory difficulties have been identified in youth with neurodevelopmental conditions including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The Child and Adolescent Memory Profile (ChAMP) is a newer memory measure with a burgeoning research base. This study seeks to explore memory performance on the Lists and Objects subtests of the ChAMP in a clinical sample of those with ASD with/without co-occurring ADHD. Participants were 146 youth referred for a neuropsychological evaluation (M age = 11.8 years; 76.03% male) diagnosed with ASD (N = 92 with ADHD, N = 54 without). Logistic regression (p = .393) indicated ChAMP performance is not predictive of whether the ASD group had co-occurring ADHD indicating there is no additive effect on memory. Compared to the ChAMP examiner’s manual ASD sample, this study sample performed significantly better (p <.001) on all ChAMP measures. While the ChAMP is sensitive to memory difficulties in neurodevelopmental disorders, as indicated by the performance of the manual sample, the ASD sample of the manual may differ from other ASD samples. There were no differences between verbal and visual memory performance across the present study’s sample.

Verbal memory impairments in mood disorders and psychotic disorders: A systematic review of comparative studies

BackgroundMood and psychotic disorders are both associated with verbal memory impairments. Verbal memory represents an important treatment target for both disorders. However, whether the neurocognitive and neurophysiological profiles of verbal memory impairments differ between specific disorders within these two diagnostic categories and healthy controls remains unclear. The current systematic review synthesized findings from comparative studies which used behavioural and neuroimaging tasks to investigate verbal memory impairments between: (1) mood disorder, psychotic disorder, and healthy control groups; and (2) mood disorder without psychotic features, mood disorder with psychotic features, and healthy control groups. MethodsThe search strategy combined terms related to three main concepts: ‘mood disorders’, ‘psychotic disorders’, and ‘verbal memory’. Searches were executed in Embase, MEDLINE, PsycInfo, and PubMed databases. A total of 38 articles met the full eligibility criteria and were included in the final narrative synthesis. Findings were stratified by memory domain (overall composite score, verbal working memory, immediate recall, delayed recall, and recognition memory) and by illness phase (acute and non-acute). ResultsMood and psychotic disorders displayed consistent verbal memory impairments compared to healthy controls during the acute and non-acute phases. Few significant differences were identified in the literature between mood and psychotic disorders, and between mood disorders with and without psychotic features. Individuals with schizophrenia were found to have decreased immediate and delayed verbal recall performance compared to bipolar disorder groups during the acute phase. Major depressive disorder groups with psychotic features were also found to have decreased delayed verbal recall performance compared to those without psychosis during the acute phase. No consistent differences were identified between mood and psychotic disorders during the non-acute phase. Finally, preliminary evidence suggests there may be functional abnormalities in important frontal and temporal brain regions related to verbal memory difficulties in both mood and psychotic disorders. DiscussionThe current findings have potential implications for the diagnosis and treatment of cognitive impairments in mood and psychotic disorders. Verbal recall memory may serve as a sensitive tool in the risk stratification of cognitive impairments for certain mood and psychotic disorders. Moreover, since no widespread differences between clinical groups were identified, the evidence supports providing targeted interventions for verbal memory, such as pharmacological and non-pharmacological interventions, through a trans-diagnostic approach in mood and psychotic disorders.

The relationship between cognitive and affective control and adolescent mental health.

Cognitive control problems have been implicated in the etiology and maintenance of mental health problems, including depression, in adults. Studies in adolescents have been more equivocal, with some showing changes in cognitive control in adolescents with mental health problems, whereas others fail to show an association. This study examines whether adolescent mental health is associated with affective control, the application of cognitive control in affective contexts, which shows more protracted development than cognitive control. The present study investigated the association of cognitive and affective control with depressive symptomatology and self-reported diagnostic history of mental health problems in adolescents. The study included 1929 participants (M age=13.89) from the Future Proofing Study (N=6,388, 11-16years), who completed affective (incl., affective stimuli) and/or cognitive (incl., neutral stimuli) versions of a working memory (backward digit-span) and/or shifting (card-sorting) task at least once within 3weeks of assessing mental health. Poorer working memory was associated with greater depressive symptomatology in adolescents (β=-0.06, p=.004), similarly across cognitive and affective control conditions (β=-0.02, p=.269). Adolescents with self-reported diagnostic history of mental health problems had significantly poorer shifting ability in affective compared to cognitive control conditions (b=0.05, p=.010), whereas for adolescents with no self-reported diagnoses, shifting ability did not differ between conditions (b=-0.00, p=.649). The present analyses suggest that working memory difficulties, in particular, may be associated with the experience of current depressed mood in adolescents. Problems with affective shifting may be implicated in a range of mental health problems in adolescents. Given the ubiquitous need for efficient cognitive functioning in daily life, enhancing cognitive and affective control in adolescents may be a promising means of improving functioning across a range of domains, including affective functioning, and by extension, adolescent mental health.

Experiences of age-related declining navigation abilities and impact on use of outdoor environments: a qualitative study of young-old adults with self-reported memory difficulties

Abstract Laboratory-based experiments show ageing negatively impacts navigation abilities, yet a paucity of research explores lived experience. This exploratory study examined young-old adults' experiences of declining navigation abilities during 16 semi-structured telephone interviews. Findings reveal: (a) ‘Behavioural drivers’ that underpinned the participants' experiences and actions when engaging with their environments, (b) ‘Avoidance’ and (c) ‘Active’ strategies that were adopted by the participants. Declining cognitive function appeared to have a negative impact on participants' perceived abilities and confidence to navigate unfamiliar outdoor environments, which in turn influenced the strategies they chose to adopt. Future psychosocial interventions should draw on neuropsychological theory to ensure retention of navigation skills and confidence for as long as possible.

A Rare Case of Metastatic Rectal Cancer to the Brain Presenting with Headaches and Memory Difficulties.

A Rare Case of Metastatic Rectal Cancer to the Brain Presenting with Headaches and Memory Difficulties.

Self-reported memory of autistic young adults and associated real-world outcomes

PurposeAlthough autistic adults have demonstrated weaker memory performance on lab-based measures in comparison to neurotypical peers, research on self-reported memory abilities in this group is scarce. Shedding light on memory abilities of autistic adults is important, as memory difficulties may impact daily living outcomes, an area of difficulty for autistic individuals. Thus, the current study aimed to characterize the self-reported memory complaints of a large sample of autistic adults in comparison to neurotypical adults. MethodsThis study included data from 396 autistic young adults and 396 neurotypical young adults between the ages of 18 and 39 years and with similar background characteristics. Autistic adults were recruited from the Simons Powering Autism Research (SPARK) participant registry, and data from neurotypical adults were obtained from a large-scale internet study. The responses to the Prospective and Retrospective Memory Questionnaire were compared by diagnostic group, and within the autistic group, relations between memory complaints and real-world outcomes (activities of daily living [ADLs] and postsecondary employment and educational activities) were examined. ResultsThe results indicated that young autistic adults reported greater memory problems than their neurotypical peers, regardless of memory type, and autistic adults reported a comparable pattern of complaints to their neurotypical peers (i.e., greater prospective memory complaints in comparison to retrospective memory complaints). Additionally, we found a negative association between memory complaints and outcomes (i.e., greater memory complaints were associated with less independence in ADLs and less favorable postsecondary outcomes). ConclusionThe significant association between subjective memory complaints and real-world outcomes suggests that memory abilities are an important contributor to daily living skills and post-secondary outcomes among autistic adults and could represent a target for future intervention development.

1 Associations of Locus of Control and Memory Self-Awareness in Older Adults with and without MCI

Objective:While loss of insight into one’s cognitive impairment (anosognosia) is a feature in Alzheimer’s disease dementia, less is known about memory self-awareness in cognitively unimpaired (CU) older adults or mild cognitive impairment (MCI) or factors that may impact self-awareness. Locus of control, specifically external locus of control, has been linked to worse cognitive/health outcomes, though little work has examined locus of control as it relates to self-awareness of memory functioning or across cognitive impairment status. Therefore, we examined associations between locus of control and memory self-awareness and whether MCI status impacted these associations.Participants and Methods:Participants from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (mean age=73.51; 76% women; 26% Black/African American) were classified as CU (n=2177) or MCI (amnestic n=313; non-amnestic n=170) using Neuropsychological Criteria. A memory composite score measured objective memory performance and the Memory Functioning Questionnaire measured subjective memory. Memory self-awareness was defined as objective memory minus subjective memory, with positive values indicating overreporting of memory difficulties relative to actual performance (hypernosognosia) and negative values indicating underreporting (hyponosognosia). Internal (i.e., personal skills/attributes dictate life events) and external (i.e., environment/others dictate life events) locus of control scores came from the Personality in Intellectual Aging Contexts Inventory. General linear models, adjusting for age, education, sex/gender, depressive symptoms, general health, and vocabulary examined the effects of internal and external locus of control on memory self-awareness and whether MCI status moderated these associations.Results:Amnestic and non-amnestic MCI participants reported lower internal and higher external locus of control than CU participants. There was a main effect of MCI status on memory self-awareness such that amnestic MCI participants showed the greatest degree of hyponosognosia/underreporting, followed by non-amnestic MCI, and CU participants slightly overreported their memory difficulties. While, on average, participants were fairly accurate at reporting their degree of memory difficulty, internal locus of control was negatively associated with self-awareness such that higher internal locus of control was associated with greater underreporting (ß=-.127, 95% CI [-.164, -.089], p&lt;.001). MCI status did not moderate this association. External locus of control was positively associated with self-awareness such that higher external locus of control was associated with greater hypernosonosia/overreporting (ß=.259, 95% CI [.218, .300], p&lt;.001). Relative to CU, amnestic, but not non-amnestic, MCI showed a stronger association between external locus of control and memory self-awareness. Specifically, higher external locus of control was associated with less underreporting of cognitive difficulties in amnestic MCI (ß=.107, 95% CI [.006, .208], p=.038).Conclusions:In CU participants, higher external locus of control was associated with greater hypernosognosia/overreporting. In amnestic MCI, the lower external locus of control associations with greater underreporting of objective cognitive difficulties suggests that perhaps reduced insight in some people with MCI may result in not realizing the need for external supports, and therefore not asking for help from others. Alternatively, in amnestic participants with greater external locus of control, perhaps the environmental cues/feedback translate to greater accuracy in their memory self-perceptions. Longitudinal analyses are needed to determine how memory self-awareness is related to future cognitive declines.

13 Verbal Memory and Learning Strategies in an Autistic Sample Using the CVLT

Objective:The present study aims to better understand learning strategies and difficulties in autistic youth. Previous studies have found that autistic youth have difficulties with executive function skills and poorer performance in memory and learning tasks, especially those that require spontaneous retrieval of information compared to memory tasks that provide external retrieval cues. Additionally, it has been theorized that autistic youth employ a serial approach rather than a semantic approach to learning. The current study hypothesized that the autistic sample will have (a) significant difficulties in learning and memory, (b) employ a serial approach more frequently and a semantic approach less frequently than the CVLT normative sample, and (c) will benefit significantly when provided with external retrieval cues.Participants and Methods:Archival data from a mixed clinical and research database were examined for this study. Participants include 740 autistic individuals between the ages of 5.50 and 24.3 (M = 10.90, SD = 2.98). The sample consisted of 22.2% girls and 34.0% Black, Indigenous, and people of color (BIPOC). All individuals had a FSIQ &gt; 70 (M = 99.91, SD = 16.09) and were clinically diagnosed with autism using DSM-IV-TR or DSM-V criteria by a clinician at an autism diagnostic center. Participants completed the age-appropriate California Verbal Learning Test (CVLT, Delis et al. 1987) which is a neuropsychological measure that examines verbal memory and learning. One-sample t-tests were used to examine the sample's verbal memory abilities and their learning strategies. A paired sample t-test was used to evaluate the sample's performance before and after an external retrieval cue was given.Results:Results from the one-sample t-tests indicate that the autistic sample performed worse than the CVLT normative data with a large effect size (t(739)= -9.440, p &lt;.001, Cohen's d = 1.292). Secondly, the autistic sample was less likely to use a semantic learning approach (t(739) = -1.841, p = .033, Cohen's d = 1.234), but not more likely to use a serial approach (t(739)=-.040, p=.484) compared to the normative sample. Lastly, the paired sample t-test results show that the sample performed significantly better after receiving the external retrieval cue (t(739)=-2.570, p=.005, Cohen's d = .770).Conclusions:The data supported the first hypothesis; autistic individuals have increased difficulties with learning and verbal memory. However, the data only partially support the second hypothesis. The sample was less likely to use a semantic approach to learning but was not more likely to use serial learning. This finding is opposed to the Weak Central Coherence (WCC) theory, which suggests that autistic individuals are more likely to have detail-oriented, bottom-up cognitive thinking styles, consistent with a serial learning strategy. Lastly, data showed improvement when autistic individuals received a retrieval cue. This result supports the Task Support Hypothesis (TSH) and indicates that autistic individuals benefit from cues for memory recall, particularly those that capitalize on their areas of strength. This study did not use a control group and is limited in ethno-racial diversity; therefore, these are preliminarily findings that require further replication.

10 Comprehensive Neuropsychological Findings in Erdheim-Chester Disease: Case Report

Objective:Erdheim-Chester disease (ECD) is a rare disorder characterized by excessive production and accumulation of histiocytes within multiple tissues and organs. ECD primarily affects adults, and symptoms vary depending upon the specific location and severity. Etiology is not always known, but some patients with ECD may have a non-inherited genetic change that allows histiocytes to reproduce uncontrollably. Currently, the cognitive outcomes of ECD are not well understood, and there are no previous neuropsychological findings in the literature. Thus, the objective of this case study was to describe the neuropsychological presentation and findings of an ECD case to inform diagnosis and treatment better.Participants and Methods:The patient was a 64-year-old white, non-Hispanic, right-handed man diagnosed with ECD in 2017. ECD accounted for a constellation of medical problems, including diabetes insipidus, hypogonadism, and interstitial lung disease. A brain MRI in 2018 revealed orbital nodularities and pituitary infiltration thought to be consistent with ECD. The patient first noticed cognitive functioning difficulties in 2020 primarily related to short-term memory. Approximately two years later, he noted significant cognitive changes, including difficulties recalling recent events, dates, and conversations, problem-solving, and planning. He had difficulty driving and had two recent car accidents when leaving his driveway. Physically, he reported increased fatigue, unsteadiness, and occasional falls. In 2022, he had a brain MRI that demonstrated a progression of multiple diffuse cerebral, cerebellum, and brainstem lesions and cerebral volume loss compared to prior imaging. He was referred for a neuropsychological assessment to rule out a neurodegenerative disorder.Results:Neuropsychological data demonstrated moderate-to-severe deficits on tests of basic spatial working memory, visually based processing speed, visual memory, letter verbal fluency, and semantic verbal fluency. He demonstrated mild-to-moderate deficits on tests of basic auditory attention, verbal memory, higher-level visuospatial processing, abstract nonverbal reasoning, multistep, organization and planning, self-monitoring of performance quality, and fine hand and motor dexterity. He demonstrated variable initial learning of new information across modalities, although he did benefit from structured verbal material. Recognition was variable, with difficulty demonstrated in discriminating visual information presented, from similar competing information, along with availability recalling visual information. He showed average auditory-based divided attention, confrontational object naming, and abstract verbal reasoning. Regarding his emotional functioning, he reported mild depressive and anxiety symptoms.Conclusions:To the best of our knowledge, this is the first report documenting detailed neuropsychological data on this rare disease. The case study documents widespread cognitive deficits with greater difficulty with visually based abilities than verbal abilities. Specifically, patients with ECD may present with cognitive difficulties in visual learning and memory, processing speed, visuospatial processing, select areas of executive/frontal systems, letter and semantic verbal fluency, and fine motor dexterity.

59 Perinatal Risk Factors and Cognitive Outcomes in Children HIV-Exposed, Uninfected

Objective:Children who are HIV-exposed uninfected (CHEU) are at risk of neurodevelopmental impairments due to perinatal HIV and antiretroviral therapy exposure as well as additional health and psychosocial burdens. There is limited understanding of the impact of perinatal risk factors on long-term outcomes of CHEU. The present study investigated the association between perinatal risk factors and the intellectual and language abilities in CHEU and children who are HIV-unexposed uninfected (CHUU).Participants and Methods:CHEU and CHUU, 6 to 10 years, of age underwent neurodevelopmental assessments through the Kids Imaging and Neurocognitive Development (KIND) study at the Hospital for Sick Children in Toronto, Canada between January 2020 and August 2022. CHUU were recruited from the community with similar sociodemographic backgrounds based on residential area in Toronto and parental income levels. Measures of Full-Scale IQ (FSIQ), Verbal Comprehension (VCI), Visual Spatial skills (VSI), Fluid Reasoning (FRI), Working Memory (WMI), and Processing Speed (PSI) were evaluated with the Wechsler Intelligence Scale for Children - Fifth Edition. Core Language, Receptive Language, and Expressive Language skills were assessed with the Clinical Evaluation of Language Fundamentals - Fifth Edition. Perinatal risk factors included birthweight, birth complications (e.g., premature rupture of membranes, jaundice, etc.), maternal smoking and alcohol use during pregnancy, and NICU admission. Analyses of variance and chi-square tests were performed to investigate group differences and multiple regression analyses tested the relation between neurodevelopmental measures and birth factors. Significance was held at p &lt;0.05.Results:36 CHEU (21 female, 8.74 ±1.56 years) and 26 CHUU (12 female, 8.53 ±1.50 years) children were included. For both groups, mean standardized scores of the cognitive abilities assessed were in the average range. CHEU had significantly lower birth weight than CHUU, but there were no differences between these groups with respect to maternal smoking and alcohol use, birth complications or NICU admission. There were no between group differences identified for the intellectual and language abilities. In the CHEU group, birthweight was significantly associated with lower VCI, WMI, and expressive language. In the CHUU group, prenatal alcohol and smoking exposure was associated with lower VCI scores. Birth complications were associated with lower WMI, PSI, and FSIQ scores.Conclusions:In this interim analysis, perinatal risk factors impacted neurodevelopmental outcomes of CHEU and CHUU differently. While the groups did not differ in frequency of birth complications and maternal smoking and alcohol use, these factors negatively impacted aspects of intellectual ability in the CHUU group. CHEU with lower birthweight are at greater risk of working memory and language difficulties, supporting the need for early interventions and close neuropsychological follow-up of this population throughout childhood.

57 Clinical Utility of Neuropsychological Evaluation in the Differential Diagnosis Between Late-Onset Primary Progressive Aphasia Semantic Variant (PPA-SV) Versus Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE): A Case Report

Objective:Primary progressive aphasia semantic variant (PPA-SV) is an atypical dementia subtype on the frontotemporal dementia (FTD) spectrum. PPA-SV is clinically defined by naming and semantic deficits, with progressive language decline that generalizes to other domains over time. Typically, it presents as an early-onset dementia with TDP-43 pathology, but 33-46% of PPA-SV cases display initial onset after age 65 with potentially different clinical features. Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE), a more recently discovered neurodegenerative entity, is defined by an older age of onset, hippocampal sclerosis/atrophy, and TDP-43 pathology with a gradually progressive amnestic profile that expands to other cognitive deficits over time. The authors present a case report with overlapping features and suspected TDP-43 neuropathology ante-mortem for two reasons: first, to highlight the need for clinical criteria to formally diagnose LATE, and second, to address a gap in the literature on the possible clinical differences of late-onset PPA-SV.Participants and Methods:The authors present a case of a 78-year-old Indian bilingual man (English dominant) with 18 years of education, noncontributory medical history, and gradually progressive cognitive complaints reported over the past few years who was seen for outpatient neuropsychological evaluation. Prior workup was notable for negative amyloid PET scan, negative p-tau 217 blood test, and abnormal brain MRI revealing marked bilateral hippocampal atrophy with ex vacuo ventriculomegaly and minimal cerebrovascular disease. He scored 23/30 on prior MMSE, was diagnosed with amnestic MCI, prescribed Namenda and Exelon, and complained of minor memory and word-finding difficulties with reportedly intact IADLs and no signs of NPH.Results:Neuropsychological testing revealed a profound dysnomia (RBANS Naming raw score = 1/10), and he provided 0 words on two semantic fluency tasks but 15 words on letter fluency. Receptive vocabulary score was also impaired (PPVT-4, &lt;1st %). Memory performance also demonstrated rapid forgetting of information (RBANS List Recall raw = 0/10, Story Recall raw = 0/12) with no benefit to recognition cues (RBANS List Recognition raw = 12/20), but slightly better visual memory recall, albeit still impaired (RBANS Figure Recall raw = 4/20). Grooved pegboard scores were significantly worse with right-hand than left-hand. Irregular word reading (NAART = 16th %ile) was significantly below expectations and thought to reflect more of a surface dyslexia rather than a cultural confounder given that he has lived in the US for over 50 years and his occupational and educational history was completed in English.Conclusions:Results support the clinical utility of neuropsychological evaluation in the differential diagnosis to support a predominant clinical syndrome of PPA-SV despite overlapping features with LATE and suspected TDP-43 pathology. This case report highlights the diagnostic issue with the lack of literature describing the typical clinical progression or suggested diagnostic criteria of LATE. These findings also indicate that late-onset PPA-SV may include greater memory deficits earlier in the course, but this may also be a clinical masquerade that is more reflective of the extent of language deficits. Further research on late-onset manifestations of PPA-SV and LATE consensus clinical guidelines is advised.

12 AppReminders - A pilot feasibility randomised controlled trial of a memory aid app for people with acquired brain injury

Objective:Mobile phone reminding apps can be used by people with acquired brain injury (ABI) to compensate for their memory impairments. However off-the-shelf apps may be difficult to use. ApplTree has been developed to be accessible to this group, compared to off-the-shelf reminding apps such as Google Calendar. This pilot feasibility trial aimed to establish the feasibility of running (and issues that should be addressed to complete) a randomised controlled trial comparing ApplTree to Google Calendar in an ABI community treatment setting.Participants and Methods:Adults with self or other reported memory difficulty after an ABI were enrolled (n=39). Those who completed the baseline phase were randomised (n=29) and randomly allocated to the Google Calendar or ApplTree intervention. They were shown a 30 minute video tutorial of the app and an assessment on their ability to use it. Timely completion of everyday memory tasks were measured for a 3 week pre-intervention baseline and 3 week post-intervention follow-up phase. Participants also completed neuropsychological tests assessing memory, attention and executive function and gave qualitative feedback on the app and their experience in the trial.Results:Recruitment rate was 58% of the target (29 were randomised, n=50 was the target in 2 years). Retention rate was 65.5% and adherence rate was 57.9%. While the feasibility trial was not powered to calculate efficacy, there was a 13% increase in everyday memory tasks completed on time for those in the ApplTree group (n=10) compared to baseline and no change for the Google Calendar group (n=9). Feasibility results indicate 72 participants would need to fully complete a trial to detect the minimum clinically important difference (12.5% increase in successful performance of everyday memory tasks) in the efficacy of ApplTree compared to Google Calendar, should such a difference exist.Conclusions:The challenges with recruitment of people receiving community care for ABI are highlighted in this trial and discussed along with the impact of the Covid-19 pandemic. Methodological considerations for researchers or clinicians looking to measure everyday memory ability are discussed. The majority (19 of 21) of participants who were given an app were capable of learning to use it during an hour-long session. This indicates it is a feasible intervention that community ABI services could offer. Participant feedback highlighted the merits of design features implemented in ApplTree that can improve the uptake and utility of reminding apps.

49 Case Study: Cognitive Deficits Associated with Norrie Disease

Objective:Norrie disease is a rare, x-linked recessive genetic disorder associated with an NDP gene mutation. Males are predominantly affected. Typical symptoms include vision loss around the time of birth and progressive hearing loss. Cognitive and behavioral abnormalities also occur in 30-50% of individuals, including developmental delays, intellectual disability, cognitive regression, psychosis, and aggression. There is limited research, however, examining the neuropsychological deficits in adulthood resulting from Norrie disease, especially with neuropsychological data and in individuals without other neurological manifestations of the disease, such as seizures. Here, we present the neurocognitive profile of a patient with Norrie disease who presented for a cognitive evaluation in adulthood due to report of more recent memory decline.Participants and Methods:Mr. Smith is a Caucasian male in his mid-40's who previously underwent genetic testing and was subsequently diagnosed with Norrie disease. As a result of his diagnosis, he experienced complete vision loss since birth and bilateral hearing loss that began in childhood and gradually worsened in adolescence. Medical history was otherwise unremarkable. Developmental milestones were met on time. Historical intelligence testing conducted in elementary school revealed borderline on one intelligence test to high average performance on other intelligence tests. However, he was retained grades several times due to factors such as behavioral disruptions and academic difficulties. He had been employed as an assembly line worker for many years, but had not worked for 10 years prior to the neuropsychological evaluation. Emotionally, he had a longstanding history of anxiety and endorsed mild anxiety and depression at the time of the evaluation. The patient first noticed memory difficulties in adolescence then noticed further decline four years prior to the neuropsychological evaluation (around when he received a left-ear cochlear implant), which had remained stable since onset.Results:In the context of low average premorbid intellectual functioning, Mr. Smith's neurocognitive profile was notable for difficulties with alphanumeric set-shifting and abstract thinking, with otherwise preserved cognitive functioning. Weaknesses observed on testing may have represented longstanding weaknesses and did not rise to the level of a cognitive disorder. Affective distress was also suspected to have accounted for some of the cognitive lapses the patient reported experiencing with day-to-day functioning.Conclusions:The current poster aims to contribute to the limited body of literature examining neuropsychological deficits in adulthood resulting from Norrie disease. This is especially critical given that the long-term cognitive dysfunction of this disorder is relatively unknown and could negatively impact patients' quality of life over time.

52 Stable Cognitive Impairment and Increased Psychiatric Symptoms in a Patient with Neuropathologically Progressive Fahr’s Disease After 2-Year Repeated Neuropsychological Assessment

Objective:Fahr’s disease is a rare genetic neurological disorder characterized by abnormal idiopathic calcification of the basal ganglia, typically with extrapyramidal symptoms, speech difficulty, behavioral disturbances, and progressive neurologic dysfunction. A small number of case reports have explored the neuropsychological profile of Fahr’s disease patients, and even fewer have followed the course of neuropsychological functioning over time.Participants and Methods:A 53-year-old Asian woman presented for a neuropsychological reevaluation (2021) after experiencing a recurrence of memory difficulties and mood changes. Relevant medical history was significant for systemic lupus erythematosus (SLE) and Fahr’s disease. Following an episode of acute confusion, the patient underwent a head CT (2019) which revealed extensive calcification throughout the cerebellum, central pons, and periventricular and subcortical white matter, suggestive of Fahr’s disease. Two months later, she underwent an initial neuropsychological evaluation (2019), which demonstrated prominent attention and processing speed deficits contributing to variably impaired new learning and memory along with spatial planning and problem-solving difficulties. The etiology of her cognitive deficits was determined to likely reflect metabolic and immune instability, consistent with her history of SLE and Fahr’s disease. An updated CT (2021) revealed increased calcification throughout the bilateral corona radiata, basal ganglia, cerebellar hemispheres, and midbrain, which was determined to be compatible with progressive Fahr’s disease.Results:The patient’s neurocognitive profile from current neuropsychological testing (2021) was marked by notable deficits in attention and processing speed, delayed memory, problem solving, visuospatial reasoning, and motor dexterity. Compared to her initial evaluation, her cognitive profile remained stable save for a slight decline in processing speed. The largest change was seen within the psychiatric domain. Self-reported depressive symptoms involving anhedonia, concentration difficulties, and anxiety symptoms involving nervousness and tension were more pronounced in her current evaluation. In addition, she endorsed an increase in apathy compared to her initial evaluation.Conclusions:The cognitive profile seen in this patient is consistent with the current literature relating to the clinical sequelae of Fahr’s disease in patients that eventually went on to develop dementia. Despite an increase in brain calcification seen on CT imaging over an 18-month interval, the patient’s neurocognitive profile remained relatively stable. An increase in psychiatric symptoms appeared to be the most prominent change over repeated neuropsychological assessment, which elucidates the heterogenous course of Fahr’s disease from a neuropsychological perspective. Further exploration of this disorder is warranted to better understand the clinical progression of symptoms over time.

3 Separating Memory Impairment from Other Neuropsychological Deficits on the CVLT-II

Objective:Learning curve patterns on list-learning tasks can help clinicians determine the nature of memory difficulties, as an “impaired” score may actually reflect attention and/or executive difficulties rather than a true memory impairment. Though such pattern analysis is often qualitative, there are quantitative methods to assess these concepts that have been generally underutilized. This study aimed to develop a model that decomposes learning over repeated trials into separate cognitive processes and then include other testing data to predict performance at each trial as a function of general cognitive functioning.Participants and Methods:Data for CVLT-II learning trials were obtained from an outpatient neuropsychology service within an academic medical center referred for clinical reasons. Participants with a cognitive diagnosis of non-demented (ND) or probable Alzheimer’s disease (AD) were included. The final sample consisted of 323 ND [Mage = 58.6 (14.8); Medu = 15.4 (2.7); 55.7% female] and 915 AD [Mage = 72.6 (9.0); Medu = 14.2 (3.1); 60.1% female cases. A Bayesian non-linear beta-binomial multilevel model was used, which uses three parameters to predict CVLT-II recall-by-trial: verbal attention span (VAS), maximal learning potential (MLP), and learning rate (LR). Briefly, VAS predicts expected first trial performance while MLP, conversely, predicts the expected best performance as trials are repeated, and LR weights the influence of VAS versus MLR over repeated trials. Predictors of these parameters included age, education, sex, race, and clinical diagnosis, in addition to raw scores on Trail Making Test Parts A and B, phonemic (FAS) fluency, animal fluency, Boston Naming Test, Wisconsin Card Sorting Test (WCST) Categories Completed, and then age-adjusted scaled scores from WAIS-IV Digit Span, Block Design, Vocabulary, and Coding. Random intercepts were included for each parameter and extracted for comparison of residual differences by diagnosis.Results:The model explained 84% of the variance in CVLT-II raw scores. VAS reduced with age and time-to-complete Trails B but improved with both verbal fluencies and confrontation naming. MLP increased as a function of WAIS Digit Span, animal fluency, confrontation naming, and WCST categories completed. Finally, LR was greater for females and WAIS-IV Coding and Vocabulary performances but reduced with age. Participants with AD had lower estimates of all three parameters: Cohen’s d = 2.49 (VAS) - 3.48 (LR), though including demographic and neuropsychological tests attenuated differences, Cohen’s d = 0.34 (LR) - 0.95 (MLP).Conclusions:The resulting model highlights how non-memory neuropsychological deficits affect list-learning test performance. At the same time, the model demonstrated that memory patterns on the CVLT-II can still be identified beyond other confounding deficits since having AD affected all parameters independent of other cognitive impairments. The modeling approach can generate conditional learning curves for individual patient data, and when multiple diagnoses are included in the model, a person-fit statistic can be computed to return the mostly likely diagnosis for an individual. The model can also be used in research to quantify or adjust for the effect of other patient data (e.g., neuroimaging, biomarkers, medications).

Understanding nonliteral language abilities in children with neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) is a genetic syndrome that affects cognitive, behavioral, and social development. Nonliteral language (NLL) comprehension has not been examined in children with NF1. This study examined NLL comprehension in children with NF1 and associated neuropsychological correlates. NLL comprehension was examined in children with NF1 (n = 49) and typically developing (TD) controls (n = 27) aged 4-12 years using a novel NLL task. The task assessed comprehension of sarcasm, metaphor, simile, and literal language. Cognitive (Wechsler Scales Composites or the Woodcock-Johnson Test of Cognitive Abilities Revised scaled scores) and behavioral (attention deficit hyperactivity disorder [ADHD] symptoms) correlates of NLL comprehension in children with NF1 were also examined. Children with NF1 demonstrated significantly poorer sarcasm comprehension than TD children and a vulnerability in metaphor comprehension. Simile and literal language comprehension were not significantly different between groups. Working memory difficulties and impulsive/hyperactive ADHD symptoms were associated with a reduced ability to identify sarcasm in NF1, while verbal comprehension, fluid reasoning, and inattentive ADHD symptoms were not. Results suggest children with NF1 experience challenges in understanding complex NLL comprehension, which are related to reduced working memory and increased impulsivity/hyperactivity. This study provides an initial insight into the figurative language abilities of children with NF1, which should be examined in relation to their social difficulties in future studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

68 Associations between within-domain intraindividual variability and functional abilities in cognitively healthy older adults

Objective:Cognitive performance, particularly in the domains of memory and executive functioning (EF), have been shown in previous research to predict decline in everyday functioning in older adults. The goal-control model posits that episodic memory difficulties cause weak or decaying task goals that lead to the omission of every day task steps (low accomplishment). EF difficulties preclude control over the execution of task goals that lead to inefficient and error-prone performance (high errors). Intraindividual variability (IIV) in neuropsychological test performance has been proposed as a noninvasive early marker of dementia and has utility in cognitively healthy older adults. In this study we examined cross-sectional relations between within-domain IIV in memory and attention/EF with performance of everyday tasks in the lab. We expected greater memory IIV to be associated with task accomplishment (goal decay), and greater attention/EF IIV to be associated with errors (poor control over goals).Participants and Methods:40 cognitively normal (CN) older adult (65+) participants (M age=71.44, SD=10.62; 73.8% women; 85.7% White; M education=18.55, SD=8.38) completed the Naturalistic Action Test (NAT), requiring completion of standardized, everyday tasks (i.e., breakfast, lunch) and scored for accomplishment of steps and various errors (micro-errors - misreach to distractor object, extra actions; overt -sequence, perseverative behaviors, etc.; motor errors). Within-domain IIV measures were calculated for 6 memory measures (HVLT-R, BVMT-R) and 6 attention/EF measures (Digit Span, Trail Making Test, Salthouse Letter/Pattern Comparison). First, raw scores for each test were z-transformed, then the intraindividual standard deviation of all z-scores was calculated. Bivariate Spearman’s rank-order correlations were used to examine associations between NAT performance and within-domain IIV, as well as mean performance. Linear regressions were used to examine the associations of IIV score with NAT scores, adjusting for age, sex, and mean cognitive performance.Results:Among CN participants, higher memory IIV was significantly associated with lower NAT accomplishment (r=-.329, p=.038), and better mean memory performance was significantly associated with fewer errors (micro-errors r=-.509, p=.003; overt r=-.438, p=.012; motor errors r=-.463, p=.008). Regression models revealed that memory IIV, after controlling for mean memory performance, age, and sex, did not significantly predict NAT performance. High attention/EF IIV was significant associated with more errors (overt r=.377, p=.016), whereas mean attention/EF performance was not significantly correlated with any NAT measures. Attention/executive function IIV significantly predicted errors (micro-errors B=4.15, p=.03; Overall model: R2=0.285, F(4, 24)=2.393, p=.079; overt B=.562, p=.032; Overall model: R2=0.371, F(4, 24)=3.543, p=.021) after adjusting for mean attention/executive function performance, age, and sex.Conclusions:Consistent with the goal-control model framework, greater variability in memory was associated with lower task accomplishment, whereas greater variability in attention/EF was associated with more errors. However, only attention/EF IIV predicted NAT performance, specifically errors (micro-errors, overt errors), after adjusting for age, sex, and mean attention/EF performance. Within-domain IIV can be used to predict mild functional difficulties in cognitively healthy older adults. Future research should examine within-domain IIV in a larger sample with more diversity to maximize generalizability, and in a longitudinal design to evaluate within-domain IIV predictive validity for cognitive/functional impairment.

36 Assessing the Effect of Multiple Sclerosis and Aging Using an Ecological test of Prospective Memory

Objective:Prospective memory (PM) is the ability to remember to produce an action at a specific moment in the future signaled by the occurrence of a specific event (EB condition), a time or a time interval (TB condition). Detection of the appropriate moment corresponds to the prospective component (PC), while production of the appropriate action corresponds to the retrospective (RC) component. Although PM difficulties have been reported in healthy aging and in association with Multiple Sclerosis (MS), PM has not been examined in elderly people with MS (PwMS), which is particularly relevant since their life expectancy has improved significantly in recent years due to available treatments, and PM is essential to daily functioning. The main objective of this study was to investigate whether the decline in PM performance with advancing age is influenced by the presence of multiple sclerosis (MS). This study also aimed to clarify the type of PM impairment (PC vs RC in TB and EB conditions) in MS as a function of age.Participants and Methods:A total of 80 participants were recruited and separated into four groups: elderly PwMS (n = 20), young PwMS (n = 20), elderly healthy controls (HC) (n = 20) and young HC (n = 20). PM and its components were measured using the TEMP, an experimental ecological tool developed by our laboratory that has been validated in previous studies. In addition, all participants underwent a series of neuropsychological tests specific to MS (MACIFMS) and aging (Boston Naming Test, Clock Drawing Test, Towers of London, Trail making Test, Stroop, MoCA).Results:On the TEMP total score, a two-way ANOVA showed a main effect of age (F[1,75]=47.4, p&lt;0.001, n2 = .40), a main effect of the presence of MS (F[1,75]=19.51, p&lt;0.001, n2 = .21) as well as a significant Age X Disease interaction (F[2,74] =5.40, p=0.023, n2 = .07). Direct comparison between EB and TB conditions revealed that for the PC, only elderly PwMS had more difficulty in the TB than in the EB condition (Z = -2.51, p = 0.012), whereas RC score was significantly lower in the TB than in the EB condition in all groups except in younger controls (younger PwMS : Z = -2.56, p = 0.01; elderly HC : Z = -3.31, p &lt; 0.001; elderly PwMS :Z = -3.04, p = 0.002).Conclusions:The TEMP revealed a marked impairment in PM in elderly PwMS compared to elderly HC and young PwMS. This impairment was particularly evident on the PC component in the TB condition. RC difficulties noted in the TB condition in all but younger controls reflect the arbitrary nature of the cue-action link that is particularly sensitive to episodic memory difficulties often observed in aging and MS.

Age differences in inhibitory and working memory functioning: limited evidence of system interactions

ABSTRACT Debate persists regarding the nature of age-related deficits in inhibition, and whether inhibitory functioning depends on working memory systems. The current research aimed to measure age-related differences in inhibition and working memory, characterize the relationship between inhibitory functions and working memory performance, and determine how these relationships are affected by age. Toward these ends, we measured performance on a range of established paradigms in 60 young adults (18–30 years) and 60 older adults (60–88 years). Our findings support age-related increases in reflexive inhibition (based on the fixation offset effect and inhibition of return) and age-related decrements in volitional inhibition (based on several paradigms: antisaccade, Stroop, flanker, and Simon). This evidence of stronger reflexive inhibition combined with weaker volitional inhibition suggests that age-related deterioration of cortical structures may allow subcortical structures to operate less controlled. Regarding working memory, older adults had lower backward digit scores and lower forward and backward spatial scores. However, of the 32 analyses (16 in each age group) that tested for dependence of inhibitory functioning on working memory functioning, only one (in young adults) indicated that inhibition performance significantly depended on working memory performance. These results indicate that inhibition and working memory function largely independently in both age groups, and age-related working memory difficulties cannot account for age-related declines in inhibitory control.