Comprehensive Neuropsychological Evaluation Research Articles

Comparison of decline in different cognitive domain in patients with normal pressure hydrocephalus

We sought to describe the cognitive profile of patients with Idiopathic Normal Pressure Hydrocephalus (iNPH) using a comprehensive neuropsychological battery. Based on age and education correlated norms, we aimed to compare performance in each measured cognitive domain: executive functions (EFs), verbal memory (VM), non-verbal memory (nVM), visuoconstructional abilities (VA) and attention/psychomotor speed (A/PS). Patients diagnosed with iNPH underwent comprehensive neuropsychological evaluation before shunting. Their performance was compared to the age and education correlated norms. Correlation of different cognitive domains in iNPH profile was performed. A total of 53 iNPH patients (73.21 ± 5.48 years) were included in the study. All of the measured cognitive domains were significantly damaged. The most affected domains were EFs and VM (p<0.001 and p<0.001, respectively). A/PS domain was affected milder than EFs and VM (p<0.001). The least affected domains were nVM (p<0.001) and VA (p<0.001). Patients with iNPH are affected in all cognitive domains and the cognitive decline is uneven across these domains. The impairment of memory was shown to depend on the presented material. VM was shown to be much more severely affected than nVM and along with VM, EFs were shown to be the most affected. A/PS speed was shown to be less affected than VM and EFs and the least affected domains were nVM and VA.

Low Functional network integrity in cognitively unimpaired and MCI subjects with depressive symptoms: results from a multi-center fMRI study

Evidence suggests that depressive symptomatology is a consequence of network dysfunction rather than lesion pathology. We studied whole-brain functional connectivity using a Minimum Spanning Tree as a graph-theoretical approach. Furthermore, we examined functional connectivity in the Default Mode Network, the Frontolimbic Network (FLN), the Salience Network, and the Cognitive Control Network. All 183 elderly subjects underwent a comprehensive neuropsychological evaluation and a 3 Tesla brain MRI scan. To assess the potential presence of depressive symptoms, the 13-item version of the Beck Depression Inventory (BDI) or the Geriatric Depression Scale (GDS) was utilized. Participants were assigned into three groups based on their cognitive status: amnestic mild cognitive impairment (MCI), non-amnestic MCI, and healthy controls. Regarding affective symptoms, subjects were categorized into depressed and non-depressed groups. An increased mean eccentricity and network diameter were found in patients with depressive symptoms relative to non-depressed ones, and both measures showed correlations with depressive symptom severity. In patients with depressive symptoms, a functional hypoconnectivity was detected between the Anterior Cingulate Cortex (ACC) and the right amygdala in the FLN, which impairment correlated with depressive symptom severity. While no structural difference was found in subjects with depressive symptoms, the volume of the hippocampus and the thickness of the precuneus and the entorhinal cortex were decreased in subjects with MCI, especially in amnestic MCI. The increase in eccentricity and diameter indicates a more path-like functional network configuration that may lead to an impaired functional integration in depression, a possible cause of depressive symptomatology in the elderly.

Design of a video game for assessment of executive functions in deaf and hearing children

This study investigates the effectiveness of a computerized cognitive test battery embedded within a video game to assess executive functions (EF) in deaf and hearing children. We evaluated a diverse cohort of 290 elementary school students aged 5 to 13 years (mean age = 8.86, SD = 1.96), comprising 74 sign language users, 14 Spanish-speaking deaf participants, 23 children with mixed communication methods, and 179 typically hearing individuals. Our statistical analysis focused on item discrimination, reliability, and criterion validation of the game-based assessments. The results indicated high reliability and effective discrimination of EF across the game’s three primary stages. External validation was conducted using the Matrices Test, educational attainment, and age as variables. A significant positive correlation (r = 0.377, p < 0.001) was observed between the Matrices Test scores and game-based achievement scores. Furthermore, linear regression analysis revealed education (Standardized Beta = 0.339) and age (Standardized Beta = 0.179) as significant predictors of performance in these scores. This study underscores the value of integrating computerized cognitive assessments within a video game environment for comprehensive neuropsychological evaluations, highlighting its potential in diverse child populations.

Repeated surgical resections for management of high-grade glioma and its impact on quality of life.

High-grade gliomas (HGG) are aggressive cancers, and their recurrence is inevitable, despite advances in treatment options. While repeated tumor resection has been shown to increase survival rate, its impact on quality of life is not clearly defined. To address this gap, we compared quality of life (QoL) changes in HGG patients who underwent first-time (FTR) versus repeat surgical resections (RSR) for management of recurrence. Forty-four adults with HGG who underwent tumor resection were included in this study and classified into either the FTR group (n = 23) or the RSR group (n = 21). All patients completed comprehensive neuropsychological evaluations that included the Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scales, pre-operatively and at two weeks post-operatively. There was no difference between the FTR and RSR groups in any of the QoL indices (all p > .05), except for improved emotional well-being and worsened social well-being, suggesting minimal detrimental effects of repeat surgeries on QoL in comparison to first time surgery. These results suggest that repeated resection is a viable strategy in certain cases for management of HGG recurrence, with similar impact on QoL as observed in patients undergoing first time surgery. These encouraging outcomes provide useful insight to guide treatment strategies and patient and clinician decision making to optimize surgical and functional outcomes.

Abstract TP18: A 15-Minute Cognitive Screen Identifies Post-Stroke Cognitive Impairment

Introduction: While comprehensive neuropsychological evaluations are a valuable part of post-stroke care, time-intensive assessments may not always be feasible or well-tolerated in certain clinical settings. There is a need for a brief cognitive battery that can detect post-stroke cognitive impairment while being efficient with regard to time and resources. Methods: As part of the parallel StrokeCog and Stroke-IMPaCT studies, 127 participants with chronic ischemic stroke completed comprehensive neuropsychological testing at Stanford. They underwent a cognitive battery consisting of 13 tests that encompassed 5 cognitive domains. Partial least square analyses identified a set of candidate tests that were most associated with cognitive impairment on this comprehensive battery, defined as 2 domain z-scores &lt;-1 or 1 domain z-score &lt;-1.5. We used these candidate tests to construct a brief battery of 5 tests (StrokeCog-Brief). Psychometric properties were compared amongst StrokeCog-Brief, the MoCA, and another established 30-minute battery (NINDS-30). Initial findings were cross-validated in an independent sample of 61 participants at University of Manchester. Results: The StrokeCog-Brief battery consisted of 5 measures of language, working memory, learning, and attention/processing speed (HVLT Immediate Recall, Trails A, Trails B, Digit Span Forward/Backward, Phonemic Fluency) that took approximately 15 minutes to complete. StrokeCog-Brief demonstrated high sensitivity (0.97) and adequate specificity (0.78) in detecting cognitive impairment on the comprehensive battery, outperforming both the MoCA (0.77, 0.73) and NINDS-30 (0.97, 0.35). In the cross-validation sample, StrokeCog-Brief similarly demonstrated high sensitivity (0.93) and adequate specificity (0.67), again outperforming both the MoCA (0.60, 0.86) and NINDS-30 (0.81, 0.08). Conclusions: We identified a brief, 15-minute battery of 5 tests that has high sensitivity in detecting cognitive impairment in people who have had a stroke. This brief battery covers multiple cognitive domains commonly impacted by stroke and represents an efficient means to identify chronic post-stroke cognitive impairment.

Factors Associated with Cognitive Impairment in Patients with Persisting Sequelae of COVID-19

ObjectiveQuantify cognitive deficits in patients with postacute sequelae of COVID-19 (PASC) and identify key variables related to cognitive impairment in PASC. MethodPatients with polymerase chain reaction-confirmed COVID-19 underwent a comprehensive neuropsychological evaluation. The comparison group included patients without neurological disorders determined by the neuropsychologist to be cognitively intact. Cognitive impairment was defined as impairment (Composite T ≤35) in 1 of 6 cognitive domains. The PASC group was split into impaired or intact based on the above criteria. Multivariable logistic regression models assessed predictors including demographics, COVID-19 severity, clinical characteristics, and mood. ResultsThere were 210 patients with PASC, predominantly female (73.3%, P < .001), without other demographic differences when compared with 369 normal controls. Patients with PASC were more likely to have cognitive impairment (odds ratio 3.61; 95% confidence interval, 2.36-5.54; P < .001) compared with controls, with significantly lower scores in domains of memory, language, processing speed, visuospatial function, executive function (P < .001), and higher depressive (P = .004) and anxiety symptoms (P = .003). Patients with PASC who demonstrated cognitive impairment (n = 93) had higher body mass index compared with those with PASC without cognitive impairment (n = 117), without differences in other predictors. ConclusionPatients with PASC are almost 4 times more likely to evidence cognitive dysfunction compared with normal controls. Forty-four percent of patients with PASC demonstrated cognitive deficits about 7 months from infection. Estimated premorbid intelligence significantly correlated with impairment. Higher body mass index was the only metric shown to differentiate those with PASC and cognitive impairment from those with PASC who were cognitively intact.

Five Digit Test in neuropsychological assessment of working memory in aged individuals:normative data.

To provide validity evidence for FDT in the neuropsychological assessment of working memory in the aged. A total of 100 subjects, aged between 56 and 86 years, representing both genders with varying levels of education, underwent a comprehensive clinical history and neuropsychological evaluation using FDT. The mean age of participants was 71.04 years, with 67.3% having intermediate education. Participants were categorized into two groups: Control Group and Cognitive Decline Group. To establish validity evidence, FDT scores (both time and errors) were correlated with the WAIS-III Digits scale. Spearman's correlation coefficient and ROC curve methodology were employed to determine psychometric properties. A significant and moderate negative correlation was evident between FDT Shifting (number of errors) and Digits score (rho=-0.51; p<0.0001), Direct Order (rho=-0.39; p<0.0001), and Indirect Order (rho=-0.46; p<0.0001). The area under the curve was higher for FDT Shifting (errors) (AUC=0.935) for a cutoff point greater than or equal to 5 points, compared to Digits (AUC=0.748). The assessment of the number of errors in FDT Shifting appears to be a statistically significant tool for evaluating working memory impairment in the aged.

Application of a Standardized Treatment Paradigm as a Strategy to Achieve Optimal Onco-Functional Balance in Glioma Surgery.

Gliomas, characterized by their invasive persistence and tendency to affect critical brain regions, pose a challenge in surgical resection due to the risk of neurological deficits. This study focuses on a personalized approach to achieving an optimal onco-functional balance in glioma resections, emphasizing maximal tumor removal while preserving the quality of life. A retrospective analysis of 57 awake surgical resections of gliomas at the National University Hospital, Singapore, was conducted. The inclusion criteria were based on diagnosis, functional boundaries determined by direct electrical stimulation, preoperative Karnofsky Performance Status score, and absence of multifocal disease on MRI. The treatment approach included comprehensive neuropsychological evaluation, determination of suitability for awake surgery, and standard asleep-awake-asleep anesthesia protocol. Tumor resection techniques and postoperative care were systematically followed. The study included 53 patients (55.5% male, average age 39 years), predominantly right-handed. Over half reported seizures as their chief complaint. Tumors were mostly low-grade gliomas. Positive mapping of the primary motor cortex was conducted in all cases, with awake surgery completed in 77.2% of cases. New neurological deficits were observed in 26.3% of patients at 1 month after operation; most showed significant improvement at 6 months. The standardized treatment paradigm effectively achieved an optimal onco-functional balance in glioma patients. While some patients experienced neurological deficits postoperatively, the majority recovered to their preoperative baseline within 3 months. The approach prioritizes patient empowerment and customized utilization of functional mapping techniques, considering the challenge of preserving diverse languages in a multilingual patient population.

Association of Serum Liver Enzymes with Brain Amyloidopathy and Cognitive Performance.

Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation and neurofibrillary tangles in the brain. Emerging evidence has suggested potential interactions between the brain and periphery, particularly the liver, in regulating Aβ homeostasis. This study aimed to investigate the association of serum liver enzymes with brain amyloidopathy and cognitive performance in patients with complaints of cognitive decline. A total of 1,036 patients (mean age 74 years, 66.2% female) with subjective cognitive decline, mild cognitive impairment, AD dementia, and other neurodegenerative diseases were included using the Smart Clinical Data Warehouse. Amyloid positron emission tomography (PET) imaging, comprehensive neuropsychological evaluations, and measurements of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, and albumin, were assessed. After propensity score matching, logistic and linear regression analyses were used to investigate the associations between liver enzymes, amyloid status, and cognitive performance. Additionally, a machine learning approach was used to assess the classification performance of liver enzymes in predicting amyloid PET positivity. Lower ALT levels and higher AST-to-ALT ratios were significantly associated with amyloid PET positivity and AD diagnosis. The AST-to-ALT ratio was also significantly associated with poor memory function. Machine learning analysis revealed that the classification performance of amyloid status (AUC = 0.642) for age, sex, and apolipoprotein E ɛ4 carrier status significantly improved by 6.2% by integrating the AST-to-ALT ratio. These findings highlight the potential association of liver function on AD and its potential as a diagnostic and therapeutic implications.

The Rapid Access Memory Program for Addressing Concerns of Incipient Dementia in Academic Primary Care Settings.

Expedient diagnosis of incipient dementia is often hindered by time constraints in primary care visits, shortage of dementia specialists, and extended waitlists for comprehensive neuropsychological evaluations. We developed the Rapid Access Memory Program (RAMP) to improve access of neuropsychological services for older adults presenting to our institutional primary care clinics with concerns of cognitive decline. RAMP provides abbreviated neurocognitive assessment, same-day patient feedback, expedited reporting to referring providers, and is financially self-supported. Here, we describe development of RAMP and clinical outcomes from the first 3 years. Of 160 patients seen, dementia was diagnosed in 30% and Mild Cognitive Impairment in 50%; Alzheimer's disease was the most common suspected etiology. New psychiatric diagnosis was made in about one-third (n = 54). Most frequent recommendations involved medication adjustments (initiating cholinesterase inhibitors, deprescribing anticholinergics), safety (driving, decision-making), and specialist referrals. Additionally, 27 (17%) subsequently enrolled in local research. Results support feasibility and utility of RAMP for connecting older adults in primary care with neuropsychological services.

Characterization of de novo Dementia with Lewy Body with different duration of rapid eye movement sleep behavior disorder

BackgroundCognitive disorder, parkinsonism, autonomic dysfunction (AuD) and rapid eye movement sleep behavior disorder (RBD) can occur prior to or simultaneously with Dementia with Lewy Body (DLB) onset. RBD is generally linked with progressive neurodegenerative traits. However, associations between RBD with DLB, RBD without DLB, and RBD duration effects on DLB symptoms remain unclear. ObjectivesTo examine DLB symptom frequency and subtypes in RBD, and explore the effects of different RBD onset times on symptoms in de novo DLB patients. MethodsIn this multicenter investigation, we consecutively recruited 271 de novo DLB patients. All had standardized clinical and comprehensive neuropsychological evaluations. Subgroup analyses, performed based on the duration of RBD confirmed by polysomnography before the DLB diagnosis, we compared the proportion of patients with cognitive impairment, parkinsonism, and AuD features between groups. ResultsParkinsonism and AuD incidences were significantly elevated in DLB patients with RBD when compared with patients without RBD. Subgroup analyses indicated no significant differences in parkinsonism between DLB patients who developed RBD ≥10 years prior to the DLB diagnosis and DLB patients without RBD. The incidence of non-tremor-predominant parkinsonism and AuD was significantly higher in DLB patients whose RBD duration before the DLB diagnosis was <10 years when compared with DLB patients without RBD. ConclusionsWe identified significant symptom and phenotypic variability between DLB patients with and without RBD. Also, different RBD duration effects before the DLB diagnosis had a significant impact on symptomatic phenotypes, suggesting the existence of a slowly progressive DLB neurodegenerative subtype.

PERSONALIZED DEMENTIA PREVENTION IN LUXEMBOURG: INSIGHTS INTO THE PROGRAMME DEMENTIA PREVENTION (PDP)

Abstract BACKGROUND Given that in an increasingly ageing society, the number of people with cognitive impairment is expected to increase, prevention strategies to reduce the high personal and societal burden of neurodegenerative diseases leading to dementia is of essence. METHODS As part of the “Dementia Prevention Programme (pdp)” in Luxembourg, individuals with Mild Cognitive Impairment (MCI) or Subjective Cognitive Decline (SCD) are recruited via referring physicians and other sources. All participants undergo a comprehensive neuropsychological evaluation and a risk factor profile is created. Factors known to increase the risk to develop dementia include hypertension, hypercholesterolaemia, physical or cognitive inactivity, depression, social isolation or hearing loss. Based on the results of this analysis, personalised lifestyle interventions are recommended to each participant, such as cognitive training, physical activities, psychological counselling or nutritional advice. RESULTS To date, 491 participants (mean age = 69.0 years; SD = 11.2) have been recruited at various sites across the country, of whom 424 (86.4%) present with MCI and 42 (8.6%) with SCD. 25 participants (5.1%) showed more advanced cognitive difficulties associated with loss of autonomy or had neither subjective nor objective cognitive difficulties and thus did not belong to the target group. CONCLUSION We provide evidence for the successful implementation of a nationwide dementia prevention programme and efficient recruitment of the target population by building a network of different health care providers. This may serve other countries as an example to rule out similar programmes targeting at promoting healthy ageing among the general population.

Trastorno por déficit de atención e hiperactividad: perfil neuropsicológico y estudio de su impacto en las funciones ejecutivas y académicas

IntroductionThe aim of the study was to describe the neuropsychological profile of patients with attention deficit hyperactivity disorder (ADHD) and the impact of the disorder on executive functioning and academic performance. Patients and methodsWe conducted a retrospective observational and analytical study. The sample consisted of 24 children with a diagnosis of ADHD (aged 6-15 years) without pharmacological treatment and 24 controls without ADHD (aged 7-15 years). A comprehensive neuropsychological evaluation was carried out, encompassing major cognitive domains, in addition to assessment of executive functioning and psychopathological symptoms through the administration of questionnaires to parents and teachers. ResultsThe cognitive profile of the ADHD group was characterized by overall scores (including executive functions and academic abilities) in the normal range (z scores between −1 and 1), although significantly lower compared to the control group. Over half of the patients with ADHD (58%) had associated specific learning disorders. Furthermore, teachers tended to report executive function difficulties more frequently in male students. ConclusionsIn the study sample, the group of patients with ADHD exhibited cognitive performance within the normal range, although with lower scores compared to controls. Behavioural rating scales provide valuable information about functioning outside the clinic, but may yield biased results on account of the focus on externalising symptoms. The neuropsychological evaluation is a useful tool that can facilitate the diagnosis of ADHD and an effective response to the needs and characteristics of patients and families.

Cognitive and sleep evaluation of Myotonic dystrophy type I: A protocol for a case‐control study

AbstractBackgroundMyotonic dystrophy type 1 (DM1) is one of the most common inherited muscular dystrophies in adults. It is caused by CTG repeat expansions in the 3' untranslated region (UTR) of the DMPK gene on Chromosome 19. Apart from muscle, the disease can involve the eye, heart, brain and endocrine system. Cognitive and sleep disturbances are common but poorly recognized non‐motor manifestations of DM1.MethodWe plan to recruit 30 genetically proven DM1 patients from the prospective MRC‐funded International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) cohort. Neuromuscular phenotyping will be done by the same neuromuscular expert. The muscle strength will be assessed by the Medical Research Council scale and Muscular Impairment Rating Scale (MIRS). We will exclude patients with severe depression. An age and sex‐matched control group of 30 healthy participants will be included to evaluate patients’ cognitive profiles. A comprehensive neuropsychological evaluation (NPS) to assess multiple cognitive domains will be conducted on all patients. A prescheduled sleep history, Epworth Sleepiness Scale (ESS), Pittsburg sleep quality index (PSQI) and full‐night diagnostic polysomnography will be done in all patients.ResultThe outcomes include the NPS domains comparing cognitive impairment compared to controls and the severity and type of sleep apnea (apnea‐hypopnea index [AHI])ConclusionThe study will investigate the DM1 cognitive profile and its relationship with sleep disturbance using motor scales, neuropsychological assessment and polysomnography.

Association of Polygenic Risk Score of Alzheimer’s disease with A/T/N Biomarkers and Cognitive Decline

AbstractBackgroundPolygenic risk scores (PRS) quantify the combined effects of genetic variants to enable the prediction of an individual’s risk of developing the disease. Alzheimer’s disease (AD) is a complex disorder in which the relationship among PRS, neuropathological substrates, and related cognitive decline remain especially understudied in Asian populations. We investigated the associations of PRS with AD neuroimaging biomarkers and cognitive phenotypes in a Korean Cohort.MethodThe study included 501 older adults (264 cognitively normal [CN], 146 mild cognitive impairment [MCI], and 91 AD dementia) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). Comprehensive clinical and neuropsychological evaluations, as well as multi‐modal neuroimaging including 3T MRI and 11C‐PiB‐PET were administered. A subset of participants underwent 18F‐AV‐1451 PET (n = 167). Imaging phenotypes including beta‐amyloid (Aβ) positivity, global tau deposition, and adjusted hippocampal volume (HVa) were used for amyloid (A), tau (T), and neurodegeneration (N) biomarkers, respectively., which was imputed using the TOPMed reference panel. PRS was calculated using the summary statistics of a recent large‐scale GWAS study for AD by PRS‐CS. The Apolipoprotein E (APOE) region was excluded in the calculation. The associations between standardized PRS and imaging/cognitive phenotypes were examined using either multiple linear or logistic regression analysis with covariates (age and sex for neuroimaging biomarker phenotypes; age, sex and education for cognitive phenotypes).ResultPRS was significantly higher in the AD dementia group compared to the CN group. Higher PRS was associated with greater CDR‐sum‐of‐boxes (β[SE] = 0.233[0.083], t = 2.818, p = 0.005) and lower MMSE scores (β[SE] = ‐0.648[0.198], t = ‐3.271, p = 0.001). In terms of AD neuroimaging biomarkers (Figure 1), higher PRS was significantly associated with an increased likelihood of Aβ positivity (OR = 1.233, 95%CI = 1.024‐1.491), and lower HVa (β[SE] = ‐132.79[49.624], t = ‐2.676, p = 0.008), but not with global tau deposition (β[SE] = 0.075[0.048], t = 1.573, p = 0.118).ConclusionThese findings suggest that higher PRS predicts increased pathological Aβ deposition and accelerated neurodegeneration, as well as greater cognitive decline. Further investigation in larger and multiethnic samples are needed to determine generalizability to other ethnoracial populations.

Diagnostic of Novel Plasma Biomarkers in Controls, SCD and MCI Subjects

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia, and a challenging disease for the development of plasma biomarkers. Blood samples are the most easily collectable samples for medical diagnosis. This study evaluates the potential of plasma biomarkers in identifying early stages of AD.Method189 participants were recruited at the NYU Alzheimer Disease Research Center. This cohort includes n = 75 with normal cognition (NL), n = 77 with subjective cognitive decline (SCD), n = 37 with mild cognitive impairment (MCI). Comprehensive neuropsychological and magnetic resonance imaging evaluations were conducted for all patients. Plasma biomarkers assays (total tau [t‐tau], neurofilament light [NfL], glial fibrillary acid protein [GFAP], ubiquitin carboxyl‐terminal hydrolase L1 [UCH‐L1], Aβ1‐42, Aβ1‐40 and pTau181) were measured using the SIMOA SR‐X, a novel technology that employs highly sensitive immunoassays with a limit of detection (LOD) under 100 fg/ml.ResultThe levels of NfL, t‐Tau, GFAP and UCH‐L1 were measured using the Neurology 4‐plex A. NfL levels showed a significant difference between NL and SCD (one tailed t‐ test p = 0.0459). GFAP showed statistically significant differences between NL and MCI, (one tailed t‐test p = 0.0369). Aβ1‐42 showed a significant difference between SCD and MCI (one tailed t‐test p = 0.0493). pTau181 levels showed a significant difference between NL, SCD and NL, MCI (p = 0.0447 and p = 0.0439, respectively). The ratio of pTau181/Aβ1‐42 shows a significant difference between NL and MCI (one tailed t‐test p = 0.0187). Correlation of these biomarkers with brain imaging and cognitive measures is underway.ConclusionBiomarker levels of NfL, GFAP, Aβ1‐42, pTau181 and Ratio pTau181/Aβ1‐42 in plasma samples showed several significant differences between the three groups of subjects. Plasma biomarkers can be useful for the diagnosis of AD related pathology at early stages.

Proteome Analysis in Plasma and Brain Reveals a Novel Plasma Biomarker Linked to Antemortem Cognitive Impairment and Postmortem Neuropathological Traits for Alzheimer Disease

AbstractBackgroundIdentification of blood‐based biomarkers that are indicative of Alzheimer’s disease (AD) pathology may help with early detection.MethodsWe generated proteome data for ∼7,000 proteins in both antemortem plasma and postmortem brain tissue from 103 participants of the Boston University Alzheimer’s Disease Research Center. All participants completed comprehensive neuropsychological evaluations and dementia severity was measured by global cognitive dementia rating (CDR) scores. A pathological AD diagnosis was established using NIA Reagan criteria. We conducted association tests with dementia (i.e., CDR ≥1 for dementia, CDR &lt;1 for control) and autopsy‐confirmed AD status as binary outcomes. Plasma proteins significantly associated with clinical or pathological AD (P&lt;0.05) were tested for association with quantitative cognitive tests and AD‐related neuropathological traits in which outcomes were rank‐transformed after adjusting for sex and either age at last antemortem exam or death.ResultsOf the 103 brain donors, 43 were diagnosed with dementia and 55 had autopsy‐confirmed AD. Five proteins (ACES, AURKB, CBARP, G45IP, and MMP‐8) measured in plasma were significantly associated with both pathological AD and dementia, while 252 plasma proteins were associated with either diagnosis (P&lt;0.05). MMP‐8 was the only protein that was significantly associated in both plasma and brain with autopsy‐confirmed AD (Pplasma = 0.005, Pbrain = 0.001) and dementia (Pplasma = 0.01, Pbrain = 9×10−5). ACES and AURKB levels in plasma and brain were significantly associated with dementia (P&lt;0.05). Levels of these. Increased MMP‐8 level in plasma was associated with decreased animals (P = 0.03) and scores (P = 0.04), which both assess verbal fluency. Dementia and pathologically confirmed AD were associated with lower AURKB and elevated ACES levels in plasma. Decreased plasma ACES level was associated with executive function (TrailsB: P = 0.01) and language (Boston Naming Test: P = 0.02) impairment, and the reduced plasma AURKB level was associated with memory impairment (Logical Memory Immediate Recall score: P = 0.03).ConclusionMMP‐8, a neutrophil collagenase and member of the matrix metalloproteinase family, is a potential blood‐based biomarker for dementia and underlying AD pathology and is associated predominantly with impaired verbal fluency.

Subjective cognitive impairment and biomarkers of Alzheimer’s disease

AbstractBackgroundSubjective cognitive impairment (SCI) is common in older adults. It may represent the earliest clinical manifestation of cognitive decline and Alzheimer’s disease (AD).Objectives1) to evaluate associations between SCI and cerebrospinal fluid (CSF) biomarkers of AD; 2) to identify specific single questions or question combinations that are related to the presence of cerebral AD pathology; 3) to evaluate whether using SCI related scores or specific questions combined with other clinical features and biomarkers may improve prediction of cognitive decline.MethodWe conducted a longitudinal study in 164 non‐demented subjects participating on a biomarker study in a memory clinic setting, aged 53 to 88 years, with CDR scores of 0 (N = 84) and 0.5 (N = 80). SCI was assessed using the Cognitive Complaint Interview (CCI, Thomas‐Antérion et al., 2006), a validated 10 items questionnaire. Accordingly, SCI is defined as present when the subject answers “yes” to 3 or more items; and/or to item 5, and/or to items A, 4, 5, 7, 8. All participants underwent comprehensive neuropsychological evaluations and CSF biomarkers analysis. “Amyloid positivity" and “AD pathology” were defined according to the CSF Aβ1‐42 levels and pTau181/Aβ1‐42 ratio, respectively. Logistic regressions were used to address the associations of interest.ResultsParticipants with SCI had significantly lower Aβ1‐42 and higher Tau and pTau181 levels compared to those without SCI. SCI was associated with amyloid positivity while CCI total score and the question A (reporting changes in memory) were associated with both amyloid positivity and AD pathology in the whole cohort. When performing analysis separately in the CDR = 0 and CDR = 0.5 subgroups the associations remained significant in the CDR = 0.5 group. Only question 6 (difficulties in finding words) was associated with AD pathology in the CDR = 0 group. Results on the prediction of cognitive decline at follow‐up visits will be presented at the conference.ConclusionIn dementia‐free subjects from this memory clinic cohort SCI‐related scores and single questions indicate amyloid positivity and the presence of AD pathology depending on the absence/presence of mild cognitive impairment. Further studies are needed to evaluate the diagnostic and prognostic utility of cognitive complains in memory clinic patients.

INNV-30. DEVELOPMENT AND IMPLEMENTATION OF A NOVEL, BRIEF NEUROCOGNITIVE SCREENING AND REHABILITATION SERVICE IN A CLINICAL NEURO-ONCOLOGY SETTING

Abstract BACKGROUND Although neurocognitive dysfunction is common in patients with brain tumors, existing screening methods (e.g., Montreal Cognitive Assessment) lack sensitivity for detecting neurocognitive difficulties. Moreover, existing neurocognitive screens provide only modest clinical utility for characterizing individual neurocognitive strengths/weaknesses critical for treatment planning. METHODS Beginning in February 2023, the Alvord Brain Tumor Center at the University of Washington Medical Center (UWMC) implemented the Rehabilitation Neuropsychology Screening Service (RNSS). The RNSS is an internal outpatient service staffed by a rehabilitation neuropsychologist from the Department of Rehabilitation Medicine at UWMC. Neuro-oncologists and advanced practice providers placed referrals to the RNSS based on clinical need and cognitive symptoms. On average, 1-2 referrals per week were received. RESULTS Patients referred to the RNSS have included those with high- and low-grade gliomas with varying degrees of everyday functioning status (e.g., independence at home, goals to return to work/school) and neurocognitive symptoms. The goal of the RNSS is to explore inclusion and exclusion criteria that optimize patient experience and outcomes while maximizing outreach to patients in need of neurorehabilitation services. The RNSS includes brief, repeatable neuropsychological testing (90-minutes) and patient-reported outcomes (e.g., mood, quality of life). A separate feedback appointment is then held with patients to describe personal neurocognitive strengths/weaknesses and provide neurorehabilitation strategies or rehabilitation resources/referrals based on findings. In select cases, RNSS has served as a triage stage for stepped care towards referrals to a more comprehensive neuropsychological evaluation. CONCLUSION The development and implementation of this novel approach to neurocognitive screening and rehabilitation, including the rationale, workflow of patient care, and expected outcomes, is described. With additional quality assessment/improvement, the RNSS may serve as a model for integrating neurorehabilitation services into existing neuro-oncology clinics, and may be an additional guide for patients and families towards neurorehabilitation resources and education.

66 Neuropsychological Profile of ROHHAD Syndrome: A Case Study

Objective:Rapid Onset Obesity with Hypoventilation, Hypothalamic Dysfunction, Autonomic Dysregulation (ROHHAD) is a rare and often progressive syndrome with unknown etiology and only 100 cases reported to date. The syndrome is characterized by generally normal development followed by rapid onset of pain, muscle weakness, personality changes, and developmental regression. Associated chronic pain and fatigue result in difficulty concentrating, slow information processing, and executive function challenges. Only one study has examined the neuropsychological profile of pediatric patients with this syndrome.Participants and Methods:Our patient was a 10-year-old, right-handed male with a history of ROHHAD syndrome, focal epilepsy, mild neurocognitive disorder, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) who underwent two comprehensive neuropsychological evaluations at our medical center.Results:Findings across multiple evaluations showed solid verbal skills and difficulty processing visual-spatial and nonverbal information, as well as problems with attention, executive functioning, and adaptive skills, and psychosocial functioning consistent with his diagnoses of ADHD and ASD. He exhibited fine-and gross-motor challenges associated with hypotonia. Chronic fatigue contributed to his challenges with attention and information processing. These findings are generally consistent with previous research examining the neuropsychological profile associated with ROHHAD syndrome.Conclusions:Results from our case study highlight the complexity and challenges associated with ROHHAD syndrome. Consistent with available information, etiology of our patients’ neuropsychological weakness and functional decline is unclear. Yearly neuropsychological evaluations are recommended for these patients to update interventions based on their variable abilities. More research is needed to firmly establish the neuropsychological profile in youth of varying ages afflicted with this syndrome.