Neuropsychological Exam Research Articles

Prediction of Alzheimer's disease progression within 6 years using speech: A novel approach leveraging language models.

Identification of individuals with mild cognitive impairment (MCI) who are at risk of developing Alzheimer's disease (AD) is crucial for early intervention and selection of clinical trials. We applied natural language processing techniques along with machine learning methods to develop a method for automated prediction of progression to AD within 6 years using speech. The study design was evaluated on the neuropsychological test interviews of n=166 participants from the Framingham Heart Study, comprising 90 progressive MCI and 76 stable MCI cases. Our best models, which used features generated from speech data, as well as age, sex, and education level, achieved an accuracy of 78.5% and a sensitivity of 81.1% to predict MCI-to-AD progression within 6 years. The proposed method offers a fully automated procedure, providing an opportunity to develop an inexpensive, broadly accessible, and easy-to-administer screening tool for MCI-to-AD progression prediction, facilitating development of remote assessment. Voice recordings from neuropsychological exams coupled with basic demographics can lead to strong predictive models of progression to dementia from mild cognitive impairment. The study leveraged AI methods for speech recognition and processed the resulting text using language models. The developed AI-powered pipeline can lead to fully automated assessment that could enable remote and cost-effective screening and prognosis for Alzehimer's disease.

Comparison of combined intravenous and inhalation anesthesia and total intravenous anesthesia in laparoscopic surgery and the identification of predictive factors influencing the delayed recovery of neurocognitive function.

Compare the anesthesia effects of combined intravenous and inhalation anesthesia (CIVIA) and total intravenous anesthesia (TIVA) in laparoscopic surgery. Furthermore, our objective is to examine the elements that contribute to the delay in postoperative recovery of neurocognitive function and anticipate the manifestation of delayed recovery by analyzing serum cytokines. The CIVIA group and the TIVA group both consisted of 130 patients who were scheduled to have elective major abdominal surgery through laparoscopy. The criteria taken into account by the observational and record-keeping study were the patients' ages, sexes, body masses, heights, and the presence or absence of any preexisting problems. Both groups also had their anesthetic depth, duration, and per-unit-of-time muscle relaxant and analgesic dosages recorded. Finally, the length of each patient's stay in the hospital as well as their overall length of stay were tracked. By using the Mini-Mental State Examination (MMSE) to measure cognitive function, we assessed the mental states of the subjects. Additionally, we wanted to identify any biomarkers that could be linked to postoperative cognitive decline or delays in neurocognitive recovery. A total of 51 participants from the CIVIA group and 53 participants from the TIVA group satisfactorily completed the necessary neuropsychological exam for identifying delayed neurocognitive recovery at the study's completion. In the initial data of the two groups, no significant discrepancies were found (p > 0.05). The CIVIA group exhibited noteworthy reductions in the quantity of administered analgesics and muscle relaxants per unit of time in comparison to the TIVA group (p < 0.05). In addition to this, the duration from the sevoflurane tank being closed to the extubation period demonstrated a significant reduction in the CIVIA group compared to the TIVA group (p < 0.05). Moreover, no statistically notable distinction was observed in terms of postoperative hospitalization duration and overall hospitalization duration among both groups (p > 0.05). According to the study, both the CIVIA group and the TIVA group had a total of 7 (13.72%) and 17 (32.07%) individuals, respectively, who met the criteria for neurocognitive delayed recovery (Odds Ratio: 0.336; 95% CI: 0.134-0.864; p = 0.026). According to the research findings, it is indicated that there is a possibility for an increased presence of IL-6 in the bloodstream within 60 min following the incision made on the skin. This occurrence subsequently leads to the prolonged restoration of neurocognitive capabilities. The CIVIA technique outperforms the TIVA method in terms of overall assessment in the setting of laparoscopic surgery. It's also important to remember that an increased blood IL-6 level during laparoscopy may operate as a separate risk factor for a delay in the restoration of neurocognitive function.

Abstract P270: Higher Long-Term Fasting Glucose Variability From Childhood is Associated With Poorer Cognitive Function in Midlife: The Bogalusa Heart Study

Background: Elevated fasting blood glucose(FBG) levels have been associated with poorer cognitive function. High FBG variability has also been associated with accelerated cognitive decline in late life. However, the impact of long term FBG variability from childhood on midlife cognitive function (CF) remains understudied. Hypothesis: We hypothesized that there would be an association of higher long-term FBG variability from childhood with poorer midlife CF measures. Aim: We aimed to identify the influence of higher long term FBG variability on midlife CF. Methods: We studied 1,005 midlife Bogalusa Heart Study participants (age at baseline: mean 9.4 years +/- SD 3.5 years; age at neuropsychological(NP) exam: mean 47.9 years+/- SD 5.2 years; 60.4% women(607 of 1005); 33.5 % Black(337 of 1005)) with ≥3 FBG measurements across follow up. Participants having type 2 diabetes mellitus(T2DM) were excluded. T2DM was defined as FBG ≥126 mg/dL or taking diabetes medication. Long-term visit-to visit FBG variability was measured as deviation from age predicted values (DEV) and residual SD (RSD). Using ≥3 FBG measurements, DEV and RSD were obtained from individual growth curves created by fitting random-effects models stratified by race and sex. Participants’ midlife CF was first measured with 10 NP tests, then were classified into 3 distinct NP profiles (optimal, average, and mixed-low) using cluster analysis. Multinomial logistic regression models were used to analyze the associations between long-term FBG variability parameters and NP profiles, adjusting for education status and mean of FBG measures from childhood to midlife . DEV and RSD were standardized to z-scores by race and sex before regression analysis. Tests for interaction according to race and sex were conducted. Results: After adjusting for the mean FBG level and education status, for a 1 SD increase in DEV, the odds of having a mixed-low CF increased by 57.3% (95% CI 1.244, 1.990) and the odds of an average CF increased by 36.9% (95% CI 1.144, 1.640) respectively, compared to optimal CF. After adjusting for the mean FBG level and education status, for a 1 SD increase in RSD, the odds of having a mixed-low CF increased by 56% (95% CI 1.232, 1.974) and the odds of an average CF increased by 37.7% (95% CI 1.147, 1.653), respectively, compared to optimal CF. No significant interactions between long-term FBG variability parameters and race and sex were found. Conclusions: Higher long-term FBG variability was associated with poorer midlife CF. Further studies are needed to identify the role of long-term FBG variability in the association of cardiometabolic risk factors and midlife CF.

Altered patterns of brain activity during a fMRI memory task in cognitively normal adults carrying the APOE ε4 allele

AbstractBackgroundThe ε4 allele of the Apolipoprotein E gene (APOE) is a well‐established risk factor for Alzheimer’s disease (AD), ε4 carriers showing earlier onset and more severe memory impairment than non‐carriers. Neuroimaging evidence suggests that APOEε4 may modulate neural activity in AD since early stages. The purpose of this study was to determine whether APOEε4 influences brain activity in the memory circuit in older cognitively unimpaired individuals.MethodThirty cognitively unimpaired participants (n = 10 APOEε4 heterozygous carriers, age = 65± 5 years, 50% females, MMSE score = 29±1; n = 20 APOEε4 non‐carriers, age = 68±5 years, 35% females, MMSE score = 30±1) were recruited and underwent multidomain (i.e., memory, visuospatial abilities, language, attention) neuropsychological exams and functional MRI scan during an associative memory task, which consisted of two phases: (i) encoding of face‐name associations; (ii) recognition of the name associated to each face. Image preprocessing and voxel‐wise comparisons were conducted using the Statistical Parametric Mapping (SPM, v12). Clusters were considered significant at an uncorrected threshold of p&lt;0.001.ResultParticipants were comparable for demographic and cognitive features (p&gt;0.10) and performed similarly on the in‐scanner face‐name association memory task (p&gt;0.10). Compared to ε4 non‐carriers, carriers showed (i) greater activation during the encoding task in the left temporo‐occipital cortex/fusiform gyrus, (ii) greater activation during the recognition task in the middle temporal gyrus/temporo‐occipital cortex bilaterally and in the right cerebellum, and (iii) lower activation during the recognition task in the medial supplementary motor area.ConclusionThese preliminary results confirm that the APOE ε4 allele is associated with a different pattern of brain functional activity during an associative memory task in cognitively unimpaired older. Given the similar cognitive performance between groups, higher activation in temporo‐occipital regions might reflect a compensatory process in regions vulnerable to AD pathology.

Altered patterns of brain activity during a fMRI memory task in cognitively normal adults carrying the APOE ε4 allele

AbstractBackgroundThe e4 allele of the Apolipoprotein E gene (APOE) is a well‐established risk factor for Alzheimer’s disease (AD), e4 carriers showing earlier onset and more severe memory impairment than non‐carriers. Neuroimaging evidence suggests that APOEe4 may modulate neural activity in AD since early stages. The purpose of this study was to determine whether APOEe4 influences brain activity in the memory circuit in older cognitively unimpaired individuals.MethodThirty cognitively unimpaired participants (n = 10 APOEe4 heterozygous carriers, age = 65± 5 years, 50% females, MMSE score = 29±1; n = 20 APOEe4 non‐carriers, age = 68±5 years, 35% females, MMSE score = 30±1) were recruited and underwent multidomain (i.e., memory, visuospatial abilities, language, attention) neuropsychological exams and functional MRI scan during an associative memory task, which consisted of two phases: (i) encoding of face‐name associations; (ii) recognition of the name associated to each face. Image preprocessing and voxel‐wise comparisons were conducted using the Statistical Parametric Mapping (SPM, v12). Clusters were considered significant at an uncorrected threshold of p&lt;0.001.ResultParticipants were comparable for demographic and cognitive features (p&gt;0.10) and performed similarly on the in‐scanner face‐name association memory task (p&gt;0.10). Compared to e4 non‐carriers, carriers showed (i) greater activation during the encoding task in the left temporo‐occipital cortex/fusiform gyrus, (ii) greater activation during the recognition task in the middle temporal gyrus/temporo‐occipital cortex bilaterally and in the right cerebellum, and (iii) lower activation during the recognition task in the medial supplementary motor area.ConclusionThese preliminary results confirm that the APOE e4 allele is associated with a different pattern of brain functional activity during an associative memory task in cognitively unimpaired older. Given the similar cognitive performance between groups, higher activation in temporo‐occipital regions might reflect a compensatory process in regions vulnerable to AD pathology.

Impairment of the locus coeruleus‐transentorhinal cortex pathway in persons at risk of Alzheimer’s disease.

AbstractBackgroundRecent studies reported microstructural alterations in the locus coeruleus ‐ transentorhinal cortex (LC‐TEC) pathway in patients with Alzheimer’s disease (AD) but data in subjects at risk of AD (i.e., cognitively intact APOEε4 carriers) are missing. In this study, we apply in‐vivo diffusion weighted images (DWI) to study the effect of APOEε4 on the LC‐TEC pathway in cognitively unimpaired subjects.MethodForty‐five participants (14 APOEε4 carriers: age = 68±7 years, 45% females, MMSE score = 29±0.9; 31 non‐carriers: age = 68±6 years, 57% females, MMSE score = 30±0.6) underwent multimodal 3T MRI and multidomain neuropsychological exams. DWI were corrected for distortions with topup and eddy tools (part of FMRIB’s Software Library – FSL). Microstructural measures as fractional anisotropy (FA), mean (MD), axial (AxD), and radial (RD) diffusivities maps were estimated using the FMRIB’s Diffusion Toolbox (part of FSL) after the exclusion of cerebrospinal fluid voxels. Microstructural integrity of LC‐TEC was assessed using a thresholded probabilistic atlas non‐linearly warped on native maps with FNIRT (part of FSL). A Bonferroni multivariate generalized linear model, corrected for age and sex, was conducted to compare the diffusivity indexes between APOEε4 carriers and non‐carriers. Association with memory functioning (immediate and delayed recall) was also tested using Spearman’s rank correlations test.ResultAPOEε4 carriers and non‐carriers were comparable for cognitive performance (p&gt;.246). Compared to non‐carriers, APOEε4 carriers showed lower FA (p = 0.048) and higher RD (p = 0.036) in the left LC‐TEC. In APOEε4 carriers, left RD negatively correlated with both immediate (rho = ‐0.808, p&lt;0.001) and delayed (rho = ‐0.673, p = 0.025) memory recall.ConclusionMicrostructural alterations of the LC‐TEC pathway are detectable in subjects at‐risk for AD and correlate with lower memory performance. These preliminary results support the view that LC‐TEC impairment may play a role in AD pathophysiology since its early stages.

Impairment of the locus coeruleus‐transentorhinal cortex pathway in persons at risk of Alzheimer’s disease

AbstractBackgroundRecent studies reported microstructural alterations in the locus coeruleus ‐ transentorhinal cortex (LC‐TEC) pathway in patients with Alzheimer’s disease (AD) but data in subjects at risk of AD (i.e., cognitively intact APOEe4 carriers) are missing. In this study, we apply in‐vivo diffusion weighted images (DWI) to study the effect of APOEe4 on the LC‐TEC pathway in cognitively unimpaired subjects.MethodForty‐five participants (14 APOEe4 carriers: age = 68±7 years, 45% females, MMSE score = 29±0.9; 31 non‐carriers: age = 68±6 years, 57% females, MMSE score = 30±0.6) underwent multimodal 3T MRI and multidomain neuropsychological exams. DWI were corrected for distortions with topup and eddy tools (part of FMRIB’s Software Library – FSL). Microstructural measures as fractional anisotropy (FA), mean (MD), axial (AxD), and radial (RD) diffusivities maps were estimated using the FMRIB’s Diffusion Toolbox (part of FSL) after the exclusion of cerebrospinal fluid voxels. Microstructural integrity of LC‐TEC was assessed using a thresholded probabilistic atlas non‐linearly warped on native maps with FNIRT (part of FSL). A Bonferroni multivariate generalized linear model, corrected for age and sex, was conducted to compare the diffusivity indexes between APOEe4 carriers and non‐carriers. Association with memory functioning (immediate and delayed recall) was also tested using Spearman’s rank correlations test.ResultAPOEe4 carriers and non‐carriers were comparable for cognitive performance (p&gt;.246). Compared to non‐carriers, APOEe4 carriers showed lower FA (p = 0.048) and higher RD (p = 0.036) in the left LC‐TEC. In APOEe4 carriers, left RD negatively correlated with both immediate (rho = ‐0.808, p&lt;0.001) and delayed (rho = ‐0.673, p = 0.025) memory recall.ConclusionMicrostructural alterations of the LC‐TEC pathway are detectable in subjects at‐risk for AD and correlate with lower memory performance. These preliminary results support the view that LC‐TEC impairment may play a role in AD pathophysiology since its early stages.

40 APOE x BDNF Genetic Interaction is Associated with Poorer Cognitive Outcomes in Veterans with Histories of mTBI

Objective:Many Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans have sustained a mild traumatic brain injury (mTBI) during their military service and a substantial “miserable minority” frequently report significant cognitive complaints long after injury. Although existing studies have shown associations between genetic factors (e.g., apolipoprotein E [APOE] and brain-derived neurotrophic factor [BDNF]) and cognitive performance in this vulnerable population, the TBI-genetics literature has generally been varied and inconsistent. Although past findings suggest that individuals who possess APOE £4 and BDNF Met alleles have worse cognitive outcomes after mTBI, this has not been consistently reported. Additionally, the influence of any gene-by-gene interactions on cognition has not been sufficiently explored and therefore remains a critical area of interest. Thus, we examined relationships between APOE and BDNF genotypes on neuropsychological function in a well-characterized sample of younger Veterans with mTBI histories.Participants and Methods:Participants included Veterans with a history of mTBI who adequately completed performance validity testing. In total, 78 Veterans (84.6% male; age: M=32.95, SD=7.00; race/ethnicity: 51.3% White, 28.2% Hispanic/Latino, and 20.5% Another Race/Ethnicity) completed a structured clinical interview to collect detailed information on TBI history and underwent a comprehensive neuropsychological exam. A buccal swab was also collected to determine APOE and BDNF allele status for each participant. Three cognitive composite scores were computed reflecting memory (8 items), attention/processing speed (7 items), and executive functioning (10 items). Two-way analyses of covariance (ANCOVAs) adjusting for age, sex, and race/ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning (ε4+/Met-: n=12, ε4+/Met+: n=8, £4-/Met-: n=35, and ε4-/Met+: n=23).Results:ANCOVAs revealed no significant main effects for APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE x BDNF genotype interaction for all three cognitive composites (memory: p=.026, np2=.068; attention/processing speed: p=.045, np2=.055; and executive functioning: p=.031, np2=.064). Specifically, the interaction was such that Veterans in the ε4+/Met+ group demonstrated the poorest cognitive functioning relative to all other allele group combinations (ε4+/Met-, ε4-/Met+, ε4-/Met-).Conclusions:The results of this preliminary study demonstrate that, compared to the other genetic subgroups in the TBI sample, Veterans with APOE £4 and BDNF Met alleles demonstrated the poorest cognitive functioning across several domains known to be negatively affected in the context of head injury (i.e., memory, attention/processing speed, and executive functioning). These findings are the first to show an APOE x BDNF interaction in Veterans with histories of mTBI. Furtherresearch is necessary to replicate and extend this study in larger samples. Moreover, future work should incorporate neuroimaging variables to better interrogate structural and functional correlates of these observed genetic polymorphism associations in Veterans with mTBI histories.

Piecing it together: atrophy profiles of hippocampal subfields relate to cognitive impairment along the Alzheimer's disease spectrum.

People with Alzheimer's disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls. Participants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes. Our results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory. These findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum.

Hearts and Minds: Emotion Recognition and Mentalizing in Parkinson's Disease and Progressive Supranuclear Palsy.

There are scarce data comparing Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP) in social cognition (SC). We aimed to compare patients with PSP and PD in SC. We included three groups: PD (n = 18), PSP (n = 20) and controls (n = 23). Participants underwent neuropsychological exams, including the mini-version of the Social and Emotional Assessment, which is composed of the facial emotion recognition test (FERT) and the modified faux-pas (mFP) test, which assesses Theory of Mind (ToM). Patients with PD scored lower than controls in the FERT, but not in the mFP test. Patients with PSP performed worse than controls in both the mFP and FERT. PD and PSP groups did not differ in the FERT, but PSP performed worse than PD in the mFP test. The mFP test distinguished PSP from PD with 89% accuracy. The assessment of ToM may contribute to the differentiation between PD and PSP.

Association of acoustic perturbation measures with dementia status: A Framingham Heart Study

AbstractBackgroundDiagnosis of dementia due to Alzheimer’s disease (AD) is a resource‐intensive process, often requiring clinical assessments and neuroimaging which may fall beyond the reach of patients in remote settings. Given the challenges of traditional dementia work‐up, identification of disease‐relevant signatures from low‐cost modalities has attracted interest as a means to improve disease detection. Here, we describe a machine learning strategy to associate acoustic perturbations in voice with dementia status using digital recordings of neuropsychological exams administered in the Framingham Heart Study (FHS).MethodWe used 118 voice recordings from 79 participants to extract jitter, shimmer, and haronics‐to‐nosie ratio (HNR) from the ComParE 2016 dataset. Each of these acoustic perturbation measures are commonly used in the clinical context to characterize pathological voice. For each voice transcript, these features were computed and and fed as input to a one‐dimensional convolutional neural network to predict dementia status. The data was randomly split in the ratio of 1:1 (at the participant‐level), where 50% of the cases were used for training and the remaining for testing. This process was repeated 10 times and the average model performance was reported. For each model run, the neural network was trained for 500 epochs without early stopping and the model obtained after the final epoch was used for testing.ResultThe mean (±std) age of the participants included in the study was 82.6±8.3 years, and 21 of them were ApoE positive. The mean (±std) area under the receiver operating characteristic curve and the mean (±std) area under the precision‐recall curve of the model classifying participants with dementia from those with normal cognition was 0.673±0.043 and 0.791±0.052, respectively (Fig. 1). Also, the mean accuracy (±std) was 0.615±0.025, the mean precision (±std) was 0.714±0.121, and the mean sensitivity/recall (±std) was 0.721±0.179.ConclusionOur study presents a proof‐of‐principle that deep learning on acoustic perturbation measures can predict dementia status. Further studies with additional participants and an expanded set of acoustic, speech and linguistic features are needed to evaluate the full potential of machine learning to derive disease‐relevant signatures from audio data, and potentially expand the reach of early detection and intervention efforts.

Visit-to-Visit Blood Pressure Variability and Cognitive Decline in Apolipoprotein ɛ4 Carriers versus Apolipoprotein ɛ3 Homozygotes.

Blood pressure variability (BPV) is associated with cognitive decline and Alzheimer's disease (AD), but relationships with AD risk gene apolipoprotein (APOE) ɛ4 remain understudied. Examined the longitudinal relationship between BPV and cognitive change in APOE ɛ4 carriers and APOE ɛ3 homozygotes. 1,194 Alzheimer's Disease Neuroimaging Initiative participants (554 APOE ɛ4 carriers) underwent 3-4 blood pressure measurements between study baseline and 12-month follow-up. Visit-to-visit BPV was calculated as variability independent of mean over these 12 months. Participants subsequently underwent ≥1 neuropsychological exam at 12-month follow-up or later (up to 156 months later). Composite scores for the domains of memory, language, executive function, and visuospatial abilities were determined. Linear mixed models examined the 3-way interaction of BPV×APOE ɛ4 carrier status x time predicting change in composite scores. Higher systolic BPV predicted greater decline in memory (+1 SD increase of BPV: β= -0.001, p < 0.001) and language (β= -0.002, p < 0.0001) among APOE ɛ4 carriers, but not APOE ɛ3 homozygotes (memory: +1 SD increase of BPV: β= 0.0001, p = 0.57; language: β= 0.0001, p = 0.72). Systolic BPV was not significantly associated with change in executive function or visuospatial abilities in APOE ɛ4 carriers (ps = 0.08-0.16) or APOE ɛ3 homozygotes (ps = 0.48-0.12). Cognitive decline associated with high BPV may be specifically accelerated among APOE ɛ4 carriers.

How to combine the use of intraoperative magnetic resonance imaging (MRI) and awake craniotomy for microsurgical resection of hemorrhagic cavernous malformation in eloquent area: a case report

BackgroundCavernous malformations are clusters of abnormal and hyalinized capillaries without interfering brain tissue. Here, we present a cavernous malformation operated under awake conditions, due to location, in an eloquent area and using intraoperative magnetic resonance imaging due to patient’s movement upon the awake phase.Case presentationWe present the pre-, per-, and postoperative course of an inferior parietal cavernous malformation, located in eloquent area, in a 27-year-old right-handed Caucasian male, presenting with intralesional hemorrhage and epilepsy. Preoperative diffusion tensor imaging has shown the cavernous malformation at the interface between the arcuate fasciculus and the inferior fronto-occipital fasciculus. We describe the microsurgical approach, combining preoperative diffusion tensor imaging, neuronavigation, awake microsurgical resection, and intraoperative magnetic resonance imaging.ConclusionComplete microsurgical en bloc resection has been performed and is feasible even in eloquent locations. Intraoperative magnetic resonance imaging was considered an important adjunct, particularly used in this case as the patient moved during the “awake" phase of the surgery and thus neuronavigation was not accurate anymore. Postoperative course was marked by a unique, generalized seizure without any adverse event. Immediate and 3 months postoperative magnetic resonance imaging confirmed the absence of any residue. Pre- and postoperative neuropsychological exams were unremarkable.

Association of Area Deprivation Index and hypertension, diabetes, dyslipidemia, and Obesity: A Cross-Sectional Study of the HABS-HD Cohort.

Objective: This study aims to investigate the association between neighborhood deprivation and the prevalence of major cardiovascular disease (CVD) risk factors (hypertension, diabetes, dyslipidemia, and obesity) in a Mexican American (MA) population compared to NonHispanic Whites (NHW). Method: A cross-sectional analysis was conducted to include 1,867 subjects (971 MA and 896 NHW). Participants underwent a clinical interview, neuropsychological exam battery, functional examination, MRI of the head, amyloid PET scan, and blood draw for clinical and biomarker analysis. We use the Area Deprivation Index (ADI) Model to assign an ADI score to participants based on their neighborhoods. Descriptive, Cochran-Armitage test for trend, and odds ratio statistical analysis were applied. Results: Our results suggest that NHW had higher odds of having HTN, DM, and obesity in the most deprived neighborhoods, while MA showed no increased odds. The study also found that neighborhood deprivation contributed to diabetes in both MA and NHW and was associated with obesity in NHW. Conclusions: These findings highlighted the importance of addressing both individual and societal factors in efforts to reduce cardiovascular risk. Future research should explore the relationship between socio-economic status and cardiovascular risk in more detail to inform the development of targeted interventions.

An AI‐based approach to detect cognitive impairment from digital voice recordings of neuropsychological assessments

AbstractBackgroundReliable cognitive impairment screening tools that are easy to administer and minimally time consuming are greatly needed. Given the high sensitivity of neuropsychological (NP) exams in detection of cognitive decline, we seek to develop an automated screening tool to detect dementia and mild cognitive impairment (MCI) based on digital voice recordings of NP assessments. This could enable wide‐spread screening for dementia and accelerate preventative efforts.MethodWe used natural language processing methods to create a screening tool that identifies different stages of dementia based on automated transcription of digital voice recordings. The transcribed sentences were classified into 8 main sub‐tests including memory assessment, naming and language skill, verbal fluency, general questions, etc. Using the idea of transfer learning, we encoded the participants' sentences into quantitative data. This data and the participants’ demographic variables such as age, sex, Apoe gene, and education were employed to train and test three binary classification tasks, (I) Normal cognition versus Dementia, (II) Normal/MCI versus Dementia, and (III) Normal versus MCI.ResultWe evaluated the performance of the classification tasks using the digital voice recordings of NP assessments, collected from the Framingham Heart Study, containing 410 cognitively intact subjects, 387 MCI, and 287 subjects with dementia. The average Area Under the Curve (AUC) on the held‐out test data reached 92.6%, 88.0%, and 74.4% for differentiating Normal from Dementia, Normal or MCI from Dementia, and Normal from MCI, respectively. Looking at the importance of the sub‐tests in differentiating MCI from Normal, we note that general questions can be more useful for assessment of MCI, whereas verbal fluency would not be as useful in this task.ConclusionThe proposed approach offers a fully automated identification of MCI and dementia based on a recorded NP test, providing an opportunity to develop a remote screening tool that could be easily adapted to any language.

Higher Dietary Inflammatory Index scores are not associated with cognitive decline in the Framingham Heart Study

AbstractBackgroundNutritional factors can abet or protect against systemic chronic inflammation, which plays an important role in the development and progression of dementia. We evaluated whether higher (i.e. pro‐inflammatory) Dietary Inflammatory Index(DII) scores were associated with accelerated cognitive decline in the community‐based Offspring Framingham Heart Study(FHS).Method889 older adults (mean age 59 years [standard deviation (SD)], 8;58.3% women]) completed validated 126‐item Food Frequency Questionnaires(FFQ), administered at FHS examination cycle 7 (1998‐2001) and examination cycle 5 (1991‐1995) and/or 6 (1995‐1998). We created a DII score (based on the published method by Shivappa et al. 2014); a cumulative DII score was calculated by averaging across a maximum of three FFQs. Cognitive testing was completed at examination cycles 7, 8 (2005‐2008) and 9 (2011‐2014). Exam 7 was considered as study baseline and participants were followed over a mean time of 13.4 years (SD 1.3). We excluded participants with prevalent dementia or stroke at baseline and those with no cognitive testing follow‐up data. We examined associations between the cumulative DII score and cognitive test scores over time using linear mixed models adjusting for age, age‐squared, sex, education, time from exam 7 to neuropsychological exam 7, and time (model1) and additionally for apolipoprotein e4, body mass index, total energy intake, total cholesterol: high‐density lipoprotein ratio, physical activity, smoking and anti‐cholesterol medication (model2).ResultHigher DII scores were significantly associated with accelerated decline in performance on the Trail Making Test B minus A(TMT‐B minus A) (processing speed and executive function), following adjustment for model 1 covariates (β±SE, ‐0.001± 0.0004,p = 0.03). but the association failed to reach significance in Model 2 (‐0.001±0.0003,p = 0.08). We observed no relationship between higher DII scores and other cognitive domains. Stratified analyses showed that higher DII scores were associated with accelerated decline in TMT‐B minus A scores among apolipoprotein e4 carriers (Model 2:‐0.002±0.001,p = 0.047) but not among non‐carriers (Model 2:‐0.0004±0.0004,p = 0.33).ConclusionHigher DII scores were not associated with cognitive decline. To date, such studies have been very limited, most studies that found a relationship, were cross‐sectional and have used less sensitive testing. Future studies are encouraged to examine whether our findings can be replicated.

Sex differences in APOE effects on cognition are domain‐specific

AbstractBackgroundTwo‐thirds of Alzheimer’s disease (AD) patients are women and there are well‐established sex differences in the association between APOE and cognitive impairment in AD. However, it is not clear whether sex‐specific cognitive consequences of APOE emerge across all cognitive domains or in a domain‐specific manner.MethodData were obtained from 38,386 participants in four longitudinal studies of aging and AD. The average age of participants at baseline was 75±8 years (10% AD, 42% male, 12% African American [AA], 12% APOE‐ε2 carriers, and 36% APOE‐ε4 carriers). Based on detailed neuropsychological exams, harmonized composite scores for memory, executive function, and language were generated using latent variable modeling. Linear regression assessed APOE*sex interactions on each baseline cognitive domain score. Mixed‐effects regression models assessed sex interactions with APOE on cognitive trajectories, including fixed and random effects for both the intercept and the slope (years from baseline). All models adjusted for age at baseline, sex, and race/ethnicity. Exploratory analyses of the potential effect of race/ethnicity were also performed using an APOE*sex*race interaction term in the model.ResultAs expected, APOE‐ε4 was associated with worse cognitive performance, and APOE‐ε2 was associated with better performance in all domains, both at baseline and longitudinally (p&lt;0.001). At baseline, we observed a significant sex*APOE‐ε4 interaction on memory (β=‐0.06, p&lt;0.001) and significant sex*APOE‐ε2 interaction on memory (β=0.05, p=0.03). In both cases, the association between APOE and memory was significantly stronger in females compared to males. Notably, despite the large sample size, no interactions were observed in the two other cognitive domains or in the longitudinal analysis. Additionally, we observed a significant interaction between sex*APOE‐ε2*race on baseline memory (β=‐0.19, p=0.02), whereby the APOE‐ε2*sex interaction was significant in non‐Hispanic whites (β=0.06, p&lt;0.01) but not in AA (β=‐0.11, p=0.10).ConclusionWe provide new evidence that the sex difference in APOE in cognition is most pronounced in relation to memory performance and is particularly driven by differences in baseline performance rather than trajectories of performance over time. Future work will examine intersections with clinical diagnosis to better differentiate sex differences in APOE associations in the context of normal aging and neurodegenerative disease.

Assessment of Cognitive Assistive Technologies in Elderly Patients with Dementia Post-COVID-19 Infection: A Research Proposal

Introduction: SARS-CoV-2 infection is thought to be implicated in an increased risk for various neurodegenerative diseases given its role in neuroinflammation. As a result, cognitive assistive technologies to monitor the risk of neurodegenerative diseases in those with prior COVID-19 infection and the regular implementation of practices designed to promote synaptic plasticity may decrease the risk of dementia in susceptible populations. It is hypothesized that incorporating frequent use of a mobile application designed to improve memory five times per week in the daily routines of patients aged 65+ who have survived a COVID-19 infection may decrease the prevalence of subsequent dementia. Methods: The goal of this application would be to (i) deliver interventions related to long-term potentiation, and (ii) centralizing patient health data in a singular domain to improve ease of access for caregivers and medical staff. This may be investigated through a two-pronged randomized controlled trial aimed to compare neural and cognitive functioning through repeat neuropsychological exams, magnetic resonance imaging, and electroencephalogram tests over a 6-year timeframe between no-intervention and intervention groups while collecting caregiver and healthcare worker data regarding its efficacy in improving quality of life. Results: It is expected that patients consistently using cognitive assistive technologies in long-term care facilities will experience lower incidence of cognitive decline compared to the control group due to improved maintenance of mental health and the learning of new skills. In addition, with the use of technology, patients may experience increased autonomy and independence, improving their quality of life while simultaneously providing relief to their families and caregivers. Discussion: Some further considerations may include the degree of technological proficiency of the patients during the development process to ensure that patients reap the maximum benefits. Factors including rapid development and testing, funding, and strong technology support systems must be taken into consideration to ensure a seamless transition to increased reliance on technology in post-COVID-19 patients with dementia. Conclusion: Strong evidence indicates technology-based interventions can be used to by dementia patients and their caretakers overcome physical and environmental challenges normally and during future pandemic waves.

Neuropsychological Decline Stratifies Dementia Risk in Cognitively Unimpaired and Impaired Older Adults.

ObjectiveValidation and widespread use of markers indicating decline in serial neuropsychological exams has remained elusive despite potential value in prognostic and treatment decision-making. This study aimed to operationalize neuropsychological decline, termed “neuropsychological (NP) decline,” in older adults followed over 12 months in order to aid in the stratification of dementia risk along the cognitively unimpaired-to-mild cognitive impairment (MCI) spectrum.MethodsA prospective cohort study utilized 6,794 older adults from the National Alzheimer’s Coordinating Center (NACC) database with a baseline diagnosis of normal cognition, impaired without MCI or with MCI. Operationalization of NP decline over 12-month follow-up used regression-based norms developed in a robustly normal reference sample. The extent to which each participant’s 12-month follow-up score deviated from norm-referenced expectations was quantified and standardized to an NP decline z-score. Cox regression evaluated whether the NP decline metric predicted future dementia.ResultsParticipant’s NP decline scores predicted future all-cause dementia in the total sample, χ2 = 110.71, hazard ratio (HR) = 1.989, p < 0.001, and in the subset diagnosed with normal cognition, χ2 = 40.84, HR = 2.006, p < 0.001, impaired without MCI diagnosis, χ2 = 14.89, HR = 2.465, p < 0.001, and impaired with MCI diagnosis, χ2 = 55.78, HR = 1.916, p < 0.001.ConclusionOperationalizing NP decline over 12 months with a regression-based norming method allows for further stratification of dementia risk along the cognitively unimpaired-to-MCI spectrum. The use of NP decline as an adjunctive marker of risk beyond standard cognitive diagnostic practices may aid in prognosis and clinical decision-making.

Increased regional white matter hyperintensity volume in objectively-defined subtle cognitive decline and mild cognitive impairment

White matter hyperintensities (WMH), a marker of small vessel cerebrovascular disease, increase risk of developing mild cognitive impairment (MCI) and Alzheimer's disease (AD). Less is known about the extent and pattern of WMH in pre-MCI stages, such as among those with objectively-defined subtle cognitive decline (Obj-SCD). Five hundred and fifty-nine Alzheimer's Disease Neuroimaging Initiative participants (170 cognitively unimpaired [CU]; 83 Obj-SCD; 306 MCI) free of clinical dementia or stroke completed neuropsychological testing and MRI exams. ANCOVA models compared cognitive groups on regional WMH adjusting for age, sex, and apolipoprotein E (APOE) ɛ4 frequency. Compared with the CU group, those with Obj-SCD had greater temporal, occipital, and frontal WMH whereas those with MCI had higher WMH volume across all regions (p’s < 0.01). No differences in WMH volume were observed between the Obj-SCD and MCI groups (p’s > 0.05). Findings add to growing evidence of associations between Obj-SCD and imaging biomarkers, providing support for utility of these criteria to capture subtle cognitive changes that are biologically based.