Development of a Nomogram-Based Tool to Predict Neurocognitive Impairment Among HIV-positive Charter Participants

Background: Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) persists in people living with HIV (PLWH). Studies have generated inconsistent results regarding etiological factors for NCI in PLWH. Furthermore, a user-friendly and readily available predictive tool is desirable in clinical practice to screen PLWH for NCI. Objective: This study aimed to identify factors associated with NCI using a large and diverse sample of PLWH and build a nomogram based on demographic, clinical, and behavioral variables. Methods: We performed Bayesian network analysis using a supervised learning technique with the Markov Blanket (MB) algorithm. Logistic regression was also conducted to obtain the adjusted regression coefficients to construct the nomogram. Results: Among 1,307 participants, 21.6% were neurocognitively impaired. During the MB analysis, age provided the highest amount of mutual information (0.0333). Logistic regression also showed that old age (>50 vs. ≤50 years) had the strongest association (OR=2.77, 95% CI=1.99-3.85) with NCI. The highest possible points on the nomogram were 626, translated to a nomogram-predicted probability of NCI to be approximately 0.95. The receiver operating characteristic (ROC) curve's concordance index was 0.75, and the nomogram's calibration plot exhibited an excellent agreement between observed and predicted probabilities. Conclusion: The nomogram used variables that can be easily measured in clinical settings and, thus, easy to implement within a clinic or web-interface platform. The nomogram may help clinicians screen for patients with a high probability of having NCI and thus needing a comprehensive neurocognitive assessment for early diagnosis and appropriate management.

Heterogeneity and Factorial Structure in Alzheimer’s Disease: A Cognitive Perspective

Background: Alzheimer’s disease (AD) patients show heterogeneous cognitive profiles which suggest the existence of cognitive subgroups. A deeper comprehension of this heterogeneity could contribute to move toward a precision medicine perspective. Objective: In this study, we aimed 1) to investigate AD cognitive heterogeneity as a product of the combination of within- (factors) and between-patients (sub-phenotypes) components, and 2) to promote its assessment in clinical practice by defining a small set of critical tests for this purpose. Methods: We performed factor mixture analysis (FMA) on neurocognitive assessment results of N = 230 patients with a clinical diagnosis of AD. This technique allowed to investigate the structure of cognitive heterogeneity in this sample and to characterize the core features of cognitive sub-phenotypes. Subsequently, we performed a tests selection based on logistic regression to highlight the best tests to detect AD patients in our sample. Finally, the accuracy of the same tests in the discrimination of sub-phenotypes was evaluated. Results: FMA revealed a structure characterized by five latent factors and four groups, which were identifiable by means of a few cognitive tests and were mainly characterized by memory deficits with visuospatial difficulties (“Visuospatial AD”), typical AD cognitive pattern (“Typical AD”), less impaired memory (“Mild AD”), and language/praxis deficits with relatively spared memory (“Nonamnestic AD”). Conclusion: The structure of cognitive heterogeneity in our sample of AD patients, as studied by FMA, could be summarized by four sub-phenotypes with distinct cognitive characteristics easily identifiable in clinical practice. Clinical implications under the precision medicine framework are discussed.

Neurocognitive outcomes of HIV-associated tuberculous meningitis

Background: The toll of tuberculous meningitis (TBM) in both mortality and disability is considerable, but advancements in rehabilitation have the potential to improve the functional abilities and the quality of survivors’ lives. However, the typical phenotype of neurocognitive impairment in TBM survivors remains unstudied in HIV-predominant populations in sub-Saharan Africa. Methods: We tested 36 survivors of TBM in Uganda with a comprehensive battery of neurocognitive assessments at 8 and 24 weeks after diagnosis, and compared results to a representative cohort of HIV-uninfected Ugandans. Results: While participants had a broad range of impairments at eight weeks, there was marked improvement by 24 weeks, when a phenotype of impairment including deficits in motor functioning, verbal learning and memory, processing speed, and executive function emerged. These deficits were present despite good clinician-rated functional status. The majority (23/27, 85%) had evidence of moderate to severe depression at week 8, and at week 24 (18/24, 75%). Conclusion: These findings highlight the need for more comprehensive neurocognitive assessment in the survivors of TBM, and further investment in and study of rehabilitation, including management of depression, to improve long-term outcomes in this population.

Assessment Practice of Patient-Centered Outcomes in Surgical Neuro-Oncology: Survey-Based Recommendations for Clinical Routine

The psycho-oncological burden related to the diagnosis of an intracranial tumor is often accompanied by neurocognitive deficits and changes in character, overall affecting health-related quality of life (HRQoL) and activities of daily living. Regular administration of adequate screening tools is crucial to ensure a timely detection of needs for support and/or specific interventions. Although efforts have been made to assure the quality of neuro-oncological care, clinical assessment practice of patient-reported outcomes (PROs) remains overall heterogeneous, calling for a concise recommendation tailored to neuro-oncological patients. Therefore, this survey, promoted by the German Society of Neurosurgery, was conducted to evaluate the status quo of health care resources and PRO/neurocognition assessment practices throughout departments of surgical neuro-oncology in Germany. 72/127 (57%) of registered departments participated in the study, including 83% of all university hospital units. A second aim was to shed light on the impact of quality assurance strategies (i.e., department certification as part of an integrative neuro-oncology cancer center; CNOC) on the assessment practice, controlled for interacting structural factors, i.e., university hospital status (UH) and caseload. Despite an overall good to excellent availability of relevant health care structures (psycho-oncologist: 90%, palliative care unit: 97%, neuropsychology: 75%), a small majority of departments practice patient-centered screenings (psycho-oncological burden: 64%, HRQoL: 76%, neurocognition: 58%), however, much less frequently outside the framework of clinical trials. In this context, CNOC affiliation, representing a specific health care quality assurance process, was associated with significantly stronger PRO assessment practices regarding psycho-oncological burden, independent of UH status (common odds ratio=5.0, p=0.03). Nevertheless, PRO/neurocognitive assessment practice was not consistent even across CNOC. The overall most commonly used PRO/neurocognitive assessment tools were the Distress Thermometer (for psycho-oncological burden; 64%), the EORTC QLQ-C30 combined with the EORTC QLQ-BN20 (for HRQoL; 52%) and the Mini-Mental Status Test (for neurocognition; 67%), followed by the Montreal Cognitive Assessment (MoCA; 33%). Accordingly, for routine clinical screening, the authors recommend the Distress Thermometer and the EORTC QLQ-C30 and QLQ-BN20, complemented by the MoCA as a comparatively sensitive yet basic neurocognitive test. This recommendation is intended to encourage more regular, adequate, and standardized routine assessments in neuro-oncological practice.

Frequencies and Neuropsychological Characteristics of Errors in the Clock Drawing Test

Background: Few studies have investigated associations between types of clock drawing test (CDT) errors and cognitive impairment. Objective: To explore associations of qualitative errors in the CDT with comprehensive neurocognitive assessment scores and clinical diagnosis. Methods: Outpatients at a memory clinic were enrolled. Frequencies of errors determined by Cahn’s method were explored according to cognitive status (cognitively normal [CN] (n = 279), mild cognitive impairment [MCI] (n = 321), and Alzheimer’s disease [AD]) (n = 575). Neuropsychological assessment scores were compared between participants with and without errors. Results: Stimulus-bound response (SB) was relatively rare (6.8%) in the CN group but was markedly more common in the MCI (23.4%) and AD (33.2%) groups. Conceptual deficit (CD) was found in more than 20%of CN individuals, as well as about 50%of AD patients. Planning deficit (PD) frequencies were relatively similar among the groups. SB in both of CN and MCI individuals, and CD in both of CN and MCI individuals were associated with lower scores in several neuropsychological assessments. Meanwhile, PD was not associated with lower assessment scores in any of CN, MCI, or AD individuals. Conclusion: The frequencies of SB and CD increased from CN, MCI, to AD but showed somewhat different patterns. Both SB and CD were associated with lower cognition in all three cognitive stages.

The association between depressive symptoms and neurocognitive impairment in people with well-treated HIV in Switzerland

Background: Depression may contribute to neurocognitive impairment (NCI) in people with HIV (PWH). Attributing NCI to depression rather than to HIV is complicated as depression may be both a causal factor and an effect of NCI. This study aimed to determine the association between depressive symptoms and NCI among PWH with well-controlled infection. Methods: The Neurocognitive Assessment in the Metabolic and Ageing Cohort study is an ongoing, prospective, longitudinal study of PWH aged ≥45 years old nested within the Swiss HIV Cohort Study. Neurocognitive Assessment in the Metabolic and Ageing Cohort study participants underwent neurocognitive assessment and grading of depressive symptoms using the Centre for Epidemiological Studies Depression Scale. Neurocognitive impairment categories were defined using Frascati criteria. Participants with NCI related to neurological or psychiatric confounders other than depression were excluded. The cross-sectional association between the Centre for Epidemiological Studies Depression score and neurocognitive impairment was examined taking Centre for Epidemiological Studies Depression score as a continuous variable and then as a binary variable using two score thresholds, 16 and 27. Results: Excluding 79 participants with confounding factors, 902 participants were studied: 81% were men; 96% had plasma viral loads <50 copies/ml; 35% had neurocognitive impairment; 28% had Centre for Epidemiological Studies Depression scores ≥16. Higher Centre for Epidemiological Studies Depression scores were associated with female sex ( p = 0.0003), non-Caucasian origin ( p = 0.011) and current/past intravenous drug use ( p = 0.002). Whilst neurocognitive impairment was associated with higher Centre for Epidemiological Studies Depression scores, the Centre for Epidemiological Studies Depression score was a poor predictor of having neurocognitive impairment (area under the ROC curve 0.604). Applying a Centre for Epidemiological Studies Depression score threshold of 16 predicted the presence of neurocognitive impairment with a sensitivity of 38.3% (specificity 77.2%), increasing the threshold to 27 lowered sensitivity to 15.4% (specificity 93.6%). Conclusion: In this large cohort of PWH in Switzerland, we did not observe a Centre for Epidemiological Studies Depression score threshold that was sensitive in predicting neurocognitive impairment. As neurocognitive impairment was however associated with higher Centre for Epidemiological Studies Depression scores, the data support the screening for and treatment of depression among PWH diagnosed with neurocognitive impairment.

Neurocognitive Assessment Tools for Military Personnel With Mild Traumatic Brain Injury: Scoping Literature Review

Background Mild traumatic brain injury (mTBI) occurs at a higher frequency among military personnel than among civilians. A common symptom of mTBIs is cognitive dysfunction. Health care professionals use neuropsychological assessments as part of a multidisciplinary and best practice approach for mTBI management. Such assessments support clinical diagnosis, symptom management, rehabilitation, and return-to-duty planning. Military health care organizations currently use computerized neurocognitive assessment tools (NCATs). NCATs and more traditional neuropsychological assessments present unique challenges in both clinical and military settings. Many research gaps remain regarding psychometric properties, usability, acceptance, feasibility, effectiveness, sensitivity, and utility of both types of assessments in military environments. Objective The aims of this study were to explore evidence regarding the use of NCATs among military personnel who have sustained mTBIs; evaluate the psychometric properties of the most commonly tested NCATs for this population; and synthesize the data to explore the range and extent of NCATs among this population, clinical recommendations for use, and knowledge gaps requiring future research. Methods Studies were identified using MEDLINE, Embase, American Psychological Association PsycINFO, CINAHL Plus with Full Text, Psych Article, Scopus, and Military & Government Collection. Data were analyzed using descriptive analysis, thematic analysis, and the Randolph Criteria. Narrative synthesis and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews) guided the reporting of findings. The psychometric properties of NCATs were evaluated with specific criteria and summarized. Results Of the 104 papers, 33 met the inclusion criteria for this scoping review. Thematic analysis and NCAT psychometrics were reported and summarized. Conclusions When considering the psychometric properties of the most commonly used NCATs in military populations, these assessments have yet to demonstrate adequate validity, reliability, sensitivity, and clinical utility among military personnel with mTBIs. Additional research is needed to further validate NCATs within military populations, especially for those living outside of the United States and individuals experiencing other conditions known to adversely affect cognitive processing. Knowledge gaps remain, warranting further study of psychometric properties and the utility of baseline and normative testing for NCATs.

Neuropsychological Impact of Cancer and Cancer Treatments

Survivors of primary central nervous system (CNS) cancers and non-CNS cancers often report cognitive deficits, thought to result from surgery, radiation, chemotherapy, and the presence of cancer itself, and which significantly impact quality of life in survivorship. To develop the most effective methods of remediation and rehabilitation for cognitive dysfunction in a growing population of cancer survivors, it is necessary to understand the disease- and treatment-related factors that contribute to cancer-associated cognitive dysfunction, the strengths and limitations of current methods of neurocognitive assessment, the relationship between self-reported cognitive difficulties and objective measures of neuropsychological function, and the treatment and management options available to those suffering from cognitive impairment following treatment. The current chapter reviews the etiology, types of neurocognitive assessment, and treatment and management methods, and includes suggestions for future research to better understand the complex nature of cancer-associated cognitive dysfunction.