Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored.

Background: Individuals with Down syndrome (DS) are at high risk for dementia, specifically Alzheimer's disease. However, many measures regularly used for the detection of dementia in the general population are not suitable for individuals with DS due in part to floor effects. Some measures, including the Severe Impairment Battery (SIB), Brief Praxis Test (BPT) and Dementia Scale for People with Learning Disabilities (DLD), have been used in clinical trials and other research with this population. Validity research is limited, particularly regarding the use of such tools for detection of prodromal dementia in the DS population. The current project presents baseline cross‐sectional SIB, BPT and DLD performance in order to characterise their predictive utility in discriminating normal cognition, possible dementia and probable dementia in adult DS.Method: Baseline SIB, BPT and DLD performances from 100 individuals (no dementia = 68, possible dementia = 16 & probable dementia = 16) were examined from a longitudinal cohort of aging individuals with DS. Receiver operating characteristic curves investigated the accuracy of these measures in relation to consensus dementia diagnoses, diagnoses which demonstrated high percent agreement with the examining neurologist's independent diagnostic impression.Results: The SIB and BPT exhibited fair discrimination ability for differentiating no/possible versus probable dementia [area under the curve (AUC) = 0.61 and 0.66, respectively]. The DLD exhibited good discrimination ability for differentiating no versus possible/probable dementia (AUC = 0.75) and further demonstrated better performance of the DLD Cognitive subscale compared with the DLD Social subscale (AUC = 0.77 and 0.67, respectively).Conclusions: Results suggest that the SIB, BPT and DLD are able to reasonably discriminate consensus dementia diagnoses in individuals with DS, supporting their continued use in the clinical assessment of dementia in DS. The general performance of these measures suggests that further work in the area of test development is needed to improve on the AUCs for dementia status discrimination in this unique population. At present, however, the current findings suggest that the DLD may be the best option for reliable identification of prodromal dementia in this population, reinforcing the importance of including informant behaviour ratings in assessment of cognition for adults with DS.

Aquaporin-4 (AQP4) is implicated in Alzheimer's disease (AD) pathology through its role in astrocytic function, cerebrovascular integrity, and beta-amyloid (Aβ) clearance. Impaired Aβ clearance in AD is linked to changes in AQP4 distribution; however, the role of AQP4 in AD associated with Down Syndrome (DS) is poorly understood. This study investigates AQP4 protein levels, its relationship with Aβ deposition, and distribution patterns in DS. Using human post-mortem brain sections from the frontal and occipital cortex, we analyzed AQP4 and Aβ levels in samples from neurotypical controls, DS, DS with AD (DSAD), and late onset AD (LOAD). Protein levels and distribution were assessed using immunohistochemistry and immunofluorescence with quantitative imaging tools. AQP4 protein levels were higher with age in both neurotypical control and DS groups, but not in the LOAD group. AQP4 and Aβ were positively correlated with age in the frontal cortex of all groups. AQP4 and Aβ were positively correlated with each other after adjusting for age in the frontal cortex in both the control and DS groups which was not observed in the occipital cortex. In the frontal cortex of both DS and DSAD, AQP4 was more frequently distributed to the soma and proximal branches and less to astrocytic endfeet compared to the control group, consistent with previous reports of impaired glymphatic clearance and perivascular regulation. These findings support a relationship between altered AQP4 protein levels and distribution, Aβ accumulation, and region-specific vulnerability in DS and AD.

Emergent Large Vessel Occlusion (ELVO) strokes are ischemic vascular events for which novel biomarkers and therapies are needed. The purpose of this study is to investigate the role of Body Mass Index (BMI) on protein expression and signaling at the time of ELVO intervention. Additionally, we highlight the protein adenosine deaminase (ADA), which is a deaminating enzyme that degrades adenosine, which has been shown to be neuroprotective in ischemia. We investigate the relationship between ADA and BMI, stroke outcomes, and associated proteomic networks which might aid in personalizing prognosis and future treatment of ELVO stroke. The Blood And Clot Thrombectomy And Collaboration (BACTRAC) study is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) and registry from stroke patients undergoing mechanical thrombectomy (MT). N ​= ​61 human carotid plasma samples were analyzed for inflammatory and cardiometabolic protein expression by Olink Proteomics. Statistical analyses used t-tests, linear, logistic, and robust regressions, to assess the relationship between BMI, proteomic expression, and stroke-related outcomes. The 61 subjects studied were broken into three categories: normal weight (BMI 18.5–24.9) which contained 19 subjects, overweight (BMI 25–30) which contained 25 subjects, and obese (BMI ≥30) which contained 17 subjects. Normal BMI group was a significantly older population (mean 76 years) when compared to overweight (mean 66 years) and obese (mean 61 years) with significance of p ​= ​0.041 and p ​= ​0.005, respectively. When compared to normal weight and overweight categories, the obese category had significantly higher levels of adenosine deaminase (ADA) expression (p ​= ​0.01 and p ​= ​0.039, respectively). Elevated levels of ADA were found to have a significant positive correlation with both infarct volume and edema volume (p ​= ​0.013 and p ​= ​0.041, respectively), and were associated with a more severe stroke (NIHSS on discharge) and greater stroke related disability (mRS on discharge) with significance of p ​= ​0.053 and p ​= ​0.032, respectively. When examined according to BMI, subjects undergoing MT for ELVO demonstrate significant differences in the expression of certain plasma proteins, including ADA. Levels of ADA were found to be significantly higher in the obese population when compared to normal or overweight groups. Increased levels of ADA in the obese group were predictive of increased infarct volume, edema volume, and worse NIHSS scores and mRS at discharge. These data provide novel biomarker candidates as well as treatment targets while increasing the personalization of stroke prognosis and treatment.

Primary care integration of Down syndrome (DS)-specific dementia screening is strongly advised. The current study employed principal components analysis (PCA) and classification and regression tree (CART) analyses to identify an abbreviated battery for dementia classification. Scale- and subscale-level scores from 141 participants (no dementia n = 68; probable Alzheimer’s disease n = 73), for the Severe Impairment Battery (SIB), Dementia Scale for People with Learning Disabilities (DLD), and Vineland Adaptive Behavior Scales—Second Edition (Vineland-II) were analyzed. Two principle components (PC1, PC2) were identified with the odds of a probable dementia diagnosis increasing 2.54 times per PC1 unit increase and by 3.73 times per PC2 unit increase. CART analysis identified that the DLD sum of cognitive scores (SCS < 35 raw) and Vineland-II community subdomain (<36 raw) scores best classified dementia. No significant difference in the PCA versus CART area under the curve (AUC) was noted (D(65.196) = −0.57683; p = 0.57; PCA AUC = 0.87; CART AUC = 0.91). The PCA sensitivity was 80% and specificity was 70%; CART was 100% and specificity was 81%. These results support an abbreviated dementia screening battery to identify at-risk individuals with DS in primary care settings to guide specialized diagnostic referral.

Objective: To determine whether primitive reflexes serve as an indicator of dementia in adults with Down syndrome (DS), we collected neurologic examination data, cognitive and behavioral assessments, and clinical consensus diagnoses of dementia from 92 adults with DS. Methods: In a cross-sectional, observational study of a regional cohort, chi-square and Fisher’s exact tests examined individual reflexes across diagnostic group (No, Possible, or Probable Dementia). In 64 participants with all 8 reflexes assessed, the number of primitive reflexes was assessed as a predictor of diagnosis using age-controlled multinomial logistic regression and of performance on clinical assessments (Brief Praxis Test [BPT], Severe Impairment Battery [SIB], and the Dementia Questionnaire for People with Learning Disabilities [DLD] using age-adjusted linear regression. Results: Primitive palmomental, grasp, snout, and suck reflexes were more frequent in individuals with probable dementia, but all participants showed at least one primitive reflex. Multiple primitive reflexes in combination served as a better indicator of dementia, with each additional abnormal reflex tripling probability of Probable Dementia group membership controlling for age. Abnormal reflex count was not associated with direct assessment of cognition and praxis (SIB and BPT) but associated with informant ratings of cognitive and behavioral functioning (DLD). Conclusions: The presence of multiple reflexes serves as an indicator of dementia status in DS as a supplement to direct assessment of cognition and praxis. The reflex examination may serve as a tool in the multimethod evaluation for dementia in DS, as it appears unaffected by intellectual disability and language mastery.