Impact of obese body mass index on inflammasome blood biomarkers and neurocognitive performance following traumatic brain injury with Glasgow coma scale 13 to 15

Article

作者: Kershaw, Erin E ; Eagle, Shawn R ; Henry, Rebecca J ; Sherry, Natalie ; McIntyre, Peyton ; Okonkwo, David O ; Puccio, Ava ; Basantani, Mahesh K

Activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a moderating factor between obesity and cognitive impairment in animals, but this has never been tested in humans following mild traumatic brain injury (mTBI). This is a retrospective cohort analysis of subjects enrolled at a single level 1 trauma center (n = 172). Participants completed Trail Making Test Part A and B (TMT-A and B) at six- and twelve-months, Blood samples were obtained within 24 h of mTBI and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, interleukin-18 (IL-18), and IL-1β were assayed. Obese participants (BMI = 30-34.9) were associated with higher IL-18 (p = 0.03) and IL-1β (p = 0.05) and severely obese participants (BMI > 35.0) were associated with higher IL-1β (p = 0.005) than healthy weight participants. IL-1β was associated with TMT-A at six- (p = 0.01) and twelve-months (p = 0.03) and TMT-B at twelve-months (p = 0.046). The interaction of severely obese BMI and IL-1β was associated with TMT-B at six- (p = 0.049) and twelve-months (p = 0.02). ASC (p = 0.03) and the interaction of ASC with severely obese BMI was associated with TMTB at six- (p = 0.02) and twelve-months (p = 0.02). Obesity may augment acute inflammasome response to mTBI and influence worse long-term cognitive outcomes up to one-year post-injury.

2024-09-01·Australasian Journal on Ageing

Effect of cognitive training on cognitive function in community‐dwelling older people with mild‐to‐moderate dementia: A single‐blind randomised controlled trial

Article

作者: Payne, Narelle ; Sturnieks, Daina L. ; Delbaere, Kim ; Kurrle, Susan E. ; Chantanachai, Thanwarat ; Savage, Roslyn ; Taylor, Morag E. ; Lord, Stephen R. ; Close, Jacqueline C. T.

AbstractObjectivesThe purpose of this assessor‐blinded, randomised controlled trial was to determine the effect of computerised cognitive training (CT) on executive function, processing speed and working memory in 61 people with mild‐to‐moderate dementia.MethodsThe primary outcomes were forward Digit Span and Trail Making Tests (TMT) at the completion of the 6‐month intervention. Secondary outcomes included cognitive and physical performance, rate of falls, participant and caregiver's quality of life and usability and adherence to the CT program. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12617000364370).ResultsIntervention group (n = 31) participants averaged 81 min of CT per week, and system usability scores were acceptable (participants: 68.8 ± 22.1; caregivers: 79.4 ± 23.5). There were no statistically significant differences in cognitive or physical performance outcomes between the intervention and control groups at 6‐ or 12‐months (between‐group differences [95% CI] for primary outcomes at 6‐months: Forward Digit Span −0.3 [−0.8, 0.3]; TMT‐A 2.7 s [−14.1, 19.5]; TMT‐B −17.1 s [−79.3, 45.2]). At the 12‐month follow‐up reassessment, the intervention group reported significantly more depressive symptoms and had lower caregiver‐rated participant quality of life and higher caregiver quality of life compared to control.ConclusionsThis study showed no benefit of the CT program on working memory, processing speed and executive function. Future studies are required to better understand how CT can be used to improve cognitive and physical functioning in older people with mild–moderate dementia.

2021-12-01·Progress in Neuro-Psychopharmacology and Biological Psychiatry2区 · 医学

Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes

2区 · 医学

Article

作者: Changchun Xie ; Amanda Smith ; Yongke Lu ; Chun Xu ; Alzheimer's Disease Neuroimaging Initiative ; Danqing Xiao ; Ubolrat Piamjariyakul ; R Osvaldo Navia ; Kesheng Wang

BACKGROUNDThe Trail Making Test (TMT) Part A (TMT-A) is a good measure of performance on cognitive processing speed. This study aimed to perform a genome-wide association study of TMT-A in Alzheimer's disease (AD).METHODSA total of 757 individuals with TMT-A phenotypes and 620,901 single nucleotide polymorphisms (SNPs) were extracted from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort. AD related cognitive phenotypes include TMT-A, TMT-B, Functional Activities Questionnaire (FAQ), Clinical Dementia Rating Sum of Boxes (CDR-SB), and Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS13). Multivariable linear regression analysis of TMT-A was conducted using PLINK software. The most TMT-A associated gene was tested with Color Trails Test 1 Form A (CTTA), a culturally fair analog of the TMT-A. Functional annotation of SNPs was performed using the RegulomeDB and Genotype-Tissue Expression (GTEx) databases.RESULTSThe best signal with TMT-A was rs1108010 (p = 4.34 × 10^-8) at 11p15.2 within INSC gene, which was also associated with TMT-B, FAQ, CDR-SB, and ADAS13 (p = 2.47 × 10^-4, 8.56 × 10^-3, 0.0127 and 0.0188, respectively). Furthermore, suggestive loci were identified such as FOXD2 and CLTA with TMT-A, GBP1/GBP3 with TMT-B, GRIK2 with FAQ, BAALC and CCDC146 with CDR-SB, BAALC and NKAIN2 with ADAS13. Additionally, the best SNP within INSC associated with CTTA was rs7931705 (p = 6.15 × 10^-5). Several SNPs had significant eQTLs using GTEx.CONCLUSIONSWe identified several genes/loci associated with TMT-A and AD related phenotypes. These findings offer the potential for new insights into the pathogenesis of cognitive function and Alzheimer's disease.

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