Background: Alzheimer’s disease (AD), which is characterized by progressive brain dysfunction and memory loss, is one of the most significant global health concerns for older adults. Neuroinflammation and increased oxidative stress contribute to the pathophysiology of AD, thereby presumably inducing tryptophan (TRP) degradation through the TRP catabolite (TRYCAT) pathway. Objective: To delineate the activity of the TRYCAT pathway along with levels of TRP and tryptophan catabolites (TRYCATs) in AD patients. Methods: We used PubMed, Google Scholar, Web of Science, and SciFinder during the month of January 2022 to gather the pertinent publications. We found 19 eligible articles which involved 738 patients and 665 healthy controls. Results: Our results revealed a significant difference (p = 0.008) in the kynurenine (KYN)/TRP ratio (standardized mean difference, SMD = 0.216, 95% confidence interval, CI: 0.057; 0.376), and a significant decrease in TRP in AD patients (SMD = –0.520, 95% CI: –0.738; –0.302, p < 0.0001). Moreover, we also found a significant increase in the central nervous system (CNS), brain, and cerebrospinal fluid kynurenic acid (KA)/KYN ratio but not in peripheral blood, as well as a significant decrease in plasma KA and xanthurenic acid in the CNS and blood. Conclusion: AD is characterized by TRP depletion but not by an overactivity of the TRYCAT pathway. IDO-induced production of neurotoxic TRYCATs is not a key factor in the pathophysiology of AD.

IntroductionThe purpose of this study was to (1) validate the Thai version of the Neuropsychiatric Inventory Questionnaire (NPI-Q) as a screening tool for behavioral and psychological symptoms of dementia (BPSD), and (2) examine the relationship between cognitive performance and BPSD in an elderly population with amnestic mild cognitive impairment (aMCI) and dementia of Alzheimer’s type (DAT).MethodsOne hundred and twenty participants, comprising 80 aMCI and 40 DAT patients, and their respective caregivers were included in the study. Participants completed the NPI-Q and the Neuropsychiatric Inventory (NPI) within 2 weeks of each other and cognitive performance was primarily assessed using the Montreal Cognitive Assessment (MoCA).ResultsThe Thai NPI-Q had good validity and reliability. Pure exploratory bifactor analysis revealed that a general factor and a single-group factor (with high loadings on delusions, hallucinations, apathy, and appetite) underpinned the NPI-Q domains. Significant negative correlations between the MoCA total score and the general and single-group NPI-Q scores were found in all subjects (aMCI + DAT combined) and DAT alone, but not in aMCI. Cluster analysis allocated subjects with BPSD (10% of aMCI and 50% of DAT participants) into a distinct “DAT + BPSD” class.ConclusionThe NPI-Q is an appropriate instrument for assessing BPSD and the total score is largely predicted by cognitive deficits. It is plausible that aMCI subjects with severe NPI-Q symptoms (10% of our sample) may have a poorer prognosis and constitute a subgroup of aMCI patients who will likely convert into probable dementia.

In older adults with amnestic Mild Cognitive Impairment (aMCI), the Cambridge Neuropsychological Test Automated Battery (CANTAB) probes indicated cognitive impairments most frequently in memory. This study aimed to investigate a) the cognitive features of aMCI using memory CANTAB tests and b) whether the clinical diagnosis of aMCI can be externally validated by these CANTAB measurements. We tested CANTAB tests that are specific to aMCI on 65 healthy controls and 66 people with aMCI who were diagnosed using Petersen`s criteria. These tests were spatial working memory (SWM), visual pattern recognition memory (PRM), delayed matching to sample (DSM), spatial span (SSP), and rapid visual information processing (RVP). The key aMCI features are impairments in PRM and DSM, whilst deficits in SSP and RVP are other, albeit somewhat less important features of aMCI. Nevertheless, neural network analyses including 10 CANTAB domains specific for MCI showed that only 70.8 percent of all subjects were properly identified with a sensitivity of 77.3%, specificity of 65.4% and an area under the ROC curve of 0.760. K-means cluster analysis using the same specific CANTAB test scores discovered 2 clusters with an adequate silhouette measure of cohesion and separation including a cluster with 36 subjects showing impairments in most neurocognitive tests. Deficits in spatial working, pattern recognition and visuospatial working memory as well as rapid visual information processing are key features of aMCI. Nevertheless, the clinical diagnosis of aMCI according to Petersen`s criteria is overinclusive because too many healthy controls are allocated to this group.