Post-traumatic amnesia: a scoping review & content analysis of behavioral disturbances.

OBJECTIVE: The aim of this scoping review was to identify behavioral disturbances exhibited by patients in post-traumatic amnesia (PTA). While behavioral disturbances are common in PTA, research into their presentation and standardized measures for their assessment are limited. DESIGN: The study protocol was registered with PROSPERO (CRD42021268275). A scoping review of databases was performed according to pre-determined criteria on 29 July 2021 and updated on 13 July 2022. A conventional content analysis was used to examine and categorize behavioral disturbances. RESULTS: Thirty papers met the inclusion criteria, of which 27 reported observations and/or scores obtained on behavioral scales, and 3 on clinician interviews and surveys. None focused exclusively on children. Agitation was the most frequently assessed behavior, and Agitated Behavior Scale was the most used instrument. Content analysis, however, bore eight broad behavioral categories: disinhibition, agitation, aggression, lability, lethargy/low mood, perceptual disturbances/psychotic symptoms, personality change and sleep disturbances. CONCLUSION: Our study revealed that while standardized assessments of behavior of patients in PTA are often limited to agitation, clinical descriptions include a range of behavioral disturbances. Our study highlights a significant gap in the systematic assessment of a wide range of behavioral disturbances observed in PTA.

Clinical Significance of the Plasma Biomarker Panels in Amyloid-Negative and Tau PET-Positive Amnestic Patients: Comparisons with Alzheimer's Disease and Unimpaired Cognitive Controls.

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP (n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aß42/Aß40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aß42/Aß40 (rho = -0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized ß = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.

Prolonged duration of post-traumatic amnesia: A sensitive classification for predicting cognitive outcomes in children recovering from traumatic brain injury.

OBJECTIVE: A paucity of data exists regarding the duration of post-traumatic amnesia (PTA) as a predictor of cognitive functioning among children after traumatic brain injury (TBI). The study aimed to assess the relationship between PTA duration and areas of neurocognitive function among the pediatric population in the sub-acute phase of recovery and rehabilitation. METHODS: Data were collected from medical files on 103 children aged 5.5-16.5 hospitalized at a pediatric rehabilitation department with a diagnosis of moderate-severe TBI (msTBI) between the years 2004-2019. The Children Orientation and Amnesia Test was used to evaluate PTA duration. Measures of high-order cognitive abilities of attention and executive function were collected using the Test of Everyday Attention-Child version (TEA-Ch). RESULTS: Three PTA duration groups were assembled out of a cluster analysis: "Long PTA" (M = 21 days), "Very Long PTA" (M = 47 days), and "Extremely Long PTA" (M = 94 days). Analyses revealed that the "Long PTA" group preformed significantly better than the "Very Long PTA" and "Extremely Long PTA" groups on all TEA-Ch measures, that is, Selective Attention, Attentional Control Switching, and Sustained Attention. CONCLUSIONS: This study is the first to demonstrate that PTA duration is a useful predictor of high-order cognitive functions among children with msTBI in the sub-acute phase of recovery and rehabilitation. The findings emphasize the importance of using a more sensitive classification of prolonged PTA durations to improve outcome prediction and allocation of resources to those who can benefit most after severe brain injuries.

Mild Cognitive Impairment Subtype Performance in Comparison to Healthy Older Controls on the NIH Toolbox and Cogstate.

BACKGROUND: Early detection is necessary for the treatment of dementia. Computerized testing has become more widely used in clinical trials; however, it is unclear how sensitive these measures are to early signs of neurodegeneration. We investigated the use of the NIH Toolbox-Cognition (NIHTB-CB) and Cogstate-Brief computerized neuropsychological batteries in the identification of mild cognitive impairment (MCI) versus healthy older adults [healthy control (HC)] and amnestic (aMCI) versus nonamnestic MCI (naMCI). Exploratory analyses include investigating potential racial differences. METHODS: Two hundred six older adults were diagnosed as aMCI (n = 58), naMCI (n = 15), or cognitively healthy (HC; n = 133). RESULTS: The NIH Toolbox-CB subtests of Flanker, Picture Sequence Memory, and Picture Vocabulary significantly differentiated MCI from HC. Further, subtests from both computerized batteries differentiated patients with aMCI from those with naMCI. Although the main effect of race differences was noted on tests and in diagnostic groups was significant, there were no significant race-by-test interactions. CONCLUSIONS: Computer-based subtests vary in their ability to help distinguish MCI subtypes, though these tests provide less expensive and easier-to-administer clinical screeners to help identify patients early who may qualify for more comprehensive evaluations. Further work is needed, however, to refine computerized tests to achieve better precision in distinguishing impairment subtypes.

Factor Structure of the Agitated Behavior Scale in Traumatic Brain Injury During Posttraumatic Amnesia.

OBJECTIVE: To investigate the factor structure of the Agitated Behavior Scale (ABS) in patients with traumatic brain injury (TBI) in posttraumatic amnesia (PTA). SETTING: Inpatient TBI rehabilitation ward in Victoria, Australia. PARTICIPANTS: A total of 364 patients aged 16 to 92 years meeting diagnostic criteria for TBI and PTA admitted between September 2013 and October 2020. DESIGN: Retrospective cohort study utilizing electronic medical record data. MAIN MEASURES: The ABS and the Westmead Post-Traumatic Amnesia Scale (WPTAS). RESULTS: Exploratory factor analysis uncovered 2 moderately correlated underlying factors (0.52), labeled Restlessness and Aggression/Lability. Two items failed to demonstrate sufficiently large loadings on either factor. Both factors demonstrated adequate reliability (Cronbach α = 0.87 and 0.81 for Restlessness and Aggression/Lability, respectively). Linear regression indicated that higher WPTAS scores were associated with lower levels of Restlessness (ß = -.14, P < .001), supporting construct validity. Conversely, WPTAS scores were not significantly associated with Aggression/Lability (ß = -.12, P = .08). Subgroup analysis indicated that a history of mood disorder was associated with greater severity of Aggression/Lability (P = .02). Confirmatory factor analysis indicated superior fit of the identified 2-factor solution when compared with previously explored 1-, 2-, 3-, and 4-factor structures. CONCLUSION: This study suggests that the latent structure of the ABS is best explained by a single construct of agitation with 2 discrete facets reflecting Restlessness and Aggression/Lability. These subscales may be used in clinical practice to evaluate the severity of different aspects of agitated behavior, inform treatment decisions, and judge the efficacy of interventions over time. Further research is required to explain low factor loadings demonstrated by 2 items.

Ruling out feigned crime-related amnesia? A response to Acklin (2022).

In a recent paper, Acklin discussed a case of possible amnesia for a murder in terms of neurobiology, psychoanalysis, and personality assessment. Acklin accepted the defendant's claim of amnesia for the crime as genuine. The considerable literature that takes a skeptical view of crime-related amnesia was not cited, and the possibility of feigning or malingering was "ruled out" with a single sentence that does not withstand scrutiny. A review of the literature on feigned amnesia suggests that it may not be possible to rule out malingering even if the best available tools are used: There has been minimal investigation of most validity tests and estimates of base rates of feigned amnesia for a crime vary widely and make estimates of Negative Predictor Power highly unreliable. Although one cannot know from the information presented if Acklin's defendant legitimately experienced amnesia, feigning could not be ruled out using an interview and the test data cited by Acklin. I call for a moratorium on publication of further articles on crime specific amnesia that do not conscientiously examine other potential explanations and do not use current best practices for assessing negative response bias.

Sexual symptoms in post-traumatic stress disorder following childhood sexual abuse: a network analysis.

BACKGROUND: Even though recent research indicates that sexual symptoms are highly prevalent in post-traumatic stress disorder following childhood sexual abuse and cause severe distress, current treatments neither address them nor are they effective in reducing them. This might be due to a lack of understanding of sexual symptoms' specific role in the often complex and comorbid psychopathology of post-traumatic stress disorder following childhood abuse. METHODS: Post-traumatic, dissociative, depressive, and sexual symptoms were assessed in 445 inpatients with post-traumatic stress disorder following childhood sexual abuse. Comorbidity structure was analyzed using a partial correlation network with regularization. RESULTS: A total of 360 patients (81%) reported difficulties engaging in sexual activities and 102 patients (23%) reported to suffer from their sexual preferences. Difficulties engaging in sexual activities were linked to depressive and hyperarousal symptoms, whereas sexual preferences causing distress were linked to anger and dissociation. Dissociative amnesia, visual intrusions, and physical reactions to trauma reminders were of central importance for the network. Dissociative amnesia, depressed mood, lack of energy, and difficulties engaging in sexual activities were identified as bridge symptoms. Local clustering analysis indicated the non-redundancy of sexual symptoms. CONCLUSIONS: Sexual symptoms are highly prevalent in survivors of childhood sexual abuse with post-traumatic stress disorder. Further research is needed regarding the link of difficulties engaging in sexual activities, depression, and post-traumatic stress disorder, as well as regarding the association of dissociation and sexual preferences causing distress. Sexual symptoms require consideration in the treatment of post-traumatic stress disorder following childhood sexual abuse.

Cross-cultural adaptation, translation, and validation of a Spanish version of the Westmead Post-traumatic Amnesia Scale for use following a traumatic brain injury.

Health professionals need linguistically and culturally correct tools with proven validity to effectively assess people in their native language. This study aimed to translate and validate the Westmead Post-traumatic Amnesia Scale (WPTAS) into a Spanish version to measure the progression and duration of post-traumatic amnesia (PTA) in Spanish-speaking populations. Seven native Spanish and English translators, 11 therapists and 15 people with a traumatic brain injury (TBI) and nine people with non-traumatic acquired brain injury participated in the forward-backward translation method to adapt the WPTAS. Participants with a TBI in PTA (n = 20), out of PTA (n = 21), and controls without cognitive impairment (n = 21) participated in the validation test phase by completing the WPTAS, Selective Reminding Test, Short Portable Metal Status Questionnaire, Digit Span, and Agitated Behaviour Scale. The translated version of the WPTAS produced consistent responses and appropriate errors (2%) among all pre-test participants. Results from the validation phase showed that participants in PTA scored significantly lower in all tests (p < .05) when compared with those out of PTA and controls. The Spanish version of the WPTAS created and tested in this study is culturally and linguistically appropriate as well as valid for use with Spanish speakers.

Acute-onset amnesia: transient global amnesia and other causes.

Acute-onset amnesia is a dramatic neurological presentation that can cause considerable concern to both patient and clinician. The patient typically presents with an inability not only to retain new memories but also to access previously acquired memories, suggesting disturbance of hippocampal function. Transient global amnesia (TGA) is the most common cause of acute-onset amnesia, and is characterised by a profound anterograde and retrograde amnesia that typically lasts for up to 24 hours. Although TGA has a strikingly stereotypical presentation, it can be challenging to distinguish from other causes of acute-onset amnesia, including posterior circulation strokes, transient epileptic amnesia, psychogenic amnesia, post-traumatic amnesia, and toxic/drug-related amnesia. Here, we describe the general approach to the patient with acute amnesia; summarise the clinical and neuropsychological differences between the potential causes; and, provide practical recommendations to aid diagnosis and management of acute amnesia. Regardless of cause and the dramatic presentation, non-ischaemic acute-onset amnesia generally has a favourable prognosis.

Prediction of 7-year's conversion from subjective cognitive decline to mild cognitive impairment.

Subjective cognitive decline (SCD) is a high-risk yet less understood status before developing Alzheimer's disease (AD). This work included 76 SCD individuals with two (baseline and 7 years later) neuropsychological evaluations and a baseline T1-weighted structural MRI. A machine learning-based model was trained based on 198 baseline neuroimaging (morphometric) features and a battery of 25 clinical measurements to discriminate 24 progressive SCDs who converted to mild cognitive impairment (MCI) at follow-up from 52 stable SCDs. The SCD progression was satisfactorily predicted with the combined features. A history of stroke, a low education level, a low baseline MoCA score, a shrunk left amygdala, and enlarged white matter at the banks of the right superior temporal sulcus were found to favor the progression. This is to date the largest retrospective study of SCD-to-MCI conversion with the longest follow-up, suggesting predictable far-future cognitive decline for the risky populations with baseline measures only. These findings provide valuable knowledge to the future neuropathological studies of AD in its prodromal phase.

Prevalence of Mild Cognitive Impairment in the Lothian Birth Cohort 1936.

BACKGROUND: The Lothian Birth Cohort 1936 (LBC1936) is a highly phenotyped longitudinal study of cognitive and brain ageing. Given its substantial clinical importance, we derived an indicator of mild cognitive impairment (MCI) and amnestic and nonamnestic subtypes at 3 time points. METHODS: MCI status was derived at 3 waves of the LBC1936 at ages 76 (n=567), 79 (n=441), and 82 years (n=341). A general MCI category was derived as well as amnestic MCI (aMCI) and nonamnestic MCI (naMCI). A comparison was made between MCI derivations using normative data from the LBC1936 cohort versus the general UK population. RESULTS: MCI rates showed a proportional increase at each wave between 76 and 82 years from 15% to 18%. Rates of MCI subtypes also showed a proportional increase over time: aMCI 4% to 6%; naMCI 12% to 16%. Higher rates of MCI were found when using the LBC1936 normative data to derive MCI classification rather than UK-wide norms. CONCLUSIONS: We found that MCI and aMCI rates in the LBC1936 were consistent with previous research. However, naMCI rates were higher than expected. Future LBC1936 research should assess the predictive factors associated with MCI prevalence to validate previous findings and identify novel risk factors.

A case report of left atrial myxoma presenting with amnesia.

BACKGROUND: Primary cardiac tumors are rare, and approximately 90% of them are benign. Myxoma is the most common type of these tumors occurring in the left atrium in 75-85% of cases. The tumor can cause the left atrio-ventricular valve obstruction and embolization phenomenon. Case presentation We reported a case of 54-year-old man with complaints of dyspenea and amnesia. In our patient, transthoracic echocardiography revealed a mass of 28*63 mm attached to the upper intra-atrial septum, which was prolapsing through the mitral valve into the left ventricle during diastole, being indicative of the left atrial myxoma. On examination, he was alert and conversant, and no pathological abnormality was observed in the examination of cardiovascular, gastrointestinal, respiratory, hepatic, renal and nervous systems. After myxoma diagnosis, the tumor was removed under cardiac surgery and discharged under good conditions. In the telephone follow-up after discharge, the patient recovered and did not report the disease and surgery complications. CONCLUSIONS: Patients with cardiac myxoma are usually asymptomatic, but they may have manifestations related to the embolism phenomenon or intracardiac obstruction. Therefore, myxoma may represent an emergency. Surgery should be performed as soon as possible. If surgery is delayed, the patient may suffer from serious and irreversible complications, such as stroke and cardiac arrest.

Comparing the Westmead Posttraumatic Amnesia Scale, Galveston Orientation and Amnesia Test, and Confusion Assessment Protocol as Measures of Acute Recovery Following Traumatic Brain Injury.

BACKGROUND: The duration of the acute period of recovery following traumatic brain injury (TBI) remains a widely used criterion for injury severity and clinical management. Consensus regarding its most appropriate definition and assessment method has yet to be established. OBJECTIVE: The present study compared the trajectory of recovery using 3 measures: the Westmead Post-Traumatic Amnesia Scale (WPTAS), the Galveston Orientation and Amnesia Test (GOAT), and the Confusion Assessment Protocol (CAP). Patterns of symptom recovery using the CAP were explored. PARTICIPANTS: Eighty-two participants with moderate to severe TBI in posttraumatic amnesia (PTA) on admission to an inpatient rehabilitation hospital. DESIGN: Prospective longitudinal study. OUTCOME MEASURES: Length of PTA (days), agreement between measures (%, κ coefficient), and pattern of symptom recovery. RESULTS: Participants emerged from PTA earliest on the CAP followed the GOAT, and last on the WPTAS. There was good agreement between the CAP and the GOAT as to PTA status, but both tests had poor agreement with the WPTAS. Of patients considered out of PTA on the CAP, the majority exhibited signs of amnesia on the WPTAS and one-third had clinical levels of agitation. CONCLUSION: The WPTAS identifies a later stage of PTA recovery that requires specialized management due to ongoing amnesia and agitation. The CAP and the GOAT are less sensitive to this extended period of PTA.

A proposal for a new clinical entity: transient epileptic amnesia complex syndrome (TEACS).

Transient epileptic amnesia (TEA) is a special type of temporal lobe epilepsy, the main symptom of which is recurrent amnesia attacks. In the late 1990s, Zeman et al. developed the following diagnostic criteria for TEA: (i) recurrent, witnessed episodes of amnesia; (ii) other cognitive functions remain intact during attacks; and (iii) evidence of epilepsy. It was subsequently reported that patients with TEA almost always demonstrate two other types of memory symptoms: accelerated long-term forgetting (ALF) and autobiographical amnesia (AbA). As a result, it has been recognised that TEA causes at least three characteristic types of amnesia, that is, amnesia attacks, ALF, and AbA. In this report, we present two clinical cases, in which the patients showed symptoms of ALF and/or AbA without suffering any type of epileptic seizure, including amnesia attacks, for a long time. We discuss a syndrome associated with TEA, particularly the relationship between TEA and ALF/AbA, based on our two cases and a review of the literature. In addition, we propose a new clinical entity, which we named 'transient epileptic amnesia complex syndrome (TEACS)' and will help to ensure that physicians recognise the existence of such cases and do not overlook this condition. Furthermore, the following diagnostic criteria for TEACS are proposed. (i) The patient is middle-aged to elderly at onset and has no history of epilepsy. (ii) ALF and/or AbA have been definitively diagnosed. (iii) The ALF and/or AbA precede TEA attacks and/or other epileptic seizures. (iv) Except for the ALF/AbA, the patient's cognitive functions are confirmed to be intact via clinical examinations. (v) There is evidence for a diagnosis of epilepsy. Such evidence can include: (i) wake or sleep electroencephalography; or (ii) a clear response to anti-epileptic drugs. Furthermore, we describe our hypotheses regarding the pathogenesis of ALF/AbA and discuss the relationships between TEACS and other epileptic amnesia-related syndromes.

Electroacupuncture reduces scopolamine-induced amnesia via mediating the miR-210/SIN3A and miR-183/SIN3A signaling pathway.

BACKGROUND: The expression of SIN3A is closely correlated with electroacupuncture (EA) treatment efficacy of scopolamine-induced amnesia (SIA), but its underlying mechanisms remain to be further explored. METHODS: Quantitative real-time PCR was performed to analyze the expression of candidate microRNAs (miRNAs) and SIN3A mRNA in a rat model of SIA. Western blot was carried out to evaluate the differential expression of SIN3A proteins under different circumstances. Luciferase assay was used to explore the inhibitory role of certain miRNAs in SIN3A expression. A novel object recognition (NOR) test was performed to assess the memory function of SIA rats undergoing EA treatment. Immunohistochemistry was carried out to evaluate the expression of SIN3A in the hippocampus of SIA rats. RESULTS: Rno-miR-183-5p, rno-miR-34c-3p and rno-miR-210-3p were significantly up-regulated in SIA rats treated with EA. In addition, rno-miR-183-5p and rno-miR-210-3p exerted an inhibitory effect on SIN3A expression. EA treatment of SIA rats effectively restored the dysregulated expression of rno-miR-183-5p, rno-miR-210-3p and SIN3A. EA treatment also promoted the inhibited expression of neuronal IEGs including Arc, Egr1, Homer1 and Narp in the hippocampus of SIA rats. Accordingly, the NOR test also confirmed the effect of EA treatment on the improvement of memory in SIA rats. CONCLUSION: In summary, the findings of this study demonstrated that scopolamine-induced amnesia was associated with downregulated expression of miR-210/miR-183 and upregulated expression of SIN3A. Furthermore, treatment with EA alleviated scopolamine-induced amnesia in rats and was associated with upregulated expression of miR-210/miR-183 and downregulated expression of SIN3A.

Memory Compensation Strategies in Older People with Mild Cognitive Impairment.

OBJECTIVES: With the rapid growth of the older population worldwide, understanding how older adults with mild cognitive impairment (MCI) use memory strategies to mitigate cognitive decline is important. This study investigates differences between amnestic and nonamnestic MCI subtypes in memory strategy use in daily life, and how factors associated with cognition, general health, and psychological well-being might relate to strategy use. METHODS: One hundred forty-eight participants with MCI (mean age = 67.9 years, SD = 8.9) completed comprehensive neuropsychological, medical, and psychological assessments, and the self-report 'Memory Compensation Questionnaire'. Correlational and linear regression analyses were used to explore relationships between memory strategy use and cognition, general health, and psychological well-being. RESULTS: Memory strategy use does not differ between MCI subtypes (p > .007) despite higher subjective everyday memory complaints in those with amnestic MCI (p = .03). The most marked finding showed that increased reliance-type strategy use was significantly correlated with more subjective memory complaints and poorer verbal learning and memory (p < .01) in individuals with MCI. Moreover, fewer subjective memory complaints and better working memory significantly predicted (p < .05) less reliance strategy use, respectively, accounting for 10.6% and 5.3% of the variance in the model. CONCLUSIONS: In general, the type of strategy use in older adults with MCI is related to cognitive functioning. By examining an individual's profile of cognitive dysfunction, a clinician can provide more personalized clinical recommendations regarding strategy use to individuals with MCI, with the aim of maintaining their day-to-day functioning and self-efficacy in daily life.

Social cognition in an adult epilepsy patient with developmental amnesia.

Reports on social cognition in patients with developmental amnesia resulting from bilateral hippocampal lesions are rare, although the link between social cognition and temporal lobe structures is well established. We present the case of a 23-year-old male epilepsy patient, BM, with developmental amnesia due to perinatal cerebral hypoxia. The patient was examined with neuroimaging and neuropsychological methods and compared to IQ-matched patients with epilepsy to control for effects of epilepsy. In addition, we used a test battery that evaluates emotion recognition and theory of mind to study his social cognition abilities. Structural high-resolution magnetic resonance imaging showed bilateral hippocampal atrophy. The comparison to controls showed that, in addition to the well-documented memory disorders in developmental amnesia, BM showed remarkable deficits in 9 out of 17 social cognitive tasks assessing emotion recognition and theory of mind. In contrast, BM's performance on tasks of executive functions was largely preserved. The relevance of deficits in social cognition for patients with developmental amnesia is discussed.

Opiate analgesics and testing of post traumatic amnesia in school-aged children.

OBJECTIVE: To assess the validity of the Westmead PTA scale in school-aged children treated with opiate analgesics. METHOD: Twenty-eight hospitalized children without brain injury, aged between 8 and 16 years treated with opiate analgesics for pain relief following surgery were tested on the Westmead PTA scale. Pain and stress levels were also self-reported each day. RESULTS: Only 29% (n = 7) of children assessed over four days obtained a maximum score of 12/12 on three consecutive days, thus 71% would have been deemed to have been in PTA when they were not. The percentage of children who obtained a maximum score significantly decreased over consecutive days of assessment, due to an increase in error rate on picture memory items. Self-reported pain and stress ratings were not correlated with PTA scores. CONCLUSIONS: Opiate analgesia can disrupt performance on the Westmead PTA scale in school-aged children resulting in a high false-positive error rate. It is therefore important to record pain medication schedules and interpret results cautiously when opiate analgesia is used following a TBI. Alteration of the method of administration of the memory items should be researched as this may increase the validity of the scale for children with TBI treated with opiate analgesics.

Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.

OBJECTIVE: (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide. Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD. However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD. In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC). Additionally, the potential association between IM and clinical characteristics of AD was evaluated. METHODS: A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients. RESULTS: The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC. And the microbial composition was distinct among aMCI, AD and healthy control groups. Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC. In addition, similar alterations were observed at the order, class and family levels of these two phyla. And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients. Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes. Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients. Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925). Notably, the models based on the abundance of family Enterobacteriaceae could distinguish AD from both aMCI (AUC = 0.688) and HC (AUC = 0.698). CONCLUSIONS: Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects. These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.

Visual Object Discrimination Impairment as an Early Predictor of Mild Cognitive Impairment and Alzheimer's Disease.

OBJECTIVE: Detection of cognitive impairment suggestive of risk for Alzheimer's disease (AD) progression is crucial to the prevention of incipient dementia. This study was performed to determine if performance on a novel object discrimination task improved identification of earlier deficits in older adults at risk for AD. METHOD: In total, 135 participants from the 1Florida Alzheimer's Disease Research Center [cognitively normal (CN), Pre-mild cognitive impairment (PreMCI), amnestic mild cognitive impairment (aMCI), and dementia] completed a test of object discrimination and traditional memory measures in the context of a larger neuropsychological and clinical evaluation. RESULTS: The Object Recognition and Discrimination Task (ORDT) revealed significant differences between the PreMCI, aMCI, and dementia groups versus CN individuals. Moreover, relative risk of being classified as PreMCI rather than CN increased as an inverse function of ORDT score. DISCUSSION: Overall, the obtained results suggest that a novel object discrimination task improves the detection of very early AD-related cognitive impairment, increasing the window for therapeutic intervention. (JINS, 2019, 25, 688-698).