Translocator protein (TSPO) genotype does not change cerebrospinal fluid levels of glial activation, axonal and synaptic damage markers in early Alzheimer's disease.

BACKGROUND: PET imaging of the translocator protein (TSPO) is used to assess in vivo brain inflammation. One of the main methodological issues with this method is the allelic dependence of the radiotracer affinity. In Alzheimer's disease (AD), previous studies have shown similar clinical and patho-biological profiles between TSPO genetic subgroups. However, there is no evidence regarding the effect of the TSPO genotype on cerebrospinal-fluid biomarkers of glial activation, and synaptic and axonal damage. METHOD: We performed a trans-sectional study in early AD to compare cerebrospinal-fluid levels of GFAP, YKL-40, sTREM2, IL-6, IL-10, NfL and neurogranin between TSPO genetic subgroups. RESULTS: We recruited 33 patients with early AD including 16 (48%) high affinity binders, 13 (39%) mixed affinity binders, and 4/33 (12%) low affinity binders. No difference was observed in terms of demographics, and cerebrospinal fluid levels of each biomarker for the different subgroups. CONCLUSION: TSPO genotype is not associated with a change in glial activation, synaptic and axonal damage in early AD. Further studies with larger numbers of participants will be needed to confirm that the inclusion of specific TSPO genetic subgroups does not introduce selection bias in studies and trials of AD that combine TSPO imaging with cerebrospinal fluid biomarkers.

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer's disease.

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer's disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression.

What are the neural correlates of dissociative amnesia? A systematic review of the functional neuroimaging literature.

Aim: Dissociative amnesia is an emblematic psychiatric condition in which patients experience massive memory loss ranging from focal to global amnesia. This condition remains poorly understood and this review aims to investigate the neuroanatomical feature of this disease. Methods: We conducted a systematic review of the scientific literature available on PubMed, up to December 1, 2022, using a combination of keywords referring to dissociative amnesia. We included every scientific report involving patients undergoing a functional imaging procedure. Results: Twenty-two studies met our inclusion criteria (gathering 49 patients). Only one was a controlled study with a large sample. The other 21 were case reports and case series. In resting state, neuroimaging studies mostly showed a hypo-activated right inferolateral prefrontal cortex, associated with limbic hypoactivity and lesser activation of the hippocampal and para-hippocampal structures. The patients also presented abnormal patterns of cerebral activation when performing memory tasks. When testing recognition of memories from the amnestic period, patients showed increased activation across temporal areas (hippocampal and para-hippocampal gyri) and the limbic network. When trying to recollect memories from an amnestic period compared to a non-amnestic period, patients failed to activate these structures efficiently. Most of these patterns tended to return to normal when symptoms resolved. Conclusion: This review identified a paucity of controlled studies in the field of dissociative amnesia neuroimaging, which restricts the extrapolation of results. Patients with dissociative amnesia present a broad prefronto-temporo-limbic network dysfunction. Some of the brain areas implicated in this network might represent potential targets for innovative treatments.

A prospective behavioral and imaging study exploring the impact on long-term memory of radiotherapy delivered for a brain tumor in childhood and adolescence.

BACKGROUND: Posterior fossa tumors represent two thirds of brain tumors in children. Although progress in treatment has improved survival rates over the past few years, long-term memory impairments in survivors are frequent and have an impact on academic achievement. The hippocampi, cerebellum and cerebellar-cortical networks play a role in several memory systems. They are affected not only by the location of the tumor itself and its surgical removal, but also by the supratentorial effects of complementary treatments, particularly radiotherapy. The IMPALA study will investigate the impact of irradiation doses on brain structures involved in memory, especially the hippocampi and cerebellum. METHODS/DESIGN: In this single-center prospective behavioral and neuro-imaging study, 90 participants will be enrolled in three groups. The first two groups will include patients who underwent surgery for a posterior fossa brain tumor in childhood, who are considered to be cured, and who completed treatment at least 5 years earlier, either with radiotherapy (aggressive brain tumor; Group 1) or without (low-grade brain tumor; Group 2). Group 3 will include control participants matched with Group 1 for age, sex, and handedness. All participants will perform an extensive battery of neuropsychological tests, including an assessment of the main memory systems, and undergo multimodal 3 T MRI. The irradiation dose to the different brain structures involved in memory will be collected from the initial radiotherapy dosimetry. DISCUSSION: This study will provide long-term neuropsychological data about four different memory systems (working memory, episodic memory, semantic memory, and procedural memory) and the cognitive functions (attention, language, executive functions) that can interfere with them, in order to better characterize memory deficits among the survivors of brain tumors. We will investigate the correlations between neuropsychological and neuroimaging data on the structural (3DT1), microstructural (DTI), functional (rs-fMRI), vascular (ASL) and metabolic (spectroscopy) impact of the tumor and irradiation dose. This study will thus inform the setting of dose constraints to spare regions linked to the development of cognitive and memory functions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04324450, registered March 27, 2020, updated January 25th, 2021. Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04324450.

Hidden Objective Memory Deficits Behind Subjective Memory Complaints in Patients With Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: The aim of this work was to test the hypothesis that patients with temporal lobe epilepsy (TLE) with subjective initial memory complaints (not confirmed by an objective standard assessment) and various phenotypes also show objective very long-term memory deficit with accelerated long-term forgetting. We tested patients with TLE with 2 surprise memory tests after 3 weeks: the standard Free and Cued Selective Reminding Test (FCSRT) and Epireal, a new test specifically designed to capture more ecologic aspects of autobiographical memory. METHODS: Forty-seven patients with TLE (12 with hippocampal sclerosis, 12 with amygdala enlargement, 11 with extensive lesions, 12 with normal MRI) who complained about their memory, but for whom the standard neuropsychological assessment did not reveal any memory impairment after a standard delay of 20 minutes, underwent 2 surprise memory tests after 3 weeks. They were compared to 35 healthy controls. RESULTS: After 3 weeks, FCSRT and Epireal recall scores were significantly lower in patients than in controls (p < 0.001). There was no significant correlation between FCSRT and Epireal scores (p = 0.99). Seventy-six percent of patients with TLE had objective impairment on at least 1 of these very long-term memory tests, regardless of the existence and type of lesion or response to antiseizure medication. Easily applicable, Epireal had a higher effect size, detected deficits in 28% more patients, and is a useful addition to the standard workup. DISCUSSION: Assessing long-term memory should be broadened to a wide spectrum of patients with TLE with a memory complaint, regardless of the epileptic syndrome, regardless of whether it is associated with a lesion. This could lead to rethinking TLE nosology associated with memory.

Memory impairment following intentional self-poisoning with benzodiazepines: Should we pay more attention to attention?

STUDY HYPOTHESIS: In cases where patients attempt suicide through intentional self-poisoning, they often ingest drugs such as benzodiazepines that alter the central nervous system and memory. This is problematic, given that experts recommend the recovery of a patient's cognitive capacity before any psychiatric assessment is conducted. A previous pilot study by our group showed that cognitive tests focusing on attention are the most valuable when it comes to determining whether sufficient cognitive recovery has occurred to ensure that patients will remember the assessment after intentional self-poisoning with benzodiazepines. The main aim of our study was to determine cognitive predictors of the recall of the psychiatric assessment after a suicide attempt. The second aim was to determine the threshold for episodic memory. METHODS: We recruited 97 patients admitted for intentional self-poisoning. At the time of the psychiatric assessments, we quantified plasma benzodiazepine levels and performed a cognitive assessment. We then used a linear regression model to identify the associations in a control and a benzodiazepine group between cognitive functions and episodic memory scores obtained 24 hours after psychiatric assessment. RESULTS: Our model accounted for 28% and 37%, respectively, of the variance in memory in the control and benzodiazepine groups. The most significant correlations were found for the Wechsler Adult Intelligence Scale coding test in both groups. In the control group, tests such as visual and verbal memory were also associated with recall. CONCLUSIONS: Benzodiazepines particularly affect memory by impairing what is remembered of attentional tests. These are, however, the most suitable cognitive tests for predicting recall of the memory assessment.

Pauses During Autobiographical Discourse Reflect Episodic Memory Processes in Early Alzheimer's Disease.

There is a large body of research on discourse production in Alzheimer's disease (AD). Some studies have focused on pause production, revealing that patients make extensive use of pauses during speech. This has been attributed to lexical retrieval difficulties, but pausing may also reflect other forms of cognitive impairment as it increases with cognitive load. The aim of the present study was to analyze autobiographical discourse impairment in AD from a broad perspective, looking at pausing behavior (frequency, duration, and location). Our first objective was to characterize discourse changes in mild cognitive impairment (MCI) due to AD. Our second objective was to determine the cognitive and neuroanatomical correlates of these changes. Fifteen patients with MCI due to AD and 15 matched cognitively normal controls underwent an ecological episodic memory task, a full neuropsychological assessment, and a 3D T1-weighted MRI scans. Autobiographical discourse collected from the ecological episodic memory task was recorded, transcribed, and analyzed, focusing on pausing. Intergroup comparisons showed that although patients did not produce more pauses than controls overall, they did make more between-utterance pauses. The number of these specific pauses was positively correlated with patients' episodic memory performance. Furthermore, neuroimaging analysis showed that, in the patient group, their use was negatively correlated with frontopolar area (BA 10) grey matter density. This region may therefore play an important role in the planning of autobiographical discourse production. These findings demonstrate that pauses in early AD may reflect a compensatory mechanism for improving mental time travel and memory retrieval.

Neuropsychological outcome after carbon monoxide exposure following a storm: a case-control study.

BACKGROUND: The cognitive consequences of carbon monoxide (CO) poisoning are well described. However, most studies have been carried out without an ad-hoc group of control subjects. The main aim of this study was to evaluate cognitive and psychiatric outcome after CO exposure during the storm Klaus in the South West of France (January 2009) in a homogeneous group of patients compared to a group of 1:1 paired controls. METHODS: Patients and controls were asked to fill out questionnaires about quality of life and cognitive complaints. They then underwent a cognitive assessment derived from the Carbon Monoxide Neuropsychological Screening Battery. Psychiatric assessment was performed using subtests of the Mini International Neuropsychiatric Interview. RESULTS: 38 patients and 38 paired controls were included (mean age 38.8 years) and evaluated 51 days after the poisoning. No difference was found between groups on the cognitive complaint questionnaire but patients had a lower quality of life than controls. Patients showed significantly lower cognitive performance than controls on processing speed, mental flexibility, inhibition and working and verbal episodic memories. Patients were more depressed than controls, and suffered more from post-traumatic stress disorder. CONCLUSIONS: We report the first study investigating cognitive and psychiatric outcome in consecutive patients after CO poisoning during a natural disaster, using a group comparison method. CO poisoning during storms needs to be dealt with adequately and clinicians should be aware of its possible consequences.

Clinical and imaging evidence of zolpidem effect in hypoxic encephalopathy.

We conducted a randomized, double-blind, placebo-controlled, single-patient (N = 1) trial to evaluate the efficacy of zolpidem in a 48-year-old woman with an akinetic mutism. Motor and cognitive examinations and functional imaging were performed. Acute administration of zolpidem markedly improved motor performance and neuropsychological status. Cerebral metabolism ((18)F-fluorodeoxyglucose positron emission tomography) increased in postrolandic territories and in frontal cortex. Using the H(2) (15)O positron emission tomography, we found a drug-induced activation in the anterior cingulate and orbitofrontal cortices. Zolpidem induced a transient improvement in motor and cognitive performances. This paradoxical effect could result from an activation of limbic loops modulating motivational processes.