-
Alzheimer's Research & Therapy May 2024As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal...
BACKGROUND
As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD.
METHODS
mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK) mice. Animals' cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation.
RESULTS
Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists.
CONCLUSIONS
Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.
Topics: Animals; Alzheimer Disease; Mice; Receptor, Cholecystokinin B; Amnesia, Anterograde; Cholecystokinin; Mice, Transgenic; Disease Models, Animal; Entorhinal Cortex; Male; Mice, Knockout; Mice, Inbred C57BL; Long-Term Potentiation; Hippocampus; Aging
PubMed: 38750512
DOI: 10.1186/s13195-024-01472-1 -
European Journal of Psychotraumatology 2024While several studies documented a positive correlation between childhood maltreatment severity and dissociation severity, it is currently unknown whether specific...
While several studies documented a positive correlation between childhood maltreatment severity and dissociation severity, it is currently unknown whether specific dissociative symptoms cluster together among individuals with childhood trauma histories ranging from none to severe. We aimed to explore symptom constellations across the whole spectrum of dissociative processing from patients with severe dissociative disorders to healthy controls and relate these to maltreatment severity and sociodemographic characteristics. We employed latent profile analysis to explore symptom profiles based on five subscales, measuring absorption, depersonalization, derealization, somatoform and identity alteration, based on the 20 items of the German short version of the Dissociative Experiences Scale-II (20) in a large aggregate sample ( = 3,128) overrepresenting patients with trauma-related disorders. We then related these profiles to maltreatment severity as measured by the five subscales of the Childhood Trauma Questionnaire as well as sociodemographic characteristics. Based on the five FDS subscales, six clusters differentiated by symptom severity, but not symptom constellations, were identified. Somatoform dissociation varied in accordance with the remaining symptom clusters. The cluster with the highest overall symptom severity entailed nearly all subjects diagnosed with Dissociative Identity Disorder and was characterized by extreme levels of childhood maltreatment. Both abuse and neglect were predictive of cluster membership throughout. The higher the severity of dissociative processing in a cluster, the more subjects reported high severity and multiplicity of childhood maltreatment. However, some subjects remain resilient to the development of dissociative processing although they experience extreme childhood maltreatment.
Topics: Humans; Dissociative Disorders; Female; Male; Adult; Surveys and Questionnaires; Adult Survivors of Child Abuse; Middle Aged; Adverse Childhood Experiences; Child Abuse; Germany; Psychiatric Status Rating Scales; Child
PubMed: 38739008
DOI: 10.1080/20008066.2024.2348345 -
BMJ Neurology Open 2024Isolated infarction of the fornix is a relatively rare stroke syndrome frequently associated with amnesia. The long-term cognitive outcome in cases of acute fornix...
INTRODUCTION
Isolated infarction of the fornix is a relatively rare stroke syndrome frequently associated with amnesia. The long-term cognitive outcome in cases of acute fornix infarction is poorly understood. This is largely due to the limited number of case studies that have documented cognitive outcomes beyond the acute recovery phase on quantifiable neuropsychological measures. We describe a patient who developed acute amnesia and was subsequently diagnosed on cerebral MRI with bilateral infarction in the anterior columns of the fornix.
METHOD
Comprehensive neuropsychological review was undertaken prospectively at baseline, early and late phases of recovery.
RESULTS
At 9 months post-stroke, there was some reduction in the severity of memory dysfunction, but a significant anterograde amnesia persisted.
CONCLUSION
This is one of the very few cases in the literature where neuropsychological function has been comprehensively and serially examined over the first year post-isolated bilateral fornix infarction. It is concluded that amnesia can persist well beyond 6 months in these cases, with associated functional impairment in daily life.
PubMed: 38736581
DOI: 10.1136/bmjno-2024-000655 -
Dementia and Neurocognitive Disorders Apr 2024This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether...
BACKGROUND AND PURPOSE
This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities.
METHODS
We evaluated the brain MRI data from 87 TGA patients and 20 age- and sex-matched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects.
RESULTS
TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected <0.05).
CONCLUSIONS
TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.
PubMed: 38720827
DOI: 10.12779/dnd.2024.23.2.89 -
Neurologia Medico-chirurgica Jun 2024It has been reported that various clinical criteria indicate computed tomography (CT) examination for mild head injury (MHI). However, the decision to perform CT for MHI...
It has been reported that various clinical criteria indicate computed tomography (CT) examination for mild head injury (MHI). However, the decision to perform CT for MHI largely depends on the physician. Data on severe head injuries is available in sources such as the Japan Neurotrauma Data Bank, but only a few data has been collected on MHI. A total of 1688 patients with MHI (Glasgow Coma Scale 14 and 15) treated at our hospital from June 2017 to May 2019 were reviewed. CT was performed in 1237 patients (73.28%), and intracranial hemorrhage was detected in 50 patients. Three patients deteriorated, and all were surgically treated. Statistical analysis of the presence or absence of acute intracranial hemorrhage and "risk factors for complications of intracranial lesions in MHI" showed significant differences in unclear or ambiguous accident history (p = 0.022), continued post-traumatic amnesia (p < 0.01), trauma above the clavicles including clinical signs of skull fracture (skull base or depressed skull fracture) (p = 0.012), age <60 years (p < 0.01), coagulation disorders (p < 0.01), and alcohol or drug intoxication (p < 0.01). The 453 patients who did not satisfy these risk factors included only one patient with intracranial hemorrhage, so the negative predictive value was 99.78%. This study shows that the "risk factors for complications of intracranial lesions in MHI" are effective criteria for excluding acute intracranial hemorrhage and CT should be actively considered for patients with the above factors that showed significant differences.
Topics: Humans; Male; Female; Middle Aged; Tomography, X-Ray Computed; Adult; Aged; Young Adult; Glasgow Coma Scale; Aged, 80 and over; Adolescent; Retrospective Studies; Craniocerebral Trauma; Risk Factors; Intracranial Hemorrhages; Japan; Child; Brain Concussion
PubMed: 38719579
DOI: 10.2176/jns-nmc.2023-0297 -
Alzheimer's Research & Therapy May 2024The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in...
BACKGROUND
The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls.
METHODS
Seventy-two participants (23 early amnestic-AD patients, 17 suspected-LATE, 17 FTD patients, defined by a clinical-biological diagnosis reinforced by amyloid and tau PET imaging, and 15 controls) underwent neuropsychological assessment and 3T brain MRI. We analyzed the locus coeruleus signal intensity (LC-I) and the NBM volume as well as their relation with cognition and with medial temporal/cortical atrophy.
RESULTS
We found significantly lower LC-I and NBM volume in amnestic-AD and suspected-LATE in comparison with controls. In FTD, we also observed lower NBM volume but a slightly less marked alteration of the LC-I, independently of the temporal or frontal phenotype. NBM volume was correlated with the global cognitive efficiency in AD patients. Strong correlations were found between NBM volume and that of medial temporal structures, particularly the amygdala in both AD and FTD patients.
CONCLUSIONS
The alteration of LC and NBM in amnestic-AD, presumed-LATE and FTD suggests a common vulnerability of these structures to different proteinopathies. Targeting the noradrenergic and cholinergic systems could be effective therapeutic strategies in LATE and FTD.
Topics: Humans; Frontotemporal Dementia; Male; Locus Coeruleus; Alzheimer Disease; Female; Aged; Magnetic Resonance Imaging; Basal Nucleus of Meynert; Middle Aged; Neuropsychological Tests; Amnesia; Positron-Emission Tomography
PubMed: 38702802
DOI: 10.1186/s13195-024-01466-z -
Brain and Behavior May 2024Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we...
A comprehensive assessment of the cholinergic-supporting and cognitive-enhancing effects of Rosa damascena Mill. (Damask rose) essential oil on scopolamine-induced amnestic rats.
INTRODUCTION
Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues.
METHODS
The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 μL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor.
RESULTS
According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically -citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active-state human M mAChR and anchored here chiefly by hydrogen-bonding and alkyl-π interactions.
CONCLUSION
Our findings offer a solid experimental foundation for future RDEO-based medicinal product development for patients suffering from AD.
Topics: Animals; Scopolamine; Rats; Amnesia; Oils, Volatile; Male; Rosa; Brain-Derived Neurotrophic Factor; Acetylcholinesterase; Receptor, Muscarinic M1; Rats, Wistar; Nootropic Agents; Disease Models, Animal; Brain; Cognition; Maze Learning
PubMed: 38688895
DOI: 10.1002/brb3.3507 -
BMJ Open Apr 2024To examine non-sport- and sport-related concussion severity, clinical care frequency and delayed reporting in relation to recovery duration among collegiate athletes.
OBJECTIVES
To examine non-sport- and sport-related concussion severity, clinical care frequency and delayed reporting in relation to recovery duration among collegiate athletes.
DESIGN
Retrospective cohort study.
SETTING
Pac-12 varsity collegiate athletes.
PARTICIPANTS
461 collegiate male and female athletes PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence of sport-related concussion (SRC) and non-sport-related concussion (NRC) were collected as well as times to recovery and return-to-play (RTP), symptom score and symptom severity and reported a loss of consciousness (LOC), retrograde amnesia (RGA) and post-traumatic amnesia (PTA) following concussion incidence.
RESULTS
Among 461 concussions, 388 (84%) occurred within sport and 73 (16%) occurred outside of sport. NRC, on average, required 3.5 more days to become asymptomatic (HR: 0.73, 95%confidence interval: 0.56 to 0.96, p=0.02) and 7 more days to RTP (HR: 0.64, 95% confidence interval: 0.49 to 0.85, p<0.01) compared with SRC. NRC were associated with an increase of 1.83 (p=0.07) symptoms reported at the time of diagnosis, an increase of 6.95 (p=0.06) in symptom severity and a higher prevalence of reported LOC (22% NRC vs. 3% SRC, p0.001), PTA (15% NRC vs. 5% SRC, p<.01) and RGA (10% NRC vs. 4% SRC, p0.06), compared with SRC. There was no significant difference in clinical care (p0.28) or immediate reporting (p=0.35) between NRC and SRC.
CONCLUSION
NRC were associated with greater severity and longer recovery duration when compared with SRC in a cohort of collegiate athletes.
Topics: Humans; Male; Retrospective Studies; Brain Concussion; Female; Athletic Injuries; Young Adult; Athletes; Return to Sport; Recovery of Function; Adolescent; Time Factors; Incidence; Universities
PubMed: 38684271
DOI: 10.1136/bmjopen-2023-079953 -
Clinical Case Reports May 2024Takotsubo syndrome and transient global amnesia can occur simultaneously, not only in the context of acute but also long-standing emotional stress. Probably,...
Takotsubo syndrome and transient global amnesia can occur simultaneously, not only in the context of acute but also long-standing emotional stress. Probably, hypothyroidism and migraine make the patient more susceptible to both of these disorders.
PubMed: 38681042
DOI: 10.1002/ccr3.8797 -
Journal of Neuroinflammation Apr 2024Identifying individuals with intracranial injuries following mild traumatic brain injury (mTBI), i.e. complicated mTBI cases, is important for follow-up and...
Chronic immunosuppression across 12 months and high ability of acute and subacute CNS-injury biomarker concentrations to identify individuals with complicated mTBI on acute CT and MRI.
BACKGROUND
Identifying individuals with intracranial injuries following mild traumatic brain injury (mTBI), i.e. complicated mTBI cases, is important for follow-up and prognostication. The main aims of our study were (1) to assess the temporal evolution of blood biomarkers of CNS injury and inflammation in individuals with complicated mTBI determined on computer tomography (CT) and magnetic resonance imaging (MRI); (2) to assess the corresponding discriminability of both single- and multi-biomarker panels, from acute to chronic phases after injury.
METHODS
Patients with mTBI (n = 207), defined as Glasgow Coma Scale score between 13 and 15, loss of consciousness < 30 min and post-traumatic amnesia < 24 h, were included. Complicated mTBI - i.e., presence of any traumatic intracranial injury on neuroimaging - was present in 8% (n = 16) on CT (CT+) and 12% (n = 25) on MRI (MRI+). Blood biomarkers were sampled at four timepoints following injury: admission (within 72 h), 2 weeks (± 3 days), 3 months (± 2 weeks) and 12 months (± 1 month). CNS biomarkers included were glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and tau, along with 12 inflammation markers.
RESULTS
The most discriminative single biomarkers of traumatic intracranial injury were GFAP at admission (CT+: AUC = 0.78; MRI+: AUC = 0.82), and NFL at 2 weeks (CT+: AUC = 0.81; MRI+: AUC = 0.89) and 3 months (MRI+: AUC = 0.86). MIP-1β and IP-10 concentrations were significantly lower across follow-up period in individuals who were CT+ and MRI+. Eotaxin and IL-9 were significantly lower in individuals who were MRI+ only. FGF-basic concentrations increased over time in MRI- individuals and were significantly higher than MRI+ individuals at 3 and 12 months. Multi-biomarker panels improved discriminability over single biomarkers at all timepoints (AUCs > 0.85 for admission and 2-week models classifying CT+ and AUC ≈ 0.90 for admission, 2-week and 3-month models classifying MRI+).
CONCLUSIONS
The CNS biomarkers GFAP and NFL were useful single diagnostic biomarkers of complicated mTBI, especially in acute and subacute phases after mTBI. Several inflammation markers were suppressed in patients with complicated versus uncomplicated mTBI and remained so even after 12 months. Multi-biomarker panels improved diagnostic accuracy at all timepoints, though at acute and 2-week timepoints, the single biomarkers GFAP and NFL, respectively, displayed similar accuracy compared to multi-biomarker panels.
Topics: Humans; Male; Biomarkers; Female; Magnetic Resonance Imaging; Adult; Middle Aged; Tomography, X-Ray Computed; Brain Concussion; Young Adult; Neurofilament Proteins; Glial Fibrillary Acidic Protein; Aged; Time Factors
PubMed: 38678300
DOI: 10.1186/s12974-024-03094-8