Impact of antithrombotic therapy on acute and delayed intracranial haemorrhage and evaluation of the need of short-term hospitalisation based on CT findings after mild traumatic brain injury: experience from an oral and maxillofacial surgery unit.

PURPOSE: The primary aim was to compare the prevalence of acute and delayed intracranial haemorrhage (ICH) following mild traumatic brain injury (mTBI) in patients on antithrombotic medication referred to a clinic for oral and plastic maxillofacial surgery. The secondary aim was to evaluate the need for short-term hospitalisation based on initial radiological and clinical findings. METHODS: This was an observational retrospective single-centre study of all patients on antithrombotic medication who were admitted to our department of oral and plastic maxillofacial surgery with mTBI over a 5 year period. Demographic and anamnesis data, injury characteristics, antithrombotic medication, radiological findings, treatment, and outcome were analysed. Patients were divided into the following four groups based on their antithrombotic medication: (1) single antiplatelet users, (2) vitamin K antagonist users, (3) direct oral anticoagulant users, and (4) double antithrombotic users. All patients underwent an emergency cranial CT (CT0) at admission. Based on clinical and radiological evaluation, different treatment protocols were applied. Patients with positive CT0 findings and patients with secondary neurological deterioration received a control CT (CT1) before discharge. Acute and delayed ICH and patient's outcome during hospitalisation were evaluated using descriptive statistical analysis. RESULTS: A total of 696 patients (mean age, 71.6 years) on antithrombotic medication who presented at our department with mTBI were included in the analysis. Most injuries were caused by a ground-level fall (76.9%). Thirty-six patients (5.1%) developed an acute traumatic ICH, and 47 intracerebral lesions were detected by radiology-most of these in patients taking acetylsalicylic acid. No association was detected between ICH and antithrombotic medication (p = 0.4353). In total, 258 (37.1%) patients were admitted for 48 h in-hospital observation. The prevalence of delayed ICH was 0.1%, and the mortality rate was 0.1%. Multivariable analysis identified a Glasgow Coma Scale (GCS) of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea as clinical characteristics significantly associated with an increased risk of acute ICH, whereas age, sex, and trauma mechanism were not associated with ICH prevalence. Of the 39 patients who underwent a control CT1, most had a decreasing or at least constant intracranial lesion; in three patients, intracranial bleeding increased but was not clinically relevant. CONCLUSION: According to our experience, antithrombotic therapy does not increase the rate of ICH after mTBI. A GCS of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea are indicators of higher ICH risk. A second CT scan is more effective in patients with secondary neurological deterioration. Initial CT findings were not clinically relevant and should not indicate in-hospital observation.

The relationship between semantic and episodic memory: evidence from a case of severe anterograde amnesia.

It is increasingly being recognized that new declarative, consciously accessible information can be learned in anterograde amnesia, but it is not clear whether this learning is supported by episodic or semantic memory. We report a case of a 55-year-old man who experienced severe amnesia after limited damage to the medial temporal lobe following neurosurgical complications. His general cognitive performance and knowledge of new French words and public events that occurred before and after the onset of amnesia were assessed. Performance remained satisfactory on post-morbid vocabulary and public events, with a drop in performance observed for very recent public events only, while knowledge of very recent vocabulary was comparable to that of the control subjects. The implications of these findings for our understanding of the underlying learning mechanisms are discussed. This is the first report of acquisition of consciously accessible postmorbid knowledge of public events in a patient with severe amnesia.

Memory for the News: Does Event Transience Matter?

BACKGROUND: Health providers frequently probe patients' recall of current and/or remote news events to determine the extent of memory loss. Impaired memory for transient events (ie, in the news for a circumscribed time) may provide information regarding the onset of cognitive impairment. OBJECTIVE: To use the Transient News Events Test (TNET) to explore how memory changes over time in both older adults with cognitive impairment (CI) and noncognitively impaired (NCI) older adults. We also investigated the role of episodic and semantic memory on TNET performance. METHOD: Sixty-seven older adults completed the TNET as part of a comprehensive neuropsychological assessment. Analyses included t tests to evaluate group differences for TNET score and correlations between TNET and neuropsychological measures, including episodic and semantic memory tests. RESULTS: NCI adults demonstrated better memory for TNET items than adults with CI. The NCI and CI groups did not differ regarding memory for remote events; however, the CI group exhibited worse memory for recent events. There was a significant association between TNET score and the capacity for episodic and semantic memory in the CI group. In the NCI group, TNET score was significantly associated with episodic memory. CONCLUSION: Findings support the use of transient news events to assess remote memories in older adults. Novel remote memory measures broaden the scope of memory assessment far beyond what is feasible with traditional neuropsychological assessment and may provide insight into the onset of memory changes.

A model for estimating the brainstem volume in normal healthy individuals and its application to diffuse axonal injury patients.

Diffuse axonal injury (DAI) is a subtype of traumatic brain injury that causes acute-phase consciousness disorders and widespread chronic-phase brain atrophy. Considering the importance of brainstem damage in DAI, a valid method for evaluating brainstem volume is required. We obtained volume measurements from 182 healthy adults by analyzing T1-weighted magnetic resonance images, and created an age-/sex-/intracranial volume-based quantitative model to estimate the normal healthy volume of the brainstem and cerebrum. We then applied this model to the volume measurements of 22 DAI patients, most of whom were in the long-term chronic phase and had no gross focal injury, to estimate the percentage difference in volume from the expected normal healthy volume in different brain regions, and investigated its association with the duration of posttraumatic amnesia (which is an early marker of injury severity). The average loss of the whole brainstem was 13.9%. Moreover, the percentage loss of the whole brainstem, and particularly of the pons and midbrain, was significantly negatively correlated with the duration of posttraumatic amnesia. Our findings suggest that injury severity, as denoted by the duration of posttraumatic amnesia, is among the factors affecting the chronic-phase brainstem volume in patients with DAI.

How May a Brief Seizure Lead to Prolonged Epileptic Amnesia?

Pure amnestic seizures are defined as self-limited episodes with isolated, anterograde memory loss and have been attributed to bilateral dysfunction of mesial temporal structures. This type of seizure can occur in patients with different forms of temporal lobe epilepsy and has been more recently associated with a late-onset epileptic syndrome, called transient epileptic amnesia (TEA). The mechanisms of such prolonged manifestations are not well known and notably its ictal or post-ictal origin remains poorly understood. We report a case of prolonged anterograde amnesia (lasting several hours) following a brief seizure induced by stimulation of the left entorhinal cortex, recorded during stereo-EEG (SEEG). This episode was associated with prolonged changes in the intracerebral EEG signal complexity (entropy) within bilateral mesial temporal structures, particularly the entorhinal cortices, with a progressive normalization paralleling the clinical recovery. Our case shows that long-lasting (hours) memory impairment may follow brief seizure that led to prolonged electrophysiological signals alterations in bilateral mesial temporal structures.

Transient global amnesia - hippocampal lesions in magnetic resonance imaging.

BACKGROUND: Transient global amnesia is a benign syndrome characterized by a sudden onset loss of anterograde amnesia with full recovery. Magnetic resonance of the brain including diffusion-weighted imaging of patients with transient global amnesia revealed the presence of punctate hyperintense signal abnormalities in the hippocampus. OBJECTIVE: Analysis of the presence of hippocampal lesions in brain magnetic resonance imaging in patients with transient global amnesia and the possible influence of additional factors on their appearance. METHODS: In this retrospective, an observational study we assessed brain magnetic resonance imaging in 38 consecutive patients with transient global amnesia. The incidence of brain magnetic resonance imaging lesions was analyzed for the coexisting cardiovascular risk factors and precipitating events. RESULTS: Hippocampal brain magnetic resonance imaging lesions were detected in 47% of patients with transient global amnesia. Of those, 65% had unilateral lesions, 82% were left-sided, and 28% were right-sided. Most lesions were located in the CA1 subfield. The incidence of hypertension in patients with transient global amnesia was higher than in the general population. Stress and exercise preceded the onset of transient global amnesia only in 13% and 16% of patients, respectively. There was no higher incidence of migraine in transient global amnesia patients (13%). CONCLUSIONS: We found that nearly 50% of patients with transient global amnesia had hyperintense hippocampal brain magnetic resonance imaging lesions. In addition to hypertension, individuals with transient global amnesia had similar cardiovascular risk factors as the general population. We did not identify any precipitating events prior to the onset of transient global amnesia.

Network localization of transient global amnesia beyond the hippocampus.

BACKGROUND: Transient global amnesia is common in the older adult, but the cause and mechanism remain unclear. Focal brain lesions allow for causal links between the lesion location and resulting symptoms, and we based on the reported TGA-causing lesions and used lesion network mapping to explore the causal neuroanatomical substrate of TGA. METHODS: Fifty-one cases of transient global amnesias with DWI lesions from the literature were identified, and clinical data were extracted and analyzed. Next, we mapped each lesion volume onto a reference brain and computed the network of regions functionally connected to each lesion location using a large normative connectome dataset. RESULTS: Lesions primarily occurred in the hippocampus, and in addition to the hippocampus, there are also other locations of TGA-causing lesions such as the cingulate gyrus, anterior thalamic nucleus (ATN), putamen, caudate nucleus, corpus callosum, fornix. More than 90% of TGA-causing lesions inside the hippocampus were functionally connected with the default mode network (DMN). CONCLUSION: Structural abnormality in the hippocampus was the most consistently reported in TGA, and besides the hippocampus, lesions occurring at several other brain locations also could cause TGA. The DMN may also be involved in the pathophysiology of TGA. According to the clinical and neuroimaging characteristics, TGA may be a syndrome with multiple causes and cannot be treated simply as a subtype of TIA.

Shared and specific dynamics of brain activity and connectivity in amnestic and nonamnestic mild cognitive impairment.

AIMS: The present study aimed to compare temporal variability in the spontaneous fluctuations of activity and connectivity between amnestic MCI (aMCI) and nonamnestic MCI (naMCI), which enhances the understanding of their different pathophysiologies and provides targets for individualized intervention. METHODS: Sixty-five naMCI and 48 aMCI subjects and 75 healthy controls were recruited. A sliding window analysis was used to evaluate the dynamic amplitude of low-frequency fluctuations (dALFF), dynamic regional homogeneity (dReHo), and dynamic functional connectivity (dFC). The caudal/rostral hippocampus was selected as the seeds for calculating dFC. RESULTS: Both aMCI and naMCI exhibited abnormal dALFF, dReHo, and hippocampal dFC compared with healthy controls. Compared with individuals with naMCI, those with aMCI exhibited (1) higher dALFF variability in the right putamen, left Rolandic operculum, and right middle cingulum, (2) lower dReHo variability in the right superior parietal lobule, and (3) lower dFC variability between the hippocampus and other regions (left superior occipital gyrus, middle frontal gyrus, inferior cerebellum, precuneus, and right superior frontal gyrus). Additionally, variability in dALFF, dReHo, and hippocampal dFC exhibited different associations with cognitive scores in aMCI and naMCI patients, respectively. Finally, dReHo variability in the right superior parietal lobule and dFC variability between the right caudal hippocampus and left inferior cerebellum exhibited partially mediated effects on the different memory scores between people with aMCI and naMCI. CONCLUSION: The aMCI and naMCI patients exhibited shared and specific patterns of dynamic brain activity and connectivity. The dReHo of the superior parietal lobule and dFC of the hippocampus-cerebellum contributed to the memory heterogeneity of MCI subtypes. Analyzing the temporal variability in the spontaneous fluctuations of brain activity and connectivity provided a new perspective for exploring the different pathophysiological mechanisms in MCI subtypes.

A comparison of agreement between actigraphy and polysomnography for assessing sleep during posttraumatic amnesia.

STUDY OBJECTIVES: Sleep disturbance often emerges in the early recovery phase following a moderate to severe traumatic brain injury, known as posttraumatic amnesia. Actigraphy is commonly employed to assess sleep, as it is assumed that patients in posttraumatic amnesia (who display confusion, restlessness, and agitation) would better tolerate this measure over gold-standard polysomnography (PSG). This study evaluated the agreement between PSG and actigraphy for determining (sleep/wake time, sleep efficiency, sleep latency, and awakenings) in patients experiencing posttraumatic amnesia. It also compared the epoch-by-epoch sensitivity, specificity, and accuracy between the Actigraph device's 4 wake threshold settings (low, medium, high, and automatic) to PSG. METHODS: The sample consisted of 24 inpatients recruited from a traumatic brain injury inpatient rehabilitation unit. Ambulatory PSG was recorded overnight at bedside and a Philips Actiwatch was secured to each patient's wrist for the same period. RESULTS: There were poor correlations between PSG and actigraphy for all parameters (Lin's concordance correlation coefficient = < 0.80). The low threshold displayed the highest correlation with PSG for wake and sleep time, albeit still low. Actigraphy displayed low specificity (ranging from 17.1% to 36.6%). There appears to be a greater disparity between actigraphy and PSG for patients with increased wake time. CONCLUSIONS: Actigraphy, while convenient, demonstrated poorer performance in determining sleep-wake parameters in patients with significantly disturbed sleep. Ambulatory PSG can provide a clearer understanding of the extent of sleep disturbances in these patients with reduced mobility during early rehabilitation. Study findings can help design future protocols of sleep assessment during posttraumatic amnesia and optimize treatment. CITATION: Fedele B, McKenzie D, Williams G, Giles R, Olver J. A comparison of agreement between actigraphy and polysomnography for assessing sleep during posttraumatic amnesia. J Clin Sleep Med. 2022;18(11):2605-2616.

Improving Amnesia Diagnostic Accuracy with RAVLT Single Scores and Composite Indices: Italian Normative Data.

OBJECTIVE: The Rey Auditory Verbal Learning Test (RAVLT) is a widely used verbal memory measure that provides scores for different aspects of memory. It involves repeated auditory presentation and recall of a 15-item word list (List A) followed by presentation and recall of a distractor list (List B) and then un-cued immediate and delayed recalls (at 15 min and 1 week) of List A as well as recognition testing. Aims of this study are to provide Italian normative data for certain RAVLT Scores and Composite Indices to improve the diagnostic accuracy of the test in clinical settings and to provide further evidence on how RAVLT can differentiate different amnesia profiles due to focal lesions. METHODS: We enrolled 440 healthy participants and RAVLT Single Scores and Composite Indices have been analyzed by means of multiple regression to verify the influence of age, education, and gender. RESULTS: We computed the best linear models with RAVLT Single Scores and Composite Indices, as dependent variables, and the most suitable transformation of independent variables. By reversing the signs of the regression coefficients, the adjustment factors for each level of age and, if needed, education and gender have been computed and the adjusted scores have been standardized into Equivalent Scores. CONCLUSION: Using these standardized measures, we differentiate three profiles of amnesia due to selective hippocampal sclerosis with severe encoding deficit, fornix lesions with source memory problems, and temporal lobe epilepsy with consolidation failure.

Hippocampal infarction: redefining transient global amnesia.

BACKGROUND AND AIMS: Transient global amnesia (TGA) is a clinical syndrome characterized by sudden anterograde amnesia not accompanied by other neurological symptoms. There is no consensus on the underlying pathophysiological mechanism. However, diffusion-weighted imaging (DWI) of the magnetic resonance imaging (MRI) has demonstrated hippocampal lesions in as many as 50% of cases. This paper describes a series of patients with TGA and hippocampal lesions. METHODS: This study assessed vascular risk factors in patients older than age 18 admitted to the Hospital Universitario San Ignacio, Bogota, Colombia, from May 2017 to June 2020 with a diagnosis of TGA and evidence of hippocampal ischemic lesion on 3 Tesla brain MRI. RESULTS: The authors identified 36 patients, 72.2% female, with mean age 62 years. Cardiovascular risk factors, most frequently high blood pressure, carotid disease, and dyslipidemia, were present in 75% of these patients. Hippocampal lesions were unilateral in 80% of cases, with median size 2.5 mm, most frequently located at the hippocampal body. Approximately 14% of patients also presented acute ischemic lesions in locations other than the hippocampus. CONCLUSIONS: TGA is a clinical entity previously considered to have undetermined etiology. The present study used brain MRI to identify a group of patients with hippocampal ischemic lesions, finding associated vascular risk factors in a high proportion of them.

Time perspective and amnestic mild cognitive impairment.

OBJECTIVE: We examined time perspective in patients with amnesic mild cognitive impairment (aMCI). Prior research has shown that aMCI is associated with difficulties in experiencing time duration and succession. However, this line of inquiry has not been extended to time perspective. We examined associations between aMCI and multiple dimensions of time perspective including perceived orientations and relationships among the past, present, and future. METHOD: Thirty aMCI patients and thirty-three healthy controls participated. Measures were the Time Orientation Scale (TOS), the Time Relation Scale (TRS), and the Zimbardo Time Perspective Inventory (ZTPI), as well as a comprehensive neuropsychological evaluation. RESULTS: The TRS was associated with aMCI. Patients with aMCI were more likely to perceive that time was unrelated than the healthy older adults. Among patients with aMCI, an unrelated time perspective was associated with poorer performance in executive function measures. However, aMCI was not associated with the TOS or the ZTPI. CONCLUSIONS: Patients with aMCI have difficulty in perceiving relationships among the past, present, and future. This could be the consequence of deficits in executive functions. This research suggests that patients with aMCI may have limited understanding for how their current behaviours are related to both their past and future.

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.

Factors Associated With Physical Therapy Engagement During the Period of Posttraumatic Amnesia.

BACKGROUND AND PURPOSE: Physical therapy is important in the management of traumatic brain injury (TBI) and associated multitrauma. Providing therapy during the posttraumatic amnesia (PTA) phase is challenging, given that hallmark features including confusion, amnesia, agitation, and fatigue may impede the person's ability to engage in and benefit from rehabilitation. To date, there is little empirical evidence to guide the provision of therapy during PTA. This observational study aimed to explore the frequency, duration, location, and engagement of physical therapy provision during PTA and the impact of cognition, agitation, and fatigue. SUMMARY OF KEY POINTS: The majority of patients were found to meaningfully engage and participate in physical therapy for the majority of sessions. Only a small proportion were unable to participate in physical therapy. Patient refusal and fatigue were identified as the most prominent barriers to rehabilitation. Despite fatigue and agitation reaching clinical levels, therapy could still successfully proceed on most occasions. RECOMMENDATIONS FOR CLINICAL PRACTICE: Physical therapy is feasible during the acute recovery stages after TBI. Current results support the notion that therapy should commence early to minimize secondary complications and promote the recovery of mobility. A patient-centered therapeutic model that tailors the therapeutic approach to meet the individual's current physical and fluctuating cognitive capabilities may be most suited for this population. Clinicians working with people after TBI need experience in understanding and managing the cognitive limitations and associated symptoms of PTA to optimize the provision of therapy. These findings could inform guidelines for the management of patients in PTA.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A368).

Acute coronary syndrome and transient global amnesia with sumatriptan.

Triptans are potent serotoninergic vasoconstrictors. They are generally avoided in elderly patients age greater than 65 or in patients with a history of CAD. Although there are reported cases of Acute Coronary Syndrome (ACS) or Transient Global Amnesia (TGA) in patients after ingesting therapeutic doses of triptan or dihydroergotamine, this is the first case report, up to our knowledge, of a patient, who had no previous cardiac history, that was diagnosed with both ACS and TGA. A 59-year-old woman with a long-standing history of migraine, gastroesophageal reflux disease, and hypothyroidism, presented to the Emergency Department (ED) complaining of amnesia, chest pain, and left arm numbness after ingesting a single dose of oral sumatriptan approximately 1-2 h prior to arrival. She had no recollection of the events that occurred after taking sumatriptan. No acute laboratory abnormalities were found except for an elevated troponin, which continued to trend upwards. Her EKG had no ST-T wave abnormalities. She was diagnosed with Acute Coronary Syndrome (ACS), non-ST elevation MI. She had a negative noncontrast CT head. Neurology was consulted for her amnesia and diagnosed her with Transient Global Amnesia (TGA). They recommended discontinuing sumatriptan and beginning topiramate as a prophylactic therapy. There is an increasing number of reports delineating sumatriptan's adverse effects. Emergency medicine physicians should promptly recognize the toxic effects and adverse reactions from triptans. Sumatriptan-induced vasoconstriction may lead to cardiac and cerebral ischemic events.

Determining affected memory domains in patients with amnestic mild cognitive impairment using computerized and interactive tests.

This study explores different episodic memory domains, namely object, temporal and spatial memory, affected in patients with a clinical diagnosis of single domain amnestic mild cognitive impairment (aMCI). 15 aMCI patients and 25 healthy controls were recruited and tested. Object, spatial, and temporal memory were tested using computerized tasks and again in interactive, real-world tasks. Controls outperformed patients on the object computerized task and showed a trend toward significance for the computerized spatial and temporal tasks, but there was no difference in spatial and temporal memory when using the interactive tasks, indicating the employment of compensatory mechanisms in patients to overcome some of the memory impairments associated with aMCI. These findings highlight that aMCI patients might delay seeking help due to compensatory mechanisms which mask their deficits in real-world situations.

Association Between Motor Task Performance and Hippocampal Atrophy Across Cognitively Unimpaired, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease Individuals.

Hippocampal atrophy is a widely used biomarker for Alzheimer's disease (AD), but the cost, time, and contraindications associated with magnetic resonance imaging (MRI) limit its use. Recent work has shown that a low-cost upper extremity motor task has potential in identifying AD risk. Fifty-four older adults (15 cognitively unimpaired, 24 amnestic mild cognitive impairment, and 15 AD) completed six motor task trials and a structural MRI. Several measures of motor task performance significantly predicted bilateral hippocampal volume, controlling for age, sex, education, and memory. Thus, this motor task may be an affordable, non-invasive screen for AD risk and progression.

GRK5 Deficiency Causes Mild Cognitive Impairment due to Alzheimer's Disease.

Prevention of Alzheimer's disease (AD) is a high priority mission while searching for a disease modifying therapy for AD, a devastating major public health crisis. Clinical observations have identified a prodromal stage of AD for which the patients have mild cognitive impairment (MCI) though do not yet meet AD diagnostic criteria. As an identifiable transitional stage before the onset of AD, MCI should become the high priority target for AD prevention, assuming successful prevention of MCI and/or its conversion to AD also prevents the subsequent AD. By pulling this string, one demonstrated cause of amnestic MCI appears to be the deficiency of G protein-coupled receptor-5 (GRK5). The most compelling evidence is that GRK5 knockout (GRK5KO) mice naturally develop into aMCI during aging. Moreover, GRK5 deficiency was reported to occur during prodromal stage of AD in CRND8 transgenic mice. When a GRK5KO mouse was crossbred with Tg2576 Swedish amyloid precursor protein transgenic mouse, the resulted double transgenic GAP mice displayed exaggerated behavioral and pathological changes across the spectrum of AD pathogenesis. Therefore, the GRK5 deficiency possesses unique features and advantage to serve as a prophylactic therapeutic target for MCI due to AD.

Τhe Greek Variant in APP Gene: The Phenotypic Spectrum of APP Mutations.

Mutations in the gene encoding amyloid precursor protein (APP) cause autosomal dominant inherited Alzheimer's disease (AD). We present a case of a 68-year-old female who presented with epileptic seizures, neuropsychiatric symptoms and progressive memory decline and was found to carry a novel APP variant, c.2062T>G pLeu688Val. A comprehensive literature review of all reported cases of AD due to APP mutations was performed in PubMed and Web of Science databases. We reviewed 98 studies with a total of 385 cases. The mean age of disease onset was 51.3 ± 8.3 (31-80 years). Mutations were most often located in exons 17 (80.8%) and 16 (12.2%). The most common symptoms were dementia, visuospatial symptoms, aphasia, epilepsy and psychiatric symptoms. Mutations in the ß-amyloid region, and specifically exon 17, were associated with high pathogenicity and a younger age of disease onset. We describe the second reported APP mutation in the Greek population. APP mutations may act variably on disease expression and their phenotype is heterogeneous.

Reduced Thickness of the Anterior Cingulate Cortex as a Predictor of Amnestic-Mild Cognitive Impairment Conversion to Alzheimer's Disease with Psychosis.

BACKGROUND: A long-term follow-up study in patients with amnestic mild cognitive impairment (aMCI) is needed to elucidate the association between regional brain volume and psychopathological mechanisms of Alzheimer's disease with psychosis (AD + P). OBJECTIVE: The purpose of this study was to investigate the effect of the thickness of the angular cingulate cortex (ACC) on the risk of AD + P conversion in patients with aMCI. METHODS: This was a hospital-based prospective longitudinal study including 174 patients with aMCI. The main outcome measure was time-to-progression from aMCI to AD + P. Subregions of the ACC (rostral ACC, rACC; caudal ACC, cACC) and hippocampus (HC) were measured as regions of interest with magnetic resonance imaging and the Freesurfer analysis at baseline. Survival analysis with time to incident AD + P as an event variable was calculated with Cox proportional hazards models using the subregions of the ACC and HC as a continuous variable. RESULTS: Cox proportional hazard analyses showed that the risk of AD + P was associated with sub-regional ACC thickness but not HC volume: reduced cortical thickness of the left cACC (HR [95%CI], 0.224 [0.087-0.575], p = 0.002), right cACC (HR [95%CI], 0.318 [0.132-0.768], p = 0.011). This association of the cACC with the risk of AD also remained significant when adjusted for HC volume. CONCLUSION: We found that reduced cortical thickness of the cACC is a predictor of aMCI conversion to AD + P, independent of HC, suggesting that the ACC plays a vital role in the underlying pathogenesis of AD + P.