Association between antidepressant use and delirium in older adults: an analysis of the World Health Organization's global pharmacovigilance database.

BACKGROUND: Psychoactive drugs frequently cause delirium adverse events in older adults. However, few data on the relationship between antidepressants and delirium are available. Here, we investigated the association between antidepressant prescription and pharmacovigilance reports of delirium in older adults. METHODS: Using the World Health Organization's VigiBase® global pharmacovigilance database from 1967 to 2022, we performed a disproportionality analysis in order to probe the putative associations between each antidepressant class (non-selective monoamine reuptake inhibitors (NSMRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), alpha-2-adrenergic receptor antagonists, and other antidepressants) and reports of delirium in people aged 65 or over. We calculated the reporting odds ratios (r-OR) and their 95% confidence interval ([95%CI]) with logistic regression models before and after adjustment for confounding factors. Secondary analyses were performed for each drug and within each class by age group (65-74, and 75 and over). We also studied the reports of concomitant delirium and hyponatremia. RESULTS: Our main analysis included 87,524 cases of delirium. After adjustment for confounders, a significant association was found between delirium and all antidepressant classes other than SNRIs. Intraclass disparities were found for the association between the most frequently prescribed antidepressants and reports of delirium. An elevated risk of reports of concomitant delirium and hyponatremia was found for SSRIs (4.46 [4.01-4.96]), SNRIs (1.25 [1.07-1.46]), MAOIs (1.72 [1.41-2.09]), and the "other antidepressants" class (1.47 [1.30-1.65]). CONCLUSIONS: There was a significant association between reports of delirium and antidepressant classes (other than SNRIs). However, this association varied from one drug to another within a given antidepressant class. Moreover, this association could not always be explained by antidepressant-induced hyponatremia.

Evaluation of the cognitive outcome after out-of-hospital cardiac arrest: The role of thalamus.

Cardiac arrest survivors develop a variety of neuropsychological impairments and neuroanatomical lesions. The goal of this study is to evaluate if brain voxel-based morphometry and lesional Magnetic Resonance Imaging (MRI) analyses performed in the acute phase of an Out-of-Hospital Cardiac Arrest (OHCA) can be sensitive enough to predict the persistence of neuropsychological disorders beyond 3 months. Survivors underwent a prospective brain MRI during the first month after an OHCA and performed neuropsychological assessments at 1 and 3 months. According to the second neuropsychological assessment, survivors were separated into two subgroups, a deficit subgroup with persistent memory, executive functions, attention and/or praxis disorders (n = 11) and a preserved subgroup, disorders free (n = 14). Brain vascular lesion images were investigated, and volumetric changes were compared with healthy controls. Correlations were discussed between brain MRI results, OHCA data and the second neuropsychological assessment. Analyses of acute ischemic lesions did not reveal significant differences between the two subgroups (p = .35), and correlations with cognitive impairments could not be assessed. voxel-based morphometry analyses revealed a global cerebral volume reduction for the two subgroups and a clear decrease of the right thalamic volume for the deficit subgroup. It was associated with a cognitive dysexecutive syndrome represented by four executive indexes according to the 'Groupe de Réflexion pour l'Evaluation des Fonctions EXécutives' criteria. The right thalamus atrophy seems to be more predictive than the vascular lesions and more specific than a global cerebral volume reduction of post-OHCA neuropsychological executive disorders.

Looking beyond the face area: lesion network mapping of prosopagnosia.

Damage to the right fusiform face area can disrupt the ability to recognize faces, a classic example of how damage to a specialized brain region can disrupt a specialized brain function. However, similar symptoms can arise from damage to other brain regions, and face recognition is now thought to depend on a distributed brain network. The extent of this network and which regions are critical for facial recognition remains unclear. Here, we derive this network empirically based on lesion locations causing clinically significant impairments in facial recognition. Cases of acquired prosopagnosia were identified through a systematic literature search and lesion locations were mapped to a common brain atlas. The network of brain regions connected to each lesion location was identified using resting state functional connectivity from healthy participants (n = 1000), a technique termed lesion network mapping. Lesion networks were overlapped to identify connections common to lesions causing prosopagnosia. Reproducibility was assessed using split-half replication. Specificity was assessed through comparison with non-specific control lesions (n = 135) and with control lesions associated with symptoms other than prosopagnosia (n = 155). Finally, we tested whether our facial recognition network derived from clinically evident cases of prosopagnosia could predict subclinical facial agnosia in an independent lesion cohort (n = 31). Our systematic literature search identified 44 lesions causing prosopagnosia, only 29 of which intersected the right fusiform face area. However, all 44 lesion locations fell within a single brain network defined by connectivity to the right fusiform face area. Less consistent connectivity was found to other face-selective regions. Surprisingly, all 44 lesion locations were also functionally connected, through negative correlation, with regions in the left frontal cortex. This connectivity pattern was highly reproducible and specific to lesions causing prosopagnosia. Positive connectivity to the right fusiform face area and negative connectivity to left frontal regions were independent predictors of prosopagnosia and predicted subclinical facial agnosia in an independent lesion cohort. We conclude that lesions causing prosopagnosia localize to a single functionally connected brain network defined by connectivity to the right fusiform face area and to left frontal regions. Implications of these findings for models of facial recognition deficits are discussed.

Acute loss of psychic self-activation after cardiac arrest and delayed bilateral pallidal lesions on brain MRI.

The delay between cardiac arrest and brain MRI is usually extremely different in the few cerebral imaging studies assessing the affected brain areas. We report an unusual case of loss of psychic self-activation appeared immediately after a cardiac arrest in a middle age patient. The first brain MRI, one month after the vascular event, did not show the classical lesions typically reported, such as lesion of the caudate nucleus or the globus pallidus. Two years later, although the cognitive performances of our patient were improved, a second brain MRI demonstrated bilateral pallidal lesions, suggesting a possible mechanism with delayed hypoxic lesions.

Imaging Characteristics of Venous Parenchymal Abnormalities.

BACKGROUND AND PURPOSE: There are few published data on the patterns of parenchymal imaging abnormalities in a context of cerebral venous thrombosis (CVT). The objectives of the present study were to describe the patterns of parenchymal lesions associated with CVT and to determine the lesion sites. METHODS: We included 44 consecutively hospitalized patients with CVT and parenchymal lesions on magnetic resonance imaging. The diagnosis of CVT had been confirmed by magnetic resonance imaging/magnetic resonance venography. Magnetic resonance imaging patterns for CVT were retrospectively analyzed with regard to the lesion's type, shape, and site. RESULTS: The most frequent stroke subtype was hemorrhagic ischemia (in 56.8% of cases), followed by intracerebral hematoma (in 22.72% of cases) and nonhemorrhagic ischemia (in 20.45% of cases). Although there were no significant differences between these 3 groups with regard to the clinical and radiological characteristics, we observed a nonsignificant trend (P=0.08) toward a shorter time interval between hospital admission and magnetic resonance imaging for nonhemorrhagic stroke. The CVT parenchymal abnormalities were centered on 6 main foci and were related to the site of venous occlusion: (1) the inferior parietal lobule (n=20; 44.5%), associated mainly with occlusion of the transverse sinus (n=10) or pure cortical veins (n=10); (2) the inferior and posterior temporal regions (n=10; 22.75%), associated mainly with occlusion of the transverse sinus (n=9); (3) the parasagittal frontal region (n=6; 13.6%), associated mainly with occlusion of the superior sagittal sinus (n=4) or the transverse sinus (n=4); (4) the thalamus (n=5; 11.3%) associated with occlusion of the straight sinus (n=5); (5) the cerebellar hemisphere (n=2; 4.5%), associated in both cases with occlusion of the transverse sinus; and (6) the deep hemispheric regions (n=3; 6.8%), associated with occlusion of the superior sagittal sinus in all cases. CONCLUSIONS: Parenchymal lesions caused by CVT display specific anatomic patterns, which is mainly determined by the site of venous occlusion.

APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases.

BACKGROUND: Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. METHODS AND FINDINGS: We report here a novel update (2012-2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers-total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid ß (Aß)42-in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. CONCLUSIONS: Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole sample of families and isolated cases, definite pathogenicity is currently established for only 77%, emphasizing the need to pursue the effort to classify variants.

Cross-validation of a Shortened Battery for the Assessment of Dysexecutive Disorders in Alzheimer Disease.

The frequency of executive disorders in mild-to-moderate Alzheimer disease (AD) has been demonstrated by the application of a comprehensive battery. The present study analyzed data from 2 recent multicenter studies based on the same executive battery. The objective was to derive a shortened battery by using the GREFEX population as a training dataset and by cross-validating the results in the REFLEX population. A total of 102 AD patients of the GREFEX study (MMSE=23.2±2.9) and 72 patients of the REFLEX study (MMSE=20.8±3.5) were included. Tests were selected and receiver operating characteristic curves were generated relative to the performance of 780 controls from the GREFEX study. Stepwise logistic regression identified 3 cognitive tests (Six Elements Task, categorical fluency and Trail Making Test B error) and behavioral disorders globally referred as global hypoactivity (P=0.0001, all). This shortened battery was as accurate as the entire GREFEX battery in diagnosing dysexecutive disorders in both training group and the validation group. Bootstrap procedure confirmed the stability of AUC. A shortened battery based on 3 cognitive tests and 3 behavioral domains provides a high diagnosis accuracy of executive disorders in mild-to-moderate AD.

Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification.

Idiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: <40, 40-60, and >60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis revealed that the total calcification scores correlated positively with age in controls and patients, but increased more rapidly with age in patients. The expected total calcification score was greater in SLC20A2 than PDGFRB mutation carriers, beyond the effect of the age alone. No patient with a PDGFRB mutation exhibited a cortical or a vermis calcification. The total calcification score was more severe in symptomatic versus asymptomatic individuals. We provide the first phenotypical description of a case series of patients with idiopathic basal ganglia calcification since the identification of the first causative genes. Clinical and radiological diversity is confirmed, whatever the genetic status. Quantification of calcification is correlated with the symptomatic status, but the location and the severity of the calcifications don't reflect the whole clinical diversity. Other biomarkers may be helpful in better predicting clinical expression.

MEM&SO protocol: understanding the determinants of social learning in neurodegenerative diseases.

BACKGROUND: People with neurodegenerative diseases may have difficulty learning new information, owing to their cognitive impairments. Teaching them techniques for learning in social contexts could alleviate this difficulty. The present study will examine the performances of patients with Alzheimer's disease and patients with the semantic variant of primary progressive aphasia on a memory test administered in three social contexts. The protocol will make it possible to identify determinants of social interactions, social abilities, cognition, and personality that can explain the potentially beneficial effect of social context on learning in these patients. METHODS: Thirty dyads (patient with primary memory impairment who meets criteria for Alzheimer's disease paired with caregiver), 16 dyads (patient meeting criteria for semantic variant of primary progressive aphasia paired with caregiver), and 46 dyads (healthy controls with no cognitive complaints) will be recruited. A nonverbal memory test (social memory task) will be administered to each dyad in three different social contexts (presence-only, observation, collaboration). Patients and healthy controls will also undergo a neuropsychological assessment to measure social (interactions and abilities), cognitive and personality aspects. Patients will be compared with controls on differential social scores calculated between the presence-only and collaboration contexts, and between the presence-only and observation contexts. A multiple comparative case study will be conducted to identify social, cognitive and personality variables that potentially explain the differential scores in the collaboration and observation contexts. DISCUSSION: For the first time, memory will be assessed in patients with Alzheimer's disease and patients with the semantic variant of primary progressive aphasia in three different contexts (presence-only, observation, collaboration). The multiple comparative case study will make it possible to identify the determinants of memory performance in the social context, in order to create the most beneficial learning context for individual patients, according to their profile. TRIAL REGISTRATION: This study was approved by the Ile de France XI institutional review board (2022-A00198-35), and registered on ClinicalTrials.gov (no. NCT05800028), on April 27, 2023.

Cerebrospinal Fluid Profile of Tau, Phosphorylated Tau, Aß42, and Aß40 in Probable Cerebral Amyloid Angiopathy.

BACKGROUND: There is no consensus regarding the diagnostic value of cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in cerebral amyloid angiopathy (CAA). OBJECTIVE: To describe the CSF levels of Aß42, Aß40, total protein Tau, and phosphorylated-Tau (p-Tau) in a large series of probable CAA patients and to compare with AD patients in order to identify a specific pattern in CAA but also to look for correlations with the neuroimaging profile. METHODS: We retrospectively included from 2 French centers probable CAA patients according to modified Boston criteria who underwent lumbar puncture (LP) with CSF AD biomarker quantifications. Two neurologists independently analyzed all MRI sequences. A logistic regression and Spearman's correlation coefficient were used to identify correlation between MRI and CSF biomarkers in CAA. RESULTS: We included 63 probable CAA and 27 AD patients. Among CAA 50.8% presented with decreased Aß42 level associated with elevated p-Tau and/or Tau, 34.9% with isolated decreased Aß42 level and 14.3% patients with normal Aß42 level. Compared to AD, CAA showed lower levels of Tau (p = 0.008), p-Tau (p = 0.004), and Aß40 (p = 0.001) but similar Aß42 level (p = 0.07). No correlation between Aß42 or Aß40 levels and neuroimaging was found. CONCLUSION: CSF biomarkers may improve the accuracy of the modified Boston criteria with altered profile in 85% of the patients fulfilling revised Boston criteria for probable CAA. Aß40 appears as an interesting selective biomarker in differential diagnosis.

Telemedicine in French Memory Clinics During the COVID-19 Pandemic.

This multicenter study was conducted in French memory clinics during the first COVID-2019 lockdown (March-May 2020). The objective was to evaluate the effect of a telemedicine consultation on treatment modification in dementia care. Among 874 patients who had a telemedicine consultation, 103 (10.7%) had treatment modifications, in particular those living with a relative or diagnosed with Alzheimer's disease. A control group of patients referred March-May 2019 was also included. Treatment modification rate was similar between periods with an adjusted percentage difference of -4% (p = 0.27). Telemedicine consultations allowed treatment modifications with only a minor short-term negative impact on therapeutic strategies.

Can we remember future actions yet forget the last two minutes? Study in transient global amnesia.

Transient global amnesia (TGA) is a clinical syndrome characterized by the abrupt onset of a massive episodic memory deficit that spares other cognitive functions. If the anterograde dimension is known to be impaired in TGA, researchers have yet to investigate prospective memory (PM)--which involves remembering to perform an intended action at some point in the future--in this syndrome. Furthermore, as executive functions are thought to be spared in this syndrome, TGA provides an opportunity to examine the impact of a massive "pure" memory impairment on PM. We assessed 38 patients with a newly designed protocol that distinguished between the prospective (remembering to do something at the appropriate time) and retrospective (remembering what has to be done) components of PM. Moreover, we investigated episodic memory with an anterograde memory task and assessed executive functions, anxiety and mood, as well as their links with PM. We demonstrated that PM is impaired during TGA, with a greater deficit for the retrospective component than for the prospective component. Furthermore, we highlighted a strong link between these two components. Anterograde episodic memory impairments were correlated with retrospective component deficits in TGA patients, although we were able to confirm that executive functions are globally spared. We discuss this pattern of results within the theoretical framework of PM, putting forward new arguments in favor of the idea that PM deficits can occur mainly because of a massive anterograde memory deficit. The clinical consequences of PM impairment in TGA are examined.

Early onset dementia: characteristics in a large cohort from academic memory clinics.

AIM: To describe the characteristics of early-onset dementia (EOD) in a cohort from 3 memory clinics. METHODS: We assessed all patients with dementia referred to the Academic Memory Clinics at Amiens, Lille, and Rouen University Medical Centers between 2005 and 2007. Patients aged less than 65 years at the time of onset of symptom were included in the EOD group, whereas older patients were included in the late-onset dementia (LOD) group. RESULTS: Three thousand four hundred and seventy-three patients (including 1932 women) were included and 811 (23.4%) were classified as EOD. The sex ratio was 1.12, whereas women were overrepresented in LOD (P=0.001). Patients with EOD were more frequently (P=0.001) living at home (87.3%), they had a lower educational level than the general population (P=0.0001) but were more educated (P=0.001). The current Mini Mental State Examination did not differ (P=0.3) between EOD (18.6±7.6) and LOD (18.9±6). The most common causes of EOD were Alzheimer's (22.3%) and vascular (15.9%) diseases and 4 pathologies that were significantly more frequent (P=0.001) than in the LOD group: frontotemporal dementia (9.7%), alcohol-related dementia (9.4%), traumatic brain injury (3.8%), and Huntington's disease (3%). CONCLUSIONS: EOD is characterized by specific features and different causes although Alzheimer's and vascular dementias remain the main causes of dementia in EOD.

[Neurodevelopmental disorders modify neurodegenerative diseases: a medical history to screen in memory clinic]. / Les troubles neurodéveloppementaux miment ou influencent les pathologies neurodégénératives : prise en compte des antécédents neurodéveloppementaux en consultation mémoire.

Neurodevelopmental disorders are frequent in the general population and are often lifelong conditions despite sometimes being masked by conscious or unconscious compensation and avoidance mechanisms. These conditions are often unknown or underestimated in adults, even when diagnosed in childhood. Neurodevelopmental disorders share similarities with and frequently interact in a complex way with neurodegenerative disorders. Considering these aspects during memory clinic assessments can provide a new perspective on lifelong neurocognitive trajectories. Assessing both neurodevelopmental and neurodegenerative dimensions is challenging but should improve diagnostic accuracy. It is therefore necessary to understand the lifelong specific neurocognitive trajectory of each patient in order to develop personalized and focused cognitive medicine and care.

Nucleus Basalis of Meynert Stimulation for Lewy Body Dementia: A Phase I Randomized Clinical Trial.

OBJECTIVES: Nucleus basalis of Meynert deep brain stimulation (NBM-DBS) has been proposed for patients with dementia. Here, we aim to assess the safety and effects of NBM-DBS in patients with Lewy body dementia (LBD), in a randomized, double-blind, crossover clinical trial. METHODS: Six patients with mild to moderate LBD (mean [SD] age, 62.2 [7.8] years) were included, operated on for bilateral NBM-DBS, and assigned to receive either active or sham NBM-DBS followed by the opposite condition for 3 months. The primary outcome was the difference in the total free recalls of the Free and Cued Selective Reminding Test (FCSRT) between active and sham NBM-DBS. Secondary outcomes were assessments of the safety and effects of NBM-DBS on cognition, motor disability, sleep, and PET imaging. RESULTS: There was no significant difference in the FCSRT score with active vs sham NBM-DBS. The surgical procedures were well tolerated in all patients, but we observed significant decreases in Stroop and Benton scores after electrode implantation. We observed no significant difference in other scales between active and sham NBM-DBS. With active NBM-DBS relative to baseline, phonemic fluency and motor disability significantly decreased. Lastly, the superior lingual gyrus metabolic activity significantly increased with active NBM-DBS. CONCLUSIONS: NBM-DBS does not appear to be totally safe for patients with LBD with no evidence of cognitive benefit. CLINICALTRIALSGOV IDENTIFIER: NCT01340001. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, for patients with LBD operated on for bilateral NBM-DBS, active NBM-DBS stimulation compared to sham stimulation did not significantly change selective recall scores.

Primary Progressive Aphasia Associated With GRN Mutations: New Insights Into the Nonamyloid Logopenic Variant.

OBJECTIVE: To determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with GRN (progranulin) mutations and to study their neuroanatomic correlates. METHODS: Patients with PPA carrying GRN mutations (PPA-GRN) were selected among a national prospective research cohort of 1,696 patients with frontotemporal dementia, including 235 patients with PPA. All patients with amyloid-positive CSF biomarkers were excluded. In this cross-sectional study, speech/language and cognitive profiles were characterized with standardized evaluations, and gray matter (GM) atrophy patterns using voxel-based morphometry. Comparisons were performed with controls and patients with sporadic PPA. RESULTS: Among the 235 patients with PPA, 45 (19%) carried GRN mutations, and we studied 32 of these. We showed that logopenic PPA (lvPPA) was the most frequent linguistic variant (n = 13, 41%), followed by nonfluent/agrammatic (nfvPPA; n = 9, 28%) and mixed forms (n = 8, 25%). Semantic variant was rather rare (n = 2, 6%). Patients with lvPPA, qualified as nonamyloid lvPPA, presented canonical logopenic deficit. Seven of 13 had a pure form; 6 showed subtle additional linguistic deficits not fitting criteria for mixed PPA and hence were labeled as logopenic-spectrum variant. GM atrophy involved primarily left posterior temporal gyrus, mirroring neuroanatomic changes of amyloid-positive-lvPPA. Patients with nfvPPA presented agrammatism (89%) rather than apraxia of speech (11%). CONCLUSIONS: This study shows that the most frequent PPA variant associated with GRN mutations is nonamyloid lvPPA, preceding nfvPPA and mixed forms, and illustrates that the language network may be affected at different levels. GRN testing is indicated for patients with PPA, whether familial or sporadic. This finding is important for upcoming GRN gene-specific therapies.

Morbid risk for schizophrenia in first-degree relatives of people with frontotemporal dementia.

BACKGROUND: Familial co-occurrence of frontotemporal dementia and schizophrenia has never been investigated. AIMS: To test the hypothesis that frontotemporal dementia and schizophrenia might have a common aetiology in some families in which both syndromes coexist (mixed families). METHOD: The morbid risk for schizophrenia, calculated in first-degree relatives of 100 frontotemporal dementia probands, was compared with that calculated in first-degree relatives of 100 Alzheimer's disease probands. In mixed families, sequencing analysis of known frontotemporal dementia genes and detailed phenotype characterisation of individuals with frontotemporal dementia and schizophrenia were performed. RESULTS: The morbid risk for schizophrenia was significantly higher in relatives of frontotemporal dementia probands (1.35, s.e. = 0.45) than in relatives of Alzheimer's disease probands (0.32, s.e. = 0.22). Ten mixed families were characterised. In three of them a frontotemporal dementia causal mutation was identified that was present in individuals with schizophrenia. Several specific clinical features were noted in people with schizophrenia and frontotemporal dementia in mixed families. CONCLUSIONS: Co-occurrence of schizophrenia and frontotemporal dementia could indicate, in some families, a common aetiology for both conditions.

Retrograde amnesia with transposition in the past: A neuropsychological and PET study of a case.

OBJECTIVE: Retrograde amnesia (RA) with a "transposition in the past" phenomenon has been rarely reported. Patients presenting disproportionate RA for all events over a defined period of time offer an opportunity to investigate the unclear relationship between autobiographical memory and the self, through the well-known self-memory system (SMS). METHOD: We report the case of a 31-year-old right-handed woman who presented to the emergency department of our tertiary care center with an ongoing episode of RA. After resolution of the episode, she had a second transient episode of RA. An extensive neuropsychological battery was performed to assess her autobiographical and nonautobiographical memory during and after the 2 episodes of RA. She also had an 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG PET) scan during the second RA episode. RESULTS: During the 2 RA episodes, results showed lacunar amnesia for autobiographical as well as nonautobiographical memories of the time period between the present and the past 15 years, with preserved anterograde memory. Moreover, her memories before this lost period were more accurate than those after the 2 RA episodes. During the 2 RA episodes, our patient experienced a "transposition in the past" phenomenon. Statistical analysis of the PET scan demonstrated a significant hypometabolism within the right hippocampus. CONCLUSION: The "transposition in the past" phenomenon illustrates the relationship between both episodic and autobiographical memories and the functioning of self, according to the SMS model. Moreover, this case suggests the involvement of the hippocampus in this phenomenon. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Relevant category-specific effect on naming in Alzheimer's disease.

AIM: To determine category effect on naming in Alzheimer's disease (AD) and its relation with severity of the disease or naming deficit. METHODS: A group of 50 patients suffering from probable AD was tested in a naming task involving 99 pictures of items belonging to living and non-living categories. Parameters relating to pictures (percentage of majority responses, familiarity, visual complexity and image agreement) were determined using a control group and parameters relating to words (frequency, age of acquisition, number of letters and syllables) were controlled. RESULTS: A category-specific effect was demonstrated and individual stepwise logistic regression demonstrated a significant category effect in 9 cases (living items more failed than non-living). CONCLUSION: Our results suggest a categorical effect on naming in favor of the non-living items, especially for mild AD with predominant naming deficit.