Search

Young‐onset dementia comprises a heterogeneous range of dementias, with onset at less than 65 years of age. These include primary dementias such as Alzheimer disease, frontotemporal and vascular dementias; genetic/familial dementias; metabolic disorders; and secondary dementias such as those that result from alcohol use disorder, traumatic brain injury, and infections.The presentation of young‐onset dementia is varied and may include cognitive, psychiatric and neurological symptoms. Diagnostic delay is common, with a frequent diagnostic conundrum being, “Is this young‐onset dementia or is this psychiatric?”.For assessment and accurate diagnosis, a thorough screen is recommended, such as collateral history and investigations such as neuroimaging, lumbar puncture, neuropsychology, and genetic testing.The management of young‐onset dementia needs to be age‐appropriate and multidisciplinary, with timely access to services and consideration of the family (including children).

Differences in bulimic and impulsive behaviours in Eating Disorders (ED) have been associated with cortico-striatal circuit dysfunction at a neurobiological level. We sought to investigate neo-striatal volume as a biomarker in ED subgroups as well as the possible relationship with trauma history.

Objective: Previous investigation has revealed stable olfactory identification deficits in neuroleptic-naive patients experiencing a first episode of psychosis, but it is unknown if these deficits predate illness onset. Method: The olfactory identification ability of 81 patients at ultra-high risk for psychosis was examined in relation to that of 31 healthy comparison subjects. Twenty-two of the ultra-high-risk patients (27.2%) later became psychotic, and 12 of these were diagnosed with a schizophrenia spectrum disorder. Results: There was a significant impairment in olfactory identification ability in the ultra-high-risk group that later developed a schizophrenia spectrum disorder but not in any other group. Conclusions: These findings suggest that impairment of olfactory identification is a premorbid marker of transition to schizophrenia, but it is not predictive of psychotic illness more generally.

BackgroundIn the clinical setting, identification of the genetic cause in patients with early-onset dementia (EOD) is challenging due to multiple types of genetic tests required to arrive at a diagnosis. Whole-genome sequencing (WGS) has the potential to serve as a single diagnostic platform, due to its superior ability to detect common, rare and structural genetic variation.MethodsWGS analysis was performed in 50 patients with EOD. Point mutations, small insertions/deletions, as well as structural variants (SVs) and short tandem repeats (STRs), were analysed. An Alzheimer’s disease (AD)-related polygenic risk score (PRS) was calculated in patients with AD.ResultsClinical genetic diagnosis was achieved in 7 of 50 (14%) of the patients, with a further 8 patients (16%) found to have established risk factors which may have contributed to their EOD. Two pathogenic variants were identified through SV analysis. No expanded STRs were found in this study cohort, but a blinded analysis with a positive control identified a C9orf72expansion accurately. Approximately 37% (7 of 19) of patients with AD had a PRS equivalent to >90th percentile risk.DiscussionWGS acts as a single genetic test to identify different types of clinically relevant genetic variations in patients with EOD. WGS, if used as a first-line clinical diagnostic test, has the potential to increase the diagnostic yield and reduce time to diagnosis for EOD.

Objective: The authors used single-subject functional imaging analyses to 1) corroborate the findings of anterior cingulate hypoperfusion during an attentional task in schizophrenia and 2) examine whether anterior cingulate activation is associated with underlying morphology. Method: Five healthy subjects and six patients with schizophrenia underwent positron emission tomography scanning while they performed the Stroop task. The medial-frontal lobes were masked out for analysis, and activation peaks were individually coregistered to each subject's magnetic resonance imaging scan. Results: Healthy subjects showed activations in both limbic and paralimbic anterior cingulate regions. Patients with schizophrenia showed only paralimbic activations, and these were apparent only in patients having a paracingulate sulcus. Conclusions: These findings suggest that 1) patients with schizophrenia have limbic-anterior cingulate hypoperfusion during attentional tasks and 2) paralimbic activation is associated with underlying morphology. (Am J Psychiatry 2002; 159:251-254)

Background: Anorexia nervosa (AN) is a potentially fatal psychiatric condition, associated with structural brain changes such as gray matter volume loss. The pathophysiological mechanisms for these changes are not yet fully understood. Iron is a crucial element in the development and function of the brain. Considering the systemic alterations in iron homeostasis in AN, we hypothesized that brain iron would be altered as a possible factor associated with structural brain changes in AN. Methods: In this study, we used quantitative susceptibility mapping (QSM) magnetic resonance imaging to investigate brain iron in current AN (c-AN) and weight-restored AN compared with healthy individuals. Whole-brain voxel wise comparison was used to probe areas with possible group differences. Further, the thalamus, caudate nucleus, putamen, nucleus accumbens, hippocampus, and amygdala were selected as the regions of interest (ROIs) for ROI-based comparison of mean QSM values. Results: Whole-brain voxel-wise and ROI-based comparison of QSM did not reveal any differences between groups. Exploratory analyses revealed a correlation between higher regional QSM (higher iron) and lower body mass index, higher illness severity, longer illness duration, and younger age at onset in the c-AN group. Conclusions: This study did not find evidence of altered brain iron in AN compared to healthy individuals. However, the correlations between clinical variables and QSM suggest a link between brain iron and weight status or biological processes in AN, which warrants further investigation.

Physical comorbidity may account for some of the pre-mature deaths of people with schizophrenia. It is important to recognize and manage morbidity in people with schizophrenia, as an improvement in the detection and treatment of medical illness will be beneficial for the psychosocial functioning and improving the quality of life of people with schizophrenia.

ObjectivePsychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research.MethodsIn this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP).ResultsCompared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups.ConclusionPosterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy.

Objective: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recentonset psychosis, the majority of whom were neuroleptic naive. Method: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of who had not received antipsychotic medication, were compared to 38 age -- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. Results: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after controlling for gender, premorbid or current IQ, smoking history, cannabis use, or the effects of medication. Diagnostic subgroups did not differ in olfactory identification ability. The deficits remained stable at 6-month follow-up and were associated with negative symptoms at both time points. No relationship was found between olfactory identification ability and length of either untreated psychosis or illness prodrome. Conclusions: Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms. (Am J Psychiatry 2001; 158:107-115)

Sarcoidosis is a multisystem granulomatous inflammatory disorder. A patient having sarcoidosis with Cryptococcal dementia is examined and it is observed that sarcoidosis is associated with an increased risk of infection with Cryptococcus species, independent of immunosuppression and Cryptococcal meningitis is a treatable and reversible cause of dementia.

OBJECTIVE To determine whether patients who fail their first antiepileptic drug (AED) have better neuropsychiatric and quality-of-life (QOL) outcomes if substituted to levetiracetam monotherapy compared with a second older AED. DESIGN Randomized comparative trial. Participants with partial epilepsy who had failed monotherapy with phenytoin sodium, carbamazepine, or valproate sodium were randomized to substitution monotherapy with levetiracetam or a different older AED. Assessments were performed at baseline, 3 months, and 12 months using questionnaires measuring neuropsychiatric, QOL, seizure control, AED adverse effects, and neurocognitive outcomes. SETTING Epilepsy service of a teaching hospital. PATIENTS Fifty-one patients were randomized to levetiracetam and 48 were randomized to a second older AED (25 to valproate and 23 to carbamazepine). MAIN OUTCOME MEASURES Proportions showing improvements in depression (on the Hospital Anxiety and Depression Scale) and QOL scores (on the 89-item Quality of Life in Epilepsy Inventory) at 3 months. RESULTS There were no differences between the groups in depression scores at 3 months (improvement in 17 of 43 patients [39.5%] in the levetiracetam group and 15 of 44 patients [34.1%] in the older AED group; P = .60), but a greater proportion of the older AED group improved on the 89-item Quality of Life in Epilepsy Inventory compared with the levetiracetam group (27 of 38 patients [71.1%] vs 21 of 43 patients [48.8%], respectively; P = .04). The QOL, anxiety, and AED adverse effects scores were improved in both groups at 3 and 12 months after randomization. CONCLUSIONS Substitution monotherapy in a patient experiencing ongoing seizures or tolerability issues is associated with sustained improvements in measures of QOL, psychiatric, and adverse events outcomes. Patients switched to levetiracetam do not have better outcomes than those switched to a second older AED. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12606000102572

Objectives: To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis. Methods: Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy (1H-MRS) measurements were performed prior to initiation and following three months of treatment in 11 UHR patients receiving low-dose lithium and 10 UHR patients receiving treatment as usual (TAU). HT2RT and 1H-MRS percentage change scores between scans were compared using repeated measures ANOVA and correlated with behavioural change scores. Results: Low-dose lithium significantly reduced HT2RT compared to TAU (p0.018). No significant group by time effects was seen for any brain metabolites as measured with 1H-MRS, although myo-inositol, creatine, choline-containing compounds and NAA increased in the group receiving low-dose lithium and decreased or remained unchanged in subjects receiving TAU. Conclusions: This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder.

To examine baseline clinical features of psychogenic nonepileptic seizures (PNES) in a large cohort and to investigate outcome over a period of up to 10 years. Studies investigating PNES have been limited by differences in diagnostic criteria, short follow-up periods, and the use of limited outcome measures.

ABSTRACTBackground:While the adult form of adrenoleukodystrophy (ALD) has been associated with an elevated rate of affective disturbance, the myeloneuropathic form of the disease known as adrenomyeloneuropathy (AMN) has been associated with only occasional cases of major mental illness. Given that cerebral involvement occurs in up to half of AMN sufferers, we hypothesized that rates of mental illness may match those with adult ALD.Objective:To describe the psychiatric, cognitive, and disability variables in a sample of Australian AMN sufferers.Methods:Ten genetically confirmed AMN sufferers underwent diagnostic psychiatric interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth EditionAxis I Disorders), rating scales of psychiatric disturbance (Brief Psychiatric Rating Scale, Hospital Anxiety and Depression Scale, Beck Depression and Anxiety Inventories, and Short-Form 36), and cognitive function (the Neuropsychiatry Unit Cognitive Assessment Tool and Mini-Mental State Examination).Results:While the group as a whole was generally cognitively intact, it demonstrated a higher than expected prevalence of lifetime and current major affective illness. Current symptom levels were low at the time of study participation. Psychopathology did not relate to adrenal status, nor to level of physical or functional impairment.Conclusion:This small sample suggests that the level of psychiatric morbidity in AMN patients is elevated, and the rate of affective disturbance approaches those of adult ALD sufferers. This may reflect that AMN is not a “pure” myeloneuropathy, and that mild cerebral involvement may be associated with affective illness.

Anomalies of movement are observed both clinically and experimentally in schizophrenia. While the basal ganglia have been implicated in its pathogenesis, the nature of such involvement is equivocal. The basal ganglia may be involved in bimanual coordination through their input to the supplementary motor area (SMA). While a neglected area of study in schizophrenia, a bimanual movement task may provide a means of assessing the functional integrity of the motor circuit. Twelve patients with chronic schizophrenia and 12 matched control participants performed a bimanual movement task on a set of vertically mounted cranks at different speeds (1 and 2 Hz) and phase relationships. Participants performed in-phase movements (hands separated by 0°) and out-of-phase movements (hands separated by 180°) at both speeds with an external cue on or off. All participants performed the in-phase movements well, irrespective of speed or cueing conditions. Patients with schizophrenia were unable to perform the out-of-phase movements, particularly at the faster speed, reverting instead to the in-phase movement. There was no effect of external cueing on any of the movement conditions. These results suggest a specific problem of bimanual coordination indicative of SMA dysfunction per se and/or faulty callosal integration. A disturbance in the ability to switch attention during the out-of-phase task may also be involved.

The accuracy and efficiency of protocols to measure intracranial volume (ICV) from volumetric magnetic resonance imaging (MRI) studies has not been formally analyzed. The ICV of 30 control participants was obtained by tracing every slice of a MRI dataset on which the cranial cavity appeared, and compared with estimated ICVs calculated by progressively selecting one of every xslices (i.e., “1‐in‐x”) as a sampling strategy. The reliability and precision of each sampling strategy was then determined. There was virtually no reduction in reliability at the 1‐in‐10 sampling strategy, with a reliability exceeding 0.999. ICV can be confidently traced using a 1‐in‐10 sampling strategy, which should result in significant time savings. Magn Reson Med 44:973–977, 2000. © 2000 Wiley‐Liss, Inc.

Objectives: Functional imaging technologies allow assessment of cerebral blood flow, cerebral metabolism, cellular metabolic processes, cerebral receptor density and occupancy. This review examines the contribution of such studies to our understanding of schizophrenia. The role of the frontal lobes, the basal ganglia, the temporal lobes and the neuronal circuits which connect them is examined with respect to this literature.Method: All studies in schizophrenia using positron emission tomography, single photon emission computerised tomography, xenon studies, functional and spectroscopic magnetic resonance imaging formed the basis of this review. Only those studies published in English were reviewed.Results: The most consistent finding in schizophrenia has been that of hypofrontality, while the results of studies examining subcortical structures provide preliminary support for the concept of fronto-striatal dysfunction. Functional imaging has not yet provided consistent results in the study of temporal lobe function. Although receptor studies have shed light on the actions of antipsychotic medications, the findings for dopamine receptor numbers remain controversial. Spectroscopic and functional MRI remain in their infancy as research tools in schizophrenia.Conclusions: Although there are significant methodological issues to be addressed, functional imaging technology is providing increasing insights into schizophrenia and its treatment. Future research will be truly multidisciplinary as it will require the collaboration of psychiatrists, imaging physicians, neuropsychologists and neuroscientists.

Epilepsy is a group of neurological conditions in which there is a pathological and enduring predisposition to generate recurrent seizures. Evidence over the last few decades suggests that epilepsy may be associated with increased sleep-disordered breathing, which may contribute towards sleep fragmentation, daytime somnolence, reduced seizure control, and cardiovascular-related morbidity and mortality. Chronic sleep-disordered breathing can result in loss of gray matter and cause deficits to memory and global cognitive function. Sleep-disordered breathing is a novel and independent predictor of sudden cardiac death and, as such, may be involved in the mechanisms leading to sudden unexpected death in epilepsy. Despite this, the long-term consequences of sleep-disordered breathing in epilepsy remain unknown, and there are no guidelines for screening or treating this population. There is currently insufficient evidence to indicate continuous positive airway pressure (CPAP) for the primary or secondary prevention of cardiovascular disease, and recent evidence has failed to show any reduction of fatal or nonfatal cardiovascular endpoints. Treatment of sleep-disordered breathing may potentially improve seizure control, daytime somnolence, and neurocognitive outcomes, but few studies have examined this relationship. In this review, we examine sleep-disordered breathing in epilepsy, and discuss the potential effect of epilepsy treatments. We consider the role of CPAP and other interventions for sleep-disordered breathing and discuss their implications for epilepsy management.

Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in frontostriatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter hyperintensities (WMHs) on magnetic resonance imaging has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction.