Apraxia testing to distinguish early Alzheimer's disease from psychiatric causes of cognitive impairment.

Objective: Mood- and stress-related disorders commonly cause attentional and memory impairments in middle-aged individuals. In memory testing, these impairments can be mistakenly interpreted as symptoms of dementia; thus, more reliable diagnostic approaches are needed. The present work defines the discriminant accuracy of the Dementia Apraxia Test (DATE) between psychiatric conditions and early-onset Alzheimer's disease (AD) on its own and in combination with memory tests. Method: The consecutive sample included 50-70-year-old patients referred to dementia investigations for recent cognitive and/or affective symptoms. The DATE was administered and scored as a blinded measurement, and a receiver operating curve analysis was used to define the optimal diagnostic cut-off score. Results: A total of 24 patients were diagnosed with probable AD (mean age 61 ± 4) and 23 with a psychiatric condition (mean age 57 ± 4). The AD patients showed remarkable limb apraxia, but the psychiatric patients mainly performed at a healthy level on the DATE. The test showed a total discriminant accuracy of 87% for a total sum cut-off of 47 (sensitivity 79% and specificity 96%). The limb subscale alone reached an accuracy of 91% for a cut-off of 20 (sensitivity 83% and specificity 100%). All memory tests were diagnostically less accurate, while the combination of the limb praxis subscale and a verbal episodic memory test suggested a correct diagnosis in all but one patient. Conclusions: Apraxia testing may improve the accuracy of differentiation between AD and psychiatric aetiologies. Its potential in severe and chronic psychiatric conditions should be examined in the future.

Association of biallelic RFC1 expansion with early-onset Parkinson's disease.

BACKGROUND AND PURPOSE: The biallelic repeat expansion (AAGGG)exp in the replication factor C subunit 1 gene (RFC1) is a frequent cause of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) as well as late-onset ataxia. The clinical spectrum of RFC1 disease has expanded since the first identification of biallelic (AAGGG)exp and includes now various nonclassical phenotypes. Biallelic (AAGGG)exp in RFC1 in patients with clinically confirmed Parkinson's disease (PD) has recently been found. METHODS: A nationwide cohort of 273 Finnish patients with early-onset PD was examined for the biallelic intronic expansion in RFC1. The expansion (AAGGG)exp was first screened using extra long polymerase chain reactions (Extra Large-PCRs) and flanking multiplex PCR. The presence of biallelic (AAGGG)exp was then confirmed by repeat-primed PCR and, finally, the repeat length was determined by long-read sequencing. RESULTS: Three patients were found with the biallelic (AAGGG)exp in RFC1 giving a frequency of 1.10% (0.23%-3.18%; 95% confidence interval). The three patients fulfilled the diagnostic criteria of PD, none of them had ataxia or neuropathy, and only one patient had a mild vestibular dysfunction. The age at onset of PD symptoms was 40-48 years and their disease course had been unremarkable apart from the early onset. CONCLUSIONS: Our results suggest that (AAGGG)exp in RFC1 is a rare cause of early-onset PD. Other populations should be examined in order to determine whether our findings are specific to the Finnish population.

The dementia apraxia test can detect early-onset Alzheimer's disease.

OBJECTIVE: Limb apraxia is a common early sign of Alzheimer's disease (AD) and is thought to occur specifically in early-onset (before the age of 65) AD. The Dementia Apraxia Test (DATE), a test of limb and face praxis developed to support the differential diagnosis of dementia, has shown good diagnostic accuracy in detecting AD in older patients, but it has not been validated for younger age groups. We investigated how accurately DATE can detect AD in middle-aged individuals and whether apraxia is a distinctive feature in early-onset AD. METHOD: A sample of mild-stage AD patients (n = 24; Mage = 61, SD = 4) was drawn from a prospective consecutive series of individuals referred to our neurology clinic for dementia investigations. A healthy comparison group (HC) of comparable age (n = 22; Mage = 61, SD = 7), sex distribution, and education was recruited. DATE was administered as a blinded experimental measure, and a receiver operating characteristic (ROC) analysis was used to define the optimal diagnostic cutoff point. RESULTS: The DATE classified 93% of the participants correctly as AD or HC (sensitivity 0.88, specificity 1.00, area under curve 0.968). The optimal diagnostic cutoff point was higher (49 points) than in a previous sample of older patients (45 points). Early onset did not seem to be associated with worse praxis performance in AD. CONCLUSIONS: DATE is an accurate tool for detecting early-onset AD within 2 years of symptom onset. The diagnostic cutoff point should be higher for middle-aged populations than for late-onset AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients.

BACKGROUND: Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. OBJECTIVES: To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. METHODS: In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. RESULTS: Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. CONCLUSIONS: SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.

Mutation Analysis of the Genes Linked to Early Onset Alzheimer's Disease and Frontotemporal Lobar Degeneration.

A lot of effort has been done to unravel the genetics underlying early-onset Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). However, many familial early-onset dementia (EOD) cases still show an unclear genetic background. The aim of this study was to evaluate the role of the known causative mutations and possible pathogenic variants associated with AD and FTLD in a Finnish EOD cohort. The cohort consisted of 39 patients (mean age at onset 54.8 years, range 39-65) with a positive family history of dementia or an atypical or rapidly progressive course of the disease. None of the patients carried the C9orf72 hexanucleotide repeat expansion. Mutations and variants in APP, PSEN1, PSEN2, MAPT, GRN, VCP, CHMP2B, FUS, TARDBP, TREM2, TMEM106B, UBQLN2, SOD1, PRNP, UBQLN1, and BIN1 were screened by using a targeted next generation sequencing panel. Two previously reported pathogenic mutations (PSEN1 p.His163Arg and MAPT p.Arg406Trp) were identified in the cohort. Both patients had familial dementia with an atypical early onset phenotype. In addition, a heterozygous p.Arg71Trp mutation in PSEN2 with an uncertain pathogenic nature was identified in a patient with neuropathologically confirmed AD. In conclusion, targeted investigation of the known dementia-linked genes is worthwhile in patients with onset age under 55 and a positive family history, as well as in patients with atypical features.