A digital teleneuropsychology platform for the diagnosis of mild cognitive impairment: from concept to certification as a medical device.

BACKGROUND: Innovative digital solutions are shaping a new concept of dementia care, opening additional venues for prevention, diagnosis, monitoring and treatment. Hereby, we report the development of a tablet-based teleneuropsychology platform (Tenèpsia®), from concept to certification as Medical Device (MD) Class IIA, as per new MD regulation 745/2017. METHODS: The platform was designed for the remote cognitive evaluation and created thanks to the effort of a collaborative working group including experts from three Italian scientific societies and Biogen Italia S.r.l. (hereafter "Biogen"), and developers from Xenia Reply and Inside AI. The development strategy was guided by converting traditional paper-and-pencil tests into digital versions while maintaining comparable neuropsychological features and optimizing patient accessibility and user experience. The experts focused on the choice and adaptation of traditional neuropsychology measures for a 45-min teleneuropsychology assessment. RESULTS: The developers created a web and a mobile interface, respectively, for the professional (neuropsychologist) and non-professional (patient and caregiver) use. Recording of voice, drawing and typing information was enabled. Instant dashboards provide a quick overview of the patient's condition. Simulation activities were performed to obtain MD certification, valid across Europe. CONCLUSION: Neuropsychology services will benefit from the implementation in clinics of harmonized digital tools with adequate scientific and technological standards. The use of digital cognitive testing for the diagnosis of mild cognitive impairment is expected to enhance patient and clinician outcomes through simplified, digital objective data collection, sparing of time and resources, with a positive impact on healthcare costs and access to treatments, reducing inequalities and delays in diagnosis and cure.

Memory biases in Alzheimer's disease and mild cognitive impairment. A systematic review and metanalysis.

Several studies demonstrated that individuals are more likely to remember emotional than neutral information; this phenomenon is known as emotional enhancement of memory (EEM). Adults generally tend to remember negative information more efficiently than neutral or positive items. In contrast, healthy elders seem to show an opposite bias for positive information, but results are inconsistent, also because during aging, elaboration of emotional information could change as a consequence of cognitive impairment. In this systematic review and meta-analysis, we conducted literature search of studies investigating emotion memory biases in mild cognitive impairment (MCI) and Alzheimer's disease (AD) on PubMed, Scopus and PsycINFO databases following PRISMA guidelines. The findings showed that emotional memory biases are still present despite the presence of cognitive impairment, both in MCI and at least in early stages of AD. However, the direction of emotion memory biases is not consistent across studies. These results suggest that patients with cognitive impairment might still benefit from EEM and help to define targets of intervention for cognitive rehabilitation in pathological aging.

Time of isolation, education and gender influence the psychological outcome during COVID-19 lockdown in caregivers of patients with dementia.

PURPOSE: The study evaluated the effects of the COVID-19 emergency lockdown on the psychological outcome in caregivers (children or spouses) of patients with dementia and the loss of the welfare services in these patients. METHODS: Zung's depression and anxiety assessment scales and the Perceived Stress Scale were administered by a telephone interview or a self-compilation directly on the online platform. RESULTS: The sample consisted of 239 participants (men = 124; women = 115) with a mean age of 54.4 years (SD = 12.1). Education was associated with significantly lower overall anxiety and depression scores while days of isolation and female gender were associated with the higher scores. A marked reduction of health services was observed in all patients. CONCLUSION: The lockdown registered a particular impact on people with dementia and their caregivers. Many people with dementia were deprived of care services and time of isolation had a significant negative effect on anxiety and depression in caregivers.

Non-invasive brain stimulation in generalized anxiety disorder: A systematic review.

In the last years, several studies using non-invasive brain stimulation (NIBS) techniques demonstrated that the dorsolateral prefrontal cortex (DLPFC) plays a key role in the neurobiological bases of anxiety disorders. Both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) applied primarily over the prefrontal cortex have been shown to modulate anxiety symptomatology and attention allocation in the generalized anxiety disorder. A literature search on PubMed and PsycINFO databases following PRISMA guidelines identified 4 TMS studies (one open-label study and three randomized trials with active/sham conditions) and one tDCS case report study that have applied NIBS in patients with GAD. All the studies targeted the DLPFC except one in which the parietal cortex has been stimulated. Overall, the findings would suggest that NIBS could ameliorate anxiety symptoms and that improvements remained stable in the follow-up. Although a limited number of NIBS studies has been conducted on patients with anxiety disorders, these techniques could represent promising tools for the study of neurofunctional basis of anxiety disorders. Further sham-controlled studies are needed to clarify the mechanisms of action of NIBS in order to optimize stimulation protocols and to verify their effectiveness for treating anxiety symptoms.

Familial dominant epilepsy and mild pachygyria associated with a constitutional LIS1 mutation.

We describe a mother and son with focal epilepsy, mild cognitive impairment, and pachygyria, which was parieto-occipital in the mother and with remarkable posterior greater than anterior severity in the son. Overall clinical manifestations, although overlapping in type, were likewise slightly more severe in the son. Using targeted resequencing through a gene panel for malformations of cortical development, we identified the c.655 T > A [p.(Trp219Arg)] novel missense variant in the LIS1 gene, segregating in the proband and in his mother. Western Blot analysis, qPCR gene expression and RT-PCR disclosed no significant differences between proband, his parents, and controls. Epilepsy and mild cognitive impairment can be the only clinical presentation of constitutional LIS1 mutations, which can therefore be inherited if the associated phenotype implies limited or no reproductive disadvantage. Parents of patients harboring LIS1 mutations should be assessed for their mutation carrier status.

Clinical features and outcome of 6 new patients carrying de novo KCNB1 gene mutations.

OBJECTIVE: To describe electroclinical features and outcome of 6 patients harboring KCNB1 mutations. METHODS: Clinical, EEG, neuropsychological, and brain MRI data analysis. Targeted next-generation sequencing of a 95 epilepsy gene panel. RESULTS: The mean age at seizure onset was 11 months. The mean follow-up of 11.3 years documented that 4 patients following an infantile phase of frequent seizures became seizure free; the mean age at seizure offset was 4.25 years. Epilepsy phenotypes comprised West syndrome in 2 patients, infantile-onset unspecified generalized epilepsy, myoclonic and photosensitive eyelid myoclonia epilepsy resembling Jeavons syndrome, Lennox-Gastaut syndrome, and focal epilepsy with prolonged occipital or clonic seizures in each and every one. Five patients had developmental delay prior to seizure onset evolving into severe intellectual disability with absent speech and autistic traits in one and stereotypic hand movements with impulse control disorder in another. The patient with Jeavons syndrome evolved into moderate intellectual disability. Mutations were de novo, 4 missense and 2 nonsense, 5 were novel, and 1 resulted from somatic mosaicism. CONCLUSIONS: KCNB1-related manifestations include a spectrum of infantile-onset generalized or focal seizures whose combination leads to early infantile epileptic encephalopathy including West, Lennox-Gastaut, and Jeavons syndromes. Long-term follow-up highlights that following a stormy phase, seizures subside or cease and treatment may be eased or withdrawn. Cognitive and motor functions are almost always delayed prior to seizure onset and evolve into severe, persistent impairment. Thus, KCNB1 mutations are associated with diffuse brain dysfunction combining seizures, motor, and cognitive impairment.

Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.

Targeted resequencing gene panels are used in the diagnostic setting to identify gene defects in epilepsy. We performed targeted resequencing using a 30-genes panel and a 95-genes panel in 349 patients with drug-resistant epilepsies beginning in the first years of life. We identified 71 pathogenic variants, 42 of which novel, in 30 genes, corresponding to 20.3% of the probands. In 66% of mutation positive patients, epilepsy onset occurred before the age of 6 months. The 95-genes panel allowed a genetic diagnosis in 22 (6.3%) patients that would have otherwise been missed using the 30-gene panel. About 50% of mutations were identified in genes coding for sodium and potassium channel components. SCN2A was the most frequently mutated gene followed by SCN1A, KCNQ2, STXBP1, SCN8A, CDKL5, and MECP2. Twenty-nine mutations were identified in 23 additional genes, most of them recently associated with epilepsy. Our data show that panels targeting about 100 genes represent the best cost-effective diagnostic option in pediatric drug-resistant epilepsies. They enable molecular diagnosis of atypical phenotypes, allowing to broaden phenotype-genotype correlations. Molecular diagnosis might influence patients' management and translate into better and specific treatment recommendations in some conditions.