Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

Contribution of sleep disturbances to fatigue in multiple sclerosis: a prospective study using clinical and polysomnographic parameters.

BACKGROUND AND PURPOSE: Fatigue is amongst the most frequent and disabling symptoms of multiple sclerosis and a close relation between fatigue and sleep quality has been hypothesized. In this study the contribution of sleep disturbances measured by clinical and polysomnographic parameters to fatigue in multiple sclerosis was investigated. METHODS: This was a prospective instrumental study performed at the Neurocenter of Southern Switzerland. Demographic data and clinical characteristics including fatigue (as measured by the modified fatigue impact scale [MFIS]), neurological disability, psychiatric symptoms, medications and sleep-related variables were collected at baseline visit and by a home full-night polysomnography. The associations between sleep-related variables and the MFIS were tested using partial correlations adjusted by demographic and sleep-unrelated clinical factors. RESULTS: Seventy-six patients were included in the study, of whom 53 (69.7%) had an MFIS ≥38 points (median 49.5, interquartile range 31.0-62.0). MFIS scores were positively associated with age, neurological disability, symptoms of depression and anxiety, and use of benzodiazepines and selective serotonin reuptake inhibitors. When adjusting for these variables, the presence of restless legs syndrome (RLS) (r = 0.37, p = 0.005) and periodic leg movements index (r = -0.33, p = 0.014) were associated with MFIS. Excessive daytime sleepiness, total sleep time, sleep efficiency, respiratory disturbances, and percentage of time spent in the different sleep stages (N1, N2, N3 and rapid eye movement) were not associated with fatigue. CONCLUSIONS: Multiple sclerosis patients with a diagnosis of RLS had significantly higher global fatigue scores compared to those without RLS. Future studies should investigate whether medical treatment of RLS can ameliorate fatigue.

[The Swiss Brain Health Registry : a national infrastructure for Alzheimer's research]. / Le Registre suisse pour la santé du cerveau - Une infrastructure nationale pour la recherche sur la maladie d'Alzheimer.

The Memory Centres of several Swiss hospitals have set up a national online registry for Alzheimer's research, called www.BHR-suisse.org. This type of registry already exists in the United States (www.brainhealthregistry.org/) and the Netherlands (https://hersenonderzoek.nl/). It contributes, as do these initiating sites, to the creation of a global database of research partnersb who wish to contribute by participating in studies on neurodegenerative diseases and more particularly on Alzheimer's disease. By registering, they provide a certain amount of information and become potential research partners. Researchers can then select a panel of volunteers according to the selection and exclusion criteria of their studies, contact them and include them in their studies.

Les centres de la mémoire de plusieurs hôpitaux suisses ont créé un Registre national suisse en ligne pour la recherche sur Alzheimer, intitulé www.bhr-suisse.org. Ce type de registre existe déjà aux États-Unis (www.brainhealthregistry.org/) et aux Pays-Bas (hersenonderzoek.nl/). Il contribue, au même titre que ces sites initiateurs, à constituer une base de données globale de partenaires de recherchea qui souhaitent apporter leur contribution en participant à des études sur les maladies neurodégénératives et, plus particulièrement, sur la maladie d'Alzheimer. En s'inscrivant, ces derniers apportent un certain nombre d'informations et deviennent de potentiels partenaires de recherche. Les chercheurs peuvent ensuite sélectionner un panel suivant les critères de sélection et d'exclusion de leurs études, contacter les volontaires et les intégrer dans ces études.

Incidence of dementia in the oldest-old and its relationship with age: The Monzino 80-plus population-based study.

INTRODUCTION: Relationship between age and dementia at extreme old ages is still an open question, yet population-based studies in this high-risk age segment are rare. METHODS: The Monzino 80-plus is a population-based study among residents 80 years and older in the Varese province, Italy. Of 1371 eligible individuals, 1294 (94.4%), of whom 64 are centenarians, were included in the incidence study. RESULTS: Since 2002, 584 new cases of all-cause dementia were identified over 15 years. The overall incidence rate was 7.9 per 100 person-years. Dementia risk rose with age (IRR: 1.06), with the cubic model providing the best fit (R2  = 0.91-0.96). Cumulative incidences of dementia unadjusted and adjusted for competing mortality risk progressively diverged with age. CONCLUSION: Dementia incidence also keeps rising in nonagenarians and centenarians. Slowing down in growing risk of developing dementia with age is mainly attributable to increasing competing risk of death and resulting selective survival of individuals at lower risk of dementia.

(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography and (123) I-metaiodobenzylguanidine myocardial scintigraphy in differentiating dementia with lewy bodies from other dementias: A comparative study.

OBJECTIVE: To compare the diagnostic value of striatal (123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123) I-FP-CIT) single photon emission computed tomography (SPECT) and (123) I-metaiodobenzylguanidine ((123) I-MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types. METHODS: This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data. RESULTS: Overall, sensitivity and specificity to DLB were respectively 93% and 100% for (123) I-MIBG myocardial scintigraphy, and 90% and 76% for (123) I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased (123) I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal (123) I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with (123) I-MIBG uptake. INTERPRETATION: (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only "core feature" exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on (123) I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368-378.

Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations.

BACKGROUND: In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS: To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS: We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS: This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.

Prevalence of dementia in the oldest old: the Monzino 80-plus population based study.

BACKGROUND: Epidemiological studies commonly include too few of the oldest old to provide accurate prevalence rates of dementia in older age groups. Estimates of the number of those affected, necessary for healthcare planning, are thus flawed. The objective is to estimate the prevalence of dementia and levels of dementia severity in a very large population of oldest old and to investigate the relation between age and dementia prevalence in the extreme ages. METHODS: The Monzino 80-plus is a population-based study among residents 80 years or older in Varese province, Italy. Dementia cases were identified using a one-phase design. The survey was conducted in the participant's place of residence, whether home or institution. Both participants and informants were interviewed. Information was available for 2504 of the 2813 residents (89%). RESULTS: In all, 894 individuals (714 women and 180 men) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria for dementia, for a standardized prevalence of 25.3% (95% confidence interval [CI]: 23.4, 27.2%), 28.5% (95% CI: 26.2, 30.9) in women and 18.6% (95% CI: 15.2, 21.9) in men. Age-specific prevalence estimates of dementia increased with age from 15.7% at age 80 to 84 years to 65.9% at age 100 years and higher. For women, prevalence continued to rise after age 100 years, from 64.8% at age 100 to 101 years to 76.1% at age 102 to 107 years. After age 85 years prevalence rates tended to rise linearly, on average 2.6% per year in women and 1.8% in men. About 80% of the cases were moderate or severe. The frequency of mild dementia decreased and that of severe dementia increased with age. CONCLUSION: One-quarter of 80-plus year olds are affected by dementia, mostly moderate or severe. Prevalence rates of dementia do not level off, but continue to rise gradually even in the extreme ages.

Persistent 18F-FDG Brain PET Fronto-Temporal Hypometabolism and Cognitive Symptoms Two Years after SARS-CoV-2 Infection: A Case Report.

At least 10% of patients experience persistent symptoms after SARS-CoV-2 infection, a condition referred to as post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long COVID, long-haul COVID, long-term effects of COVID, post-COVID-19 and chronic COVID. In this report, we describe a case of persistent cognitive deficits developed after SARS-CoV-2 infection in a 40-year-old woman with a family history of early-onset Alzheimer's disease (EOAD) since her father was diagnosed with EOAD at the age of 50. We describe the clinical picture and workup, with special emphasis on the alterations of brain glucose metabolism evidenced by 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET), which could be considered a useful marker of the presence and persistence of cognitive deficits.

Transcranial Magnetic Stimulation Improves Executive Functioning through Modulation of Social Cognitive Networks in Patients with Mild Cognitive Impairment: Preliminary Results.

(1) Background: Patients with mild cognitive impairment (MCI) often present impairment in executive functions (EFs). This study aimed to investigate the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on EFs in patients with MCI. (2) Methods: A prospective trial was conducted on 11 patients with MCI. Participants underwent 25 min of 20 Hz rTMS for ten days on the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC). Before (T0) and after rTMS treatment (T1), global cognitive profile and EFs were investigated using the Montreal cognitive assessment (MoCA), trial making test (TMT) A and B, and frontal assessment battery (FAB). Depression symptoms were assessed using the geriatric depression scale (GDS). Statistical analysis included Wilcoxon signed-rank test. (3) Results: After treatment, patients showed a significant improvement in the MoCA EFs subtask (T0 vs. T1, p = 0.015) and TMT-B (T0 vs. T1, p = 0.028). Five MCI patients with EF impairment showed full recovery of these deficits. No significant changes in the GDS were observed. (4) Conclusions: rTMS stimulation over the TPJ and MPFC induced significant short-term improvements in EFs in MCI patients. These findings suggest that the TPJ and MPFC may be involved in the attention-executive skills to redirect attention toward behaviorally relevant stimuli.

Cerebrospinal Fluid HIV-1 Escape in Patients With Neurocognitive Symptoms: Pooled Data From a Neuro-HIV Platform and the NAMACO Study.

BACKGROUND: Despite modern antiretroviral therapy, human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) escape into the cerebrospinal fluid (CSF) may occur. We examined the prevalence of and factors associated with CSF HIV-1 escape among people living with HIV (PLWH) in Switzerland. SETTING: The Neurocognitive Assessment in the Metabolic and Aging Cohort study is an ongoing, prospective, longitudinal, multicenter study within the Swiss HIV Cohort Study. The neuro-HIV platform is a multidisciplinary, single-day outpatient consultation at Lausanne University Hospital. METHODS: We pooled data from the Neurocognitive Assessment in the Metabolic and Aging Cohort study and the neuro-HIV platform participants who underwent lumbar puncture between 2011 and 2019. Both patient groups had neurocognitive symptoms. Cerebrospinal fluid HIV-1 escape was defined as the presence of quantifiable CSF HIV-1 RNA when plasma HIV-1 RNA was suppressed or CSF HIV-1 RNA greater than plasma HIV-1 RNA when the latter was detectable. RESULTS: Of 1166 PLWH assessed, 288 underwent lumbar puncture. Cerebrospinal fluid HIV-1 escape was observed in 25 PLWH (8.7%) of whom 19 (76%) had suppressed plasma HIV-1 RNA. Characteristics of PLWH were comparable whether they had CSF HIV-1 escape or not, including comorbidities, time since HIV diagnosis (15 vs 16 years, P = 0.9), median CD4 nadir (158.5/mm 3 vs 171/mm 3 , P = 0.6), antiretroviral CSF penetration-effectiveness score (7 vs 7 points, P = 0.8), and neurocognitive diagnosis based on Frascati criteria and radiological findings. CONCLUSIONS: In this large pooled sample of PLWH with neurocognitive symptoms, CSF HIV-1 escape occurred in 8.7% of PLWH. People living with HIV with CSF HIV-1 escape presented no distinctive clinical or paraclinical characteristics. We conclude that lumbar puncture is unavoidable in confirming CSF HIV-1 escape.

Attentive-executive functioning and compensatory strategies in adult ADHD: A retrospective case series study.

Background: Adults with ADHD exhibit a neuropsychological profile that may present deficits in many cognitive domains, particularly attention and executive functions (EFs). However, some authors do not consider executive disfunction as an important part of the clinical profile of the syndrome; this could be related to the use of inappropriate neuropsychological tests, probably not adapted and not sufficiently ecological. Moreover, new data are required on specific correlation of attentive-executive symptoms with socio-demographic factors. Therefore, the aim of this study is to analyze the neuropsychological performance of a group of adults with ADHD, also evaluating the influence of gender, age and education level. Methods: We retrospectively collected health-related personal data of 40 adult ADHD patients, clinically diagnosed and evaluated via a battery of 4 neuropsychological tests and 1 self-administered questionnaire. Gender, age and years of education differences were assessed. Results: Attention and EFs deficits have been highlighted mainly on the d2-R and 5-point neuropsychological tests, which therefore seem to be more sensitive in measuring the attention-executive dysfunction in an adult ADHD population, than TAP Go/No-go and ROCFT. ADHD patients also manifested subjective behavioral impulsivity disorders on BIS-11. There were no statistically significant gender differences in cognitive performance. On the contrary, younger patients performed worse on subscales TAP Go/No-go errors and 5-points number of drawings, while participants with a higher education level performed better on subscales d2-R speed of execution and d2-R errors. This supports a reduction in the number of errors and the execution time as a function of older age and a higher level of education. Finally, patients with higher education also self-reported greater impulsivity in planning. Conclusion: Our preliminary findings suggest that adult ADHD is not a lifelong stable disorder, but it may change over time. Moreover, attention-executive deficits may be influenced and partially counterbalanced by experience (i.e., advancing age) and a higher level of education. This could underlie the development of specific psycho-behavioral and cognitive compensatory strategies. The use of self-administered questionnaires is therefore recommended to highlight attentional and executive difficulties that may not result in neuropsychological tests.

Social Cognition in Adult ADHD: A Systematic Review.

The aim of this systematic review was to collect and align the research on social cognition impairments in adults with Attention-deficit/hyperactivity disorder (ADHD). In particular, we selected and analyzed papers on emotion recognition and processing, Theory of Mind (TOM), empathy, and other facets of social cognition as decision making. We identified 16 papers published between 2012 and 2022 which meet inclusion criteria. Papers search, selection, and extraction followed the PRISMA guidelines. In order to summarize data from papers, we used a narrative synthesis approach. Results show different evidence of impairment in social cognition domains in adults with ADHD. Our systematic review suggests the importance of promoting more research on this topic because it is essential to keep in mind that social cognition plays a central role in socialization and social relationships.

Theory of mind in patients with mild cognitive impairment: A systematic review.

The focus of this systematic review was to collect and align studies which analyze the functionality of theory of mind (TOM) in patients with mild cognitive impairments (MCI). Specifically, we identified 20 papers published between 2012 and 2022 which met inclusion criteria. Papers search, selection, and extraction followed the PRISMA guidelines. In order to summarize data from the papers, we used a narrative synthesis approach. Results in 18 of these 20 papers show that theory of mind (TOM) is impaired in all types of MCI patients-regardless of different etiology and diagnostic criteria. Only 2 out of 20 reported no significant differences in TOM performance between MCI patients and healthy control subjects. The review additionally aimed to bundle the variety of the type of tasks used by the author to assess multiple domains of TOM. This heterogeneity does not allow us to make a comprehensive comparison between the results, so we suggest the need to align the results using the same type of tests and TOM assessment. In the end, our work highlights the 2 neuropsychological studies which confirm more of our results; due to the objective approach adopted to investigate this topic, we suggest exploring this point of view more in future research.

Emotion recognition and processing in patients with mild cognitive impairment: A systematic review.

The purpose of this study was to investigate emotion recognition and processing in patients with mild cognitive impairment (MCI) in order to update the state of current literature on this important but undervalued topic. We identified 15 papers published between 2012 and 2022 that meet the inclusion criteria. Paper search, selection, and extraction followed the PRISMA guidelines. We used a narrative synthesis approach in order to report a summary of the main findings taken from all papers. The results collected are still ambiguous: some studies did not find any differences between MCI and healthy controls (HC) groups in emotion recognition and processing, and other results reported emotion-specific deficits in emotion recognition regarding MCI patients (both regarding negative and neutral emotions). It is essential to underline that these findings could not be generalized to the whole MCI population due to the heterogeneous use of measures and composition of the sample. This does not allow us to make a comprehensive comparison between the results. Our suggestion for future research is to align the results using the same type of tests and emotion recognition assessment.

Report of a Case of Creutzfeldt-Jakob Disease With an Unusual Clinical Presentation.

We describe the clinical features, neuropsychological tests, laboratory, electroencephalography (EEG), magnetic resonance imaging (MRI) and positron emission tomography (PET) findings of a 59-year-old woman who presented to our Centre for cognitive impairment since few months, with language disturbances, particularly anomia, dyscalculia, and memory loss. The clinical and neuropsychological features were non-specific and overlapping with those of other rapidly progressing neurodegenerative disorders. However, brain MRI played a pivotal role in the diagnosis, showing cortical diffusion restriction, particularly in the parietal lobes and posterior cingulum, with sparing of the perirolandic cortex, typical of Creutzfeldt-Jakob disease (CJD). Brain MRI abnormalities were visible since the first evaluation and remained stable at 2 and 6 weeks follow up. Basal ganglia and thalami were never involved. PET showed left lateralized reduced glucose metabolism, with partial overlap with MRI signal abnormalities. Despite MRI were strongly indicative of CJD, clinical, laboratory and EEG findings did not fulfill the diagnostic criteria for CJD which applied at the time of clinical assessment. Indeed, neither myoclonus, visual or cerebellar signs or akinetic mutism were present. Also, the characteristic periodic sharp wave complexes were absent at baseline EEG, and the CSF assay for 14-3-3 was negative. We, therefore, performed a real-time quaking-induced conversion (RT-QuIC) assay on a frozen sample of corticospinal fluid (CSF), which showed a positive result. RT-QuIC is a prion protein conversion assay that has shown high diagnostic sensitivity and specificity for the diagnosis of CJD. RT-QuIC has been recently incorporated in the National CJD Research and Surveillance Unit and Center for Disease Control and Prevention (CDC) diagnostic criteria for CJD. The fatal evolution of the disease brought the patient to death 13 months after symptoms onset. Pathology proved the diagnosis of sporadic CJD, subtype MM/MV 2C.

The role of semantic knowledge on the cognitive estimation task--evidence from Alzheimer's disease and healthy adult aging.

The current study investigated the role of semantic knowledge on the Cognitive Estimation Task (CET). In an initial experiment, the CET performance of 21 patients with frontal lobe lesions was compared with 21 healthy controls. The CET was found to be sensitive to the effects of frontal lobe lesions. In Experiment 2, 175 participants aged between 18 and 87 years performed the CET to examine the effects of healthy adult aging on the task. No significant age effects were evident. In Experiment 3, 27 patients with Alzheimer's disease (AD) were compared with 27 healthy controls on the CET. AD patients produced significantly more extreme cognitive estimates than the controls. A significant correlation was found between CET performance and performance on the General Knowledge of the World Task, a task intended to assess semantic knowledge. The hypothesis is put forward that healthy older adults are able to use their intact semantic knowledge to compensate for problem-solving deficits when generating cognitive estimates. In contrast, owing to degradation in semantic abilities, AD patients are unable to benefit from semantic knowledge and instead tend to produce bizarre cognitive estimates.