Eating Disorders (EDs) show a multifactorial etiopathogenesis including environmental, psychological and biological factors. In the present study, we propose a model of interactions between genetic ...vulnerability-represented by Fat Mass and Obesity-Associated (FTO) gene-and stable psychopathological traits, such as bodily disorders and emotion dysregulation for EDs patients. The distribution of a polymorphism of the FTO (rs9939609 T>A) was evaluated in a series of 250 EDs patients and in a group of 119 healthy control subjects. Clinical data were collected through a face-to-face interview and several self-reported questionnaires were applied, including the Emotional Eating Scale and the IDentity and EAting disorders (IDEA) questionnaire for bodily disorders and self-identity. The A-allele was associated with an increased vulnerability to EDs (AA+AT genotypes frequency 72.8% in EDs vs. 52.9% in controls). The presence of the A-allele was associated with binge eating behavior, higher emotional eating and higher IDEA scores. Finally, the FTO rs9939609 SNP was found to influence the relationship between these variables, as an association between disorder of corporeality and emotional eating was found only in A-allele carriers. A-allele seems to represent a potential additive risk factor for EDs persons, with bodily disorders to develop emotional eating and binge eating behaviors.
We aimed to assess diagnostic accuracy of plasma p-tau181 and NfL separately and in combination in discriminating Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) patients ...carrying Alzheimer's Disease (AD) pathology from non-carriers; to propose a flowchart for the interpretation of the results of plasma p-tau181 and NfL. We included 43 SCD, 41 MCI and 21 AD-demented (AD-d) patients, who underwent plasma p-tau181 and NfL analysis. Twenty-eight SCD, 41 MCI and 21 AD-d patients underwent CSF biomarkers analysis (Aβ1-42, Aβ1-42/1-40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) it they were A+/T+ , or non-carriers (AP-) when they were A-, A+/T-/N-, or A+/T-/N+ according to the A/T(N) system. Plasma p-tau181 and NfL separately showed a good accuracy (AUC = 0.88), while the combined model (NfL + p-tau181) showed an excellent accuracy (AUC = 0.92) in discriminating AP+ from AP- patients. Plasma p-tau181 and NfL results were moderately concordant (Coehn's k = 0.50, p < 0.001). Based on a logistic regression model, we estimated the risk of AD pathology considering the two biomarkers: 10.91% if both p-tau181 and NfL were negative; 41.10 and 76.49% if only one biomarker was positive (respectively p-tau18 and NfL); 94.88% if both p-tau181 and NfL were positive. Considering the moderate concordance and the risk of presenting an underlying AD pathology according to the positivity of plasma p-tau181 and NfL, we proposed a flow chart to guide the combined use of plasma p-tau181 and NfL and the interpretation of biomarker results to detect AD pathology.
Background
Subjective Cognitive Decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests, showing to increase risk of Alzheimer’s ...Disease (AD). Cognitive reserve seems to influence the progression from SCD to Mild Cognitive Impairment (MCI) and to AD. The aim of our study was to investigate gender differences in cognitive reserve evaluating how sex might modulate the role of cognitive reserve on SCD.
Methods
We included 381 SCD patients who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), cognitive complaints by the Memory Assessment Clinics Questionnaire (MAC-Q), and apolipoprotein E (APOE) genotyping.
Results
The proportion between women and men was significantly different (68.7% 95% CI 63.9–73.4 vs 31.4%, 95% CI 26.6–36.0). Women were younger than men at onset of SCD and at the baseline visit (
p
= 0.021), had lower years of education (
p
= 0.007), lower TIB scores (
p
< 0.001), and higher MAC-Q scores (
p
= 0.012). TIB was directly associated with age at onset of SCD in both women and men, while years of education was inversely associated with age at onset only in women. Multivariate analysis showed that sex influences TIB independently from years of education. TIB was directly associated with MAC-Q in men.
Conclusions
Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve in women.
Plasma biomarkers are preferable to invasive and expensive diagnostic tools, such as neuroimaging and lumbar puncture that are gold standard in the clinical management of Alzheimer's Disease (AD). ...Here, we investigated plasma Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NfL) and Phosphorylated-tau-181 (pTau 181) in AD and in its early stages: Subjective cognitive decline (SCD) and Mild cognitive impairment (MCI).
This study included 152 patients (42 SCD, 74 MCI and 36 AD). All patients underwent comprehensive clinical and neurological assessment. Blood samples were collected for Apolipoprotein E (APOE) genotyping and plasma biomarker (GFAP, NfL, and pTau 181) measurements. Forty-three patients (7 SCD, 27 MCI, and 9 AD) underwent a follow-up (FU) visit after 2 years, and a second plasma sample was collected. Plasma biomarker levels were detected using the Simoa SR-X technology (Quanterix Corp.). Statistical analysis was performed using SPSS software version 28 (IBM SPSS Statistics). Statistical significance was set at p < 0.05.
GFAP, NfL and pTau 181 levels in plasma were lower in SCD and MCI than in AD patients. In particular, plasma GFAP levels were statistically significant different between SCD and AD (
=0.003), and between MCI and AD (
=0.032). Plasma NfL was different in SCD vs MCI (
=0.026), SCD vs AD (
<0.001), SCD vs AD FU (
<0.001), SCD FU vs AD (
), SCD FU vs AD FU (
), MCI vs AD (
=0.002), MCI FU vs AD (
=0.003), MCI FU vs AD FU (
=0.003) and MCI vs AD FU (
=0.003). Plasma pTau 181 concentration was significantly different between SCD and AD (
=0.001), MCI and AD (
=0.026), MCI FU and AD (
=0.020). In APOE ϵ4 carriers, a statistically significant increase in plasma NfL (
) and pTau 181 levels was found (
Moreover, an association emerged between age at disease onset and plasma GFAP (p = 0.021) and pTau181 (p < 0.001) levels.
Plasma GFAP, NfL and pTau 181 are promising biomarkers in the diagnosis of the prodromic stages and prognosis of dementia.
We analyzed the frequency of intermediate alleles (IAs) in the ATXN1, ATXN2, and HTT genes in several neurodegenerative diseases. The study included 1126 patients with Alzheimer's disease (AD), 440 ...patients with frontotemporal dementia (FTD), and 610 patients with Parkinson's disease. In all cohorts, we genotyped ATXN1 and ATXN2 CAG repeats. In addition, in the FTD cohort, we determined the number of HTT CAG repeats. The frequency of HTT IAs was higher in patients with FTD (6.9%) versus controls (2.9%) and in the C9orf72 expansion noncarriers (7.2%) versus controls (2.9%), although the difference was nonsignificant after correction for multiple testing. Compared with controls, progressive nonfluent aphasia (PNFA) groups showed a significantly higher frequency of HTT IAs (13.6% vs. 2.9% controls). For the ATXN2 gene, we observed an increase in IA frequency in AD cases (AD 4.1% vs. controls 1.8%) and in the behavioral FTD group (4.8% vs. 1.8%). For the ATXN1 gene, we found a significant increase of IAs in patients with PNFA (18.6%) versus controls (6.7%). In conclusion, our work suggests that the HTT and ATXN1 IAS may contribute to PNFA pathogenesis and point to a link between ATXN2 IAS and AD.
•HTT and ATXN1 intermediate alleles (IAs) are associated with progressive nonfluent aphasia.•ATXN2 IAs are increased in Alzheimer's disease and behavioral frontotemporal dementia.•Our results suggest a potential link between IAs with tauopathies.
Background and objectives: Huntington’s disease (HD) is characterized by motor, cognitive and psychiatric manifestations and caused by an expansion of CAG repeats over 35 triplets on the huntingtin ...(HTT) gene. However, expansions in the range 27–35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and evaluate any differences between bipolar patients carrying the normal HTT allele and patients with the expanded HTT gene. Methods: We assessed the HTT genotype in an Italian cohort of 69 patients who were affected by either type 1 or type 2 bipolar disorder. Results: No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at the onset of psychiatric symptoms than non-carriers. Conclusion: The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls. The identification of this subset of bipolar subjects has implications for the clinical management of patients and their family members and promotes further investigation into possible pathological mechanisms common to both HD and bipolar disorder.
Background A hexanucleotide repeat expansion in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis or frontotemporal ...lobar degeneration (FTLD). Atypical presentations have been described, particularly psychosis. Methods We determined the frequency of the hexanucleotide repeat expansions in a population of 651 FTLD patients and compared the clinical characteristics of carriers and noncarriers. In addition, we genotyped 21 patients with corticobasal syndrome, 31 patients with progressive supranuclear palsy, and 222 control subjects. Results The pathogenic repeat expansion was detected in 39 (6%) patients with FTLD (17 male and 22 female subjects); however, it was not detected in any corticobasal syndrome and progressive supranuclear palsy patients or controls. Twenty-four of 39 carriers had positive family history for dementia and/or amyotrophic lateral sclerosis (61.5%), whereas only 145 of 612 noncarriers had positive family history (23.7%; p <.000001). Clinical phenotypes of carriers included 29 patients with the behavioral variant frontotemporal dementia (bvFTD; 5.2% of all bvFTD cases), 8 with bvFTD/motor neuron disease (32% bvFTD/motor neuron disease cases), 2 with semantic dementia (5.9% of patients with semantic dementia), and none with progressive nonfluent aphasia. The presentation with late-onset psychosis (median age = 63 years) was more frequent in carriers than noncarriers (10/33 vs. 3/37, p = .029), as well as the presence of cognitive impairment at onset (15/33 vs. 5/37; p = .0039). Conclusions The repeat expansion in C9ORF72 is a common cause of FTLD and often presents with late-onset psychosis or memory impairment.
•EEG reveals differences between prodromal stages of Alzheimer’s Disease.•Microstates analysis yield more inter-condition differences than spectral and network metrics.•Microstate C topography ...differs significantly in patients positive to cerebrospinal fluid Alzheimer’s biomarkers.
Alzheimer’s disease (AD) pathological changes may begin up to decades earlier than the appearance of the first symptoms of cognitive decline. Subjective cognitive decline (SCD) could be the first pre-clinical sign of possible AD, which might be followed by mild cognitive impairment (MCI), the initial stage of clinical cognitive decline. However, the neural correlates of these prodromic stages are not completely clear yet. Recent studies suggest that EEG analysis tools characterizing the cortical activity as a whole, such as microstates and cortical regions connectivity, might support a characterization of SCD and MCI conditions. Here we test this approach by performing a broad set of analyses to identify the prominent EEG markers differentiating SCD (n = 57), MCI (n = 46) and healthy control subjects (HC, n = 19). We found that the salient differences were in the temporal structure of the microstates patterns, with MCI being associated with less complex sequences due to the altered transition probability, frequency and duration of canonic microstate C. Spectral content of EEG, network connectivity, and spatial arrangement of microstates were instead largely similar in the three groups. Interestingly, comparing properties of EEG microstates in different cerebrospinal fluid (CSF) biomarkers profiles, we found that canonic microstate C displayed significant differences in topography in AD-like profile. These results show that the progression of dementia might be associated with a degradation of the cortical organization captured by microstates analysis, and that this leads to altered transitions between cortical states. Overall, our approach paves the way for the use of non-invasive EEG recordings in the identification of possible biomarkers of progression to AD from its prodromal states.
As disease-modifying therapies (DMTs) for Alzheimer's disease (AD) are becoming a reality, there is an urgent need to select cost-effective tools that can accurately identify patients in the earliest ...stages of the disease. Subjective Cognitive Decline (SCD) is a condition in which individuals complain of cognitive decline with normal performances on neuropsychological evaluation. Many studies demonstrated a higher prevalence of Alzheimer's pathology in patients diagnosed with SCD as compared to the general population. Consequently, SCD was suggested as an early symptomatic phase of AD. We will describe the study protocol of a prospective cohort study (PREVIEW) that aim to identify features derived from easily accessible, cost-effective and non-invasive assessment to accurately detect SCD patients who will progress to AD dementia.
We will include patients who self-referred to our memory clinic and are diagnosed with SCD. Participants will undergo: clinical, neurologic and neuropsychological examination, estimation of cognitive reserve and depression, evaluation of personality traits, APOE and BDNF genotyping, electroencephalography and event-related potential recording, lumbar puncture for measurement of Aβ
, t-tau, and p-tau concentration and Aβ
/Aβ
ratio. Recruited patients will have follow-up neuropsychological examinations every two years. Collected data will be used to train a machine learning algorithm to define the risk of being carriers of AD and progress to dementia in patients with SCD.
This is the first study to investigate the application of machine learning to predict AD in patients with SCD. Since all the features we will consider can be derived from non-invasive and easily accessible assessments, our expected results may provide evidence for defining cost-effective and globally scalable tools to estimate the risk of AD and address the needs of patients with memory complaints. In the era of DMTs, this will have crucial implications for the early identification of patients suitable for treatment in the initial stages of AD.
NCT05569083.
Due to continuous advances in intensive care technology and neurosurgical procedures, the number of survivors from severe acquired brain injuries (sABIs) has increased considerably, raising several ...delicate ethical issues. The heterogeneity and complex nature of the neurological damage of sABIs make the detection of predictive factors of a better outcome very challenging. Identifying the profile of those patients with better prospects of recovery will facilitate clinical and family choices and allow to personalize rehabilitation. This paper describes a multicenter prospective study protocol, to investigate outcomes and baseline predictors or biomarkers of functional recovery, on a large Italian cohort of sABI survivors undergoing postacute rehabilitation.
All patients with a diagnosis of sABI admitted to four intensive rehabilitation units (IRUs) within 4 months from the acute event, aged above 18, and providing informed consent, will be enrolled. No additional exclusion criteria will be considered. Measures will be taken at admission (T0), at three (T1) and 6 months (T2) from T0, and follow-up at 12 and 24 months from onset, including clinical and functional data, neurophysiological results, and analysis of neurogenetic biomarkers.
Advanced machine learning algorithms will be cross validated to achieve data-driven prediction models. To assess the clinical applicability of the solutions obtained, the prediction of recovery milestones will be compared to the evaluation of a multiprofessional, interdisciplinary rehabilitation team, performed within 2 weeks from admission.
Identifying the profiles of patients with a favorable prognosis would allow customization of rehabilitation strategies, to provide accurate information to the caregivers and, possibly, to optimize rehabilitation outcomes.
The application and validation of machine learning algorithms on a comprehensive pool of clinical, genetic, and neurophysiological data can pave the way toward the implementation of tools in support of the clinical prognosis for the rehabilitation pathways of patients after sABI.
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