The Italian Validation of the Beck Cognitive Insight Scale: Underlying Factor Structure in Psychotic Patients and the General Population.

Cognitive insight refers to the ability to question one's judgments and cognitive biases and is underpinned by specific metacognitive processes. The Beck Cognitive Insight Scale was developed to assess cognitive insight and includes two subscales, Self-Reflectiveness and Self-Certainty (SC). The present study aimed to investigate the underlying factor structure of the Italian version of the BCIS in patients with schizophrenia (SZ) and in the general population (GP) for the first time. A cross-sectional design was adopted and a GP sample of 624 subjects and an SZ sample of 130 patients were enrolled. In the SZ group, a two-factor solution was supported. The internal reliability of each factor was satisfactory. Two items were eliminated and one item moved from the SC to the SR subscale. In the GP group, a two-factor solution was highlighted. The internal reliability of each factor was satisfactory. However, four items of the SR subscale were deleted. The Italian-validated version of the BCIS shows different structures for the SZ and the GP and is characterized by different features concerning previous studies. This evidence suggests new interpretations of metacognitive processes in the two populations and implies specific therapeutic approaches.

A new scale to assess technostress levels in an Italian banking context: the Work-Related Technostress Questionnaire.

Introduction: Technostress (TS) represents a multidimensional phenomenon closely related to the pervasive use of information and communication technologies. This study aimed to validate a new psychometric tool for assessing TS in an Italian banking context, the Work-Related Technostress - Questionnaire (WRT-Q). Secondly, we analyzed the role of gender and age in modulating TS manifestations. Methods: A sample of 2,586 bank employees (51% females; age: 47.26 ± 8.6) underwent an online survey. Reliability, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), ANCOVA, independent sample t-test, and correlation analyses were performed. Results: The WRT-Q consisted of 17 items and a four-factor structure, supported by the following CFA indices: Comparative Fit Index (CFI) = 0.985; Incremental Fit Index (IFI) = 0.985; Goodness of Fit (GFI) = 0.988; Root Mean Squared Error of Approximation (RMSEA) = 0.071; and SRMR = 0.062. A significant difference in TS levels between age classes emerged (p < 0.001) with higher levels in the over 55-year-old subgroup, while no statistically significant difference emerged for gender. Moreover, the whole sample found a significant positive association between age and TS (p < 0.001). Discussion: The WRT-Q is a new instrument to measure TS in the workplace, it can contribute to highlighting adverse outcomes in individuals due to a dysfunctional interaction with ICT.

A New Look on Long-COVID Effects: The Functional Brain Fog Syndrome.

Epidemiological data and etiopathogenesis of brain fog are very heterogeneous in the literature, preventing adequate diagnosis and treatment. Our study aimed to explore the relationship between brain fog, neuropsychiatric and cognitive symptoms in the general population. A sample of 441 subjects underwent a web-based survey, including the PANAS, the DASS-21, the IES-R, the Beck Cognitive Insight Scale, and a questionnaire investigating demographic information, brain fog, subjective cognitive impairments (Scc) and sleep disorders. ANOVA, ANCOVA, correlation and multiple stepwise regression analyses were performed. In our sample, 33% of participants were defined as Healthy Subjects (HS; no brain fog, no Scc), 27% as Probable Brain Fog (PBF; brain fog or Scc), and 40% as Functional Brain Fog (FBF; brain fog plus Scc). PBF and FBF showed higher levels of neuropsychiatric symptoms than HS, and FBF showed the worst psychological outcome. Moreover, worse cognitive symptoms were related to the female gender, greater neuropsychiatric symptoms, sleep disorders, and rumination/indecision. Being a woman and more severe neuropsychiatric symptoms were predictors of FBF severity. Our data pointed out a high prevalence and various levels of severity and impairments of brain fog, suggesting a classificatory proposal and a multifaceted etiopathogenic model, thus facilitating adequate diagnostic and therapeutic approaches.

COVID-19 and Stressful Adjustment to Work: A Long-Term Prospective Study About Homeworking for Bank Employees in Italy.

The COVID-19 evolution has forced the massive introduction of homeworking (HW) for most employees in the initial stages of the pandemic and then return to work, mainly due to the vaccination campaign. These multiple abrupt adjustment demands in work may be a source of intense stress for office workers with consequences on wellbeing and the quality of life. This long-term prospective study aimed at investigating the effect of adaptation demands on a broad population of employees of a large Italian banking group in the job-related stress framework. We administered a web-based survey to 1,264 participants in Reopening after the first lockdown, from June to October 2020, at 841 subjects in Second Wave, corresponding to the rise of contagions from November 2020 to January 2021, and to 491 individuals in Vaccination Round, which ranged from February to June 2021. We assessed workaholism by using the Dutch Work Addiction Scale (DUWAS-10), work-family conflicting overlap by using the Work and Family Conflict Scale (WAFCS), and concern for back to work (BW) and for HW by specific questions. Higher WAFCS scores characterized Reopening and Vaccination Round while Second Wave had the highest level of concern for HW. Women and younger individuals showed the highest concern for BW, WAFCS, and DUWAS-10 scores regardless of the pandemic stage. HW days per week were related to more heightened concern for BW and lower concern for HW, DUWAS, and WAFCS scores. The number of children was related to lower Concern for BW and higher WAFCS scores in Reopening and Second Wave. Our data showed that massive adjustment demands in work and family routine represented a significant source of stress for employees, regardless of the different pandemic stages. The highest level of fatigue emerged in women and younger subjects. These results shed light on the need for a road map to promote a gradual and structured adjustment for workers and encourage organizations to consider homeworking as a valid stable alternative.

Mental health in the post-lockdown pandemic phase: Relief or exacerbation of psychological distress? A cross-sectional study in the general population in Italy.

This study is one of the first aiming at investigating the mental health in the post-lockdown period in an Italian adult population and detecting demographic and psychological predictors for a worse outcome. 1401 participants answered a web-based survey including the Emotional Reaction Questionnaire (ERQ), the Positive Affect and Negative Affect Scale (PANAS), the Impact of Event Scale-Revised (IES-R), the General Health Questionnaire (GHQ), the Depression, Anxiety and Stress Scale (DASS-21), and the Dutch Work Addiction Scale (DUWAS). Simple slope analyses highlighted that women, lower age, and suppression were related to higher scores for the PANAS negative affect scale, the DASS-21, the IES-R, the GHQ, and the DUWAS. In our sample, 1.2% of participants showed depressive symptoms, 0.5% anxiety symptoms, and 2% stress symptoms. Moreover, 5.4% of participants reported post-traumatic symptoms and 15% signs of psychological distress. Compared with data on the lockdown period, our results show lower levels of depressive, anxiety, and stress symptoms, possibly due to the slackening of preventive measures adopted since June. Despite this, post-traumatic symptoms and signs of psychological distress were still present. Our data suggest the necessity to monitor psychological adaption over time in general and at-risk subjects.

The Relation Between Consumers' Frontal Alpha Asymmetry, Attitude, and Investment Decision.

The frontal alpha asymmetry (FAA) is a neurophysiological measure of motivation and preference. Despite the FAA is associated to commercial pleasantness, conflicting evidence emerged in the literature regarding its relationship with behavior. To study the association between FAA and consumers' decision, we manipulated a commercial script to elicit diverse consumers' attitudes and decisions and to evaluate whether the FAA score is associated to their final investment. A little informative script (S1) was used to polarize consumers' attitudes and investments toward unfavorable scores, while a more personalized message (S2) to elicit in customers a favorable attitude and higher investments. Twenty-one participants listened to the scripts, and their FAA, attitude, and monetary investment were measured. In S1, the FAA did not correlate with neither attitude nor the investment decision, while a robust negative correlation between these variables was found in S2. No other peripheral body and neural measures associated with attitude or final decision. Our data suggest that the FAA correlates with attitude and decision, when a commercial script is customized and provides an adequate information, likely leading the consumer to a more reasoned and planned decision-making process. When facilitating a favorable attitude toward an offer, the negative correlation of FAA and behavior may reflect the involvement of a control system, whose role is to monitor and govern possible conflicts between approach and avoidance motivations. This observation provides additional indication on the value of FAA as a marker of consumer behaviors, and how it could be affected by experimental and contextual bias.

Neuropsychiatric symptoms differently affect mild cognitive impairment and Alzheimer's disease patients: a retrospective observational study.

Alzheimer's disease (AD) is the most common form of dementia characterized by the prevalent memory impairment. Mild cognitive impairment (MCI) may represent the early stage of AD, in particular when MCI patients show biomarkers consistent with AD pathology (MCI due to AD). Neuropsychiatric symptoms (NPS) frequently affect both MCI and AD patients. Cerebrospinal-fluid (CSF) tau and ß-amyloid42 (Aß42) levels are actually considered the most sensitive and specific biomarkers for AD neurodegeneration. In the present retrospective observational study, we evaluated CSF biomarkers and neuropsychological data (also including NPS measured by the neuropsychiatric inventory-NPI) in a population of patients affected by MCI due to AD compared with mild to moderate AD patients. We documented higher NPI scores in MCI compared with AD patients. In particular, sub-items related to sleep, appetite, irritability, depression, and anxiety were higher in MCI than AD. We also found the significant correlation between NPS and CSF AD biomarkers in the whole population of MCI and AD patients. Consistently, t-tau/Aß42 ratio correlated with NPS in all the MCI and AD patients. These results suggest the more prevalent occurrence of NPS in MCI patients showing AD pathology and converting to dementia than AD patients. Moreover, a more significant degree of AD neurodegeneration, featured by high t-tau/Aß42 ratio, correlated with more severe NPS, thus supposing that in MCI and AD patients a more extensive AD neurodegeneration is related to more severe behavioral disturbances.

Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment.

Alzheimer's disease (AD) is a fatal dementing neurodegenerative disease, currently lacking an efficacious disease-modifying therapy. In the last years, there has been some interest in the use of homotaurine as a potential therapeutic compound for AD, but more work is still needed to prove its efficacy as disease modifier in dementia. Since inflammation is believed to play a key role in AD development, we sought to investigate here the in vivo homotaurine effect on inflammatory response in patients at the earliest stages of AD, i.e., suffering from amnestic mild cognitive impairment (aMCI). Thus, the present study aims to evaluate the effects of homotaurine supplementation on cytokine serum levels and memory performances in MCI patients. Neuropsychological, clinical and cytokine assessment was performed at baseline (T0) and after 1 year (T12) of homotaurine supplementation in 20 patients categorized as carriers (n = 9) or no carriers (n = 11) of the ε4 allele of the apolipoprotein E (APOE) gene, the strongest genetic risk factor for AD. The serum levels of the pro-inflammatory mediators Interleukin (IL) 1ß, Tumor necrosis factor-alpha (TNFα), IL-6 and IL-18, contextually with the anti-inflammatory molecules IL-18 binding protein (IL-18BP) and Transforming growth factor-beta (TGFß), were analyzed to explore significant differences in the inflammatory status between T0 and T12 in the two APOE variant carrier groups. No significant differences over time were observed in patients as for most cytokines, except for IL-18. Following homotaurine supplementation, patients carrying the APOEε4 allele showed a significant decrease in IL-18 (both in its total and IL-18BP unbound forms), in turn associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI may have a positive consequence on episodic memory loss due, at least in part, to homotaurine anti-inflammatory effects. This study strongly suggests that future research should focus on exploring the mechanisms by which homotaurine controls brain inflammation during AD progression.

IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study.

OBJECTIVE: Interaction between the nervous and immune systems may influence emotions, ultimately affecting human health. Cytokines may play a role in developing emotional dysregulation as in alexithymia, a personality construct characterized by the subclinical inability to identify and describe emotions, often associated with several psychiatric and psychosomatic disorders. The proinflammatory cytokine IL-18, with a recognized role in brain functions, may influence serotonin metabolism and appears to be associated with alexithymia. Healthy individuals carrying the long allele (L) of the serotonin transporter gene polymorphic region (5-HTTLPR), and thus having lower concentrations of serotonin in the synaptic cleft, show a greater tendency toward alexithymia, with some gender differences. To explore a potential physiological interaction between IL-18, serotonin neurotransmission, and alexithymia, we investigated whether IL-18 serum levels and 5-HTTLPR are linked to alexithymic traits in healthy subjects. METHODS: We measured IL-18 serum levels in 115 Italian-Caucasian healthy subjects genotyped for 5-HTTLPR allele variants, divided by gender and assessed for alexithymia scores using the 20-item Toronto Alexithymia Scale. RESULTS: IL-18 levels are significantly more elevated in individuals with the LL genotype (n = 25) than in carriers of the short allele (n = 90, p = 0.0073). Specifically, in LL males (n = 11), i.e., the group with the most relevant increase in IL-18, cytokine values positively correlated with difficulty identifying feelings, which is a component of alexithymia (r = 0.634, p = 0.036). CONCLUSIONS: These results indicate a possible novel interaction between IL-18 and the serotoninergic system to mediate emotional unawareness, suggesting putative biological predictors of emotional dysregulation, which in turn can act as a risk factor for a variety of medical conditions in susceptible subjects.

Anosognosia for cognitive and behavioral symptoms in Parkinson's disease with mild dementia and mild cognitive impairment: Frequency and neuropsychological/neuropsychiatric correlates.

INTRODUCTION: Anosognosia is a multidimensional phenomenon with detrimental effects on patients' illness course, therapy compliance and quality of life. We aimed at investigating anosognosia for cognitive and behavioral symptoms in Parkinson's Disease (PD) with dementia (PDD) and, for the first time, in PD with Mild Cognitive Impairment (MCI-PD). METHODS: Community dwelling subjects (47 mild PDD, 136 multidomain MCI-PD (mdMCI-PD), 5 single domain MCI-PD (sdMCI-PD), and 197 PD without cognitive impairment (noCI-PD) were enrolled in a cross-sectional design study. All the subjects were administered the Anosognosia Questionnaire for Dementia, the Mental Deterioration Battery and a number of neuropsychiatric inventories. RESULTS: A diagnosis of anosognosia was made in 36% of patients with mild PDD and 16% with mdMCI-PD, whether it was negligible in sdMCI-PD and noCI-PD. Higher severity of anosognosia for cognitive impairment was also found in PDD and in mdMCI-PD. SdMCI-PD had the lower severity of anosognosia for cognitive impairment. Higher anosognosia for cognitive impairment was associated to lower depression in noCI-PD (r = -0.227, p = 0.0013) and mdMCI-PD (r = -0.266, p = 0.0016), and to reduced hedonic tone in noCI-PD (r = -0.191, p = 0.0071). Greater anosognosia was associated to lower executive performances in PDD (r = 0.424, p = 0.0074). CONCLUSIONS: Anosognosia for non-motor symptoms is frequent in PD patients with mild dementia or mdMCI. Results confirm the role of neuropsychiatric characteristics in anosognosia also in PD, the high prevalence of anosognosia in neurodegenerative illnesses and suggest a common pathogenic path for anosognosia in different neurodegenerative and psychiatric disorders.

LC-MS/MS simultaneous analysis of allopregnanolone, epiallopregnanolone, pregnanolone, dehydroepiandrosterone and dehydroepiandrosterone 3-sulfate in human plasma.

AIM: Several neuropsychopharmacological properties have been attributed to the 3α-reduced pregnane steroids, allopregnanolone and pregnanolone, as well as to dehydroepiandrosterone sulfate because of their ability to modulate γ-aminobutyric acid (GABAA) receptors in the CNS. In order to understand better their role in several mechanisms in CNS, a new methodology is proposed to monitor these compounds in human plasma. Methodology & results: The analytes were first derivatized with 2-hydrazinopyridine and extracted from plasma using SPE. Then, the compounds were separated and detected by LC-MS/MS. A mobile phase of formic acid (0.1%) in water and methanol through a gradient of composition and a flow rate of 0.3 ml min-1 resulted in good separations of the analytes. Linear responses in wide range of concentrations and LOQs ranging from 10 (dehydroepiandrosterone 3-sulfate) to 40 pg ml-1 (dehydroepiandrosterone) were obtained in <9 min. The method proposed has been validated and then applied to monitor these neurosteroids in plasma samples from ten volunteers. CONCLUSION: For the first time, a straightforward and reliable method for the chromatographic separation of allopregnanolone, epiallopregnanolone and pregnanolone, as well as of dehydroepiandrosterone and dehydroepiandrosterone 3-sulfate was carried out, with optimal accuracy, sensitivity and specificity.

Unrealistic self-overconfidence in schizophrenia is associated with left presubiculum atrophy and impaired episodic memory.

The study aimed at investigating the role of the hippocampal subfields in cognitive insight and the clinical and neuropsychological underpinnings of the related two sub-dimensions, Self-Reflectiveness (SR), i.e., openness to external feedback, and Self-Certainty (SC), i.e., unrealistic overconfidence in one's opinions. In order to do this, 45 patients with a diagnosis of schizophrenia and 45 age- and gender-matched healthy control subjects (HC) were administered the Beck Cognitive Insight Scale (BCIS), along with neuropsychological, clinical and psychopathological assessment, and underwent an MRI investigation. Hippocampal segmentation was carried out. Regression analyses were performed for BCIS indexes, volumetric parameters of hippocampal subfields and clinical and neuropsychological variables. Results highlighted that in the schizophrenia group, higher levels of SC were related to reduced volume of the left presubiculum, and worse episodic memory. No significant relationship emerged for the SR index. There was no significant relationship between any of the BCIS indexes and volumetric data of the hippocampal subfields in the HC group. Our data support the hypothesis that unrealistic self-overconfidence in schizophrenia is related to the hippocampal presubiculum atrophy, which is involved in episodic memory and cognitive control and is supposed to be underpinned by difficulty in integrating new memories and thus in generating new hypotheses about the self.

Alexithymia in Parkinson's disease: A systematic review of the literature.

INTRODUCTION: In this systematic review, we aimed to evaluate the role of alexithymia in Parkinson's disease (PD) and its relationship to neurological, neuropsychiatric, cognitive, and neuroimaging correlates. METHODS: The database was selected using PubMed Services, Cochrane, PsycNET and Scopus and a number of key words. Further studies were sought by manually searching for secondary sources, including relevant journals and references in primary articles. The search was restricted to articles written in English between January 1980 and August 2015. RESULTS: Ten studies reported that alexithymia prevalence was about double in PD patients compared to control subjects and that specific dimensions of alexithymia might be related to depression, anxiety, apathy and impulsivity. Some studies investigated the relationship between alexithymia and neuropsychological symptoms and found correlations with frontal and parietal lobe functions. Two studies on neurological features reported a link between alexithymia and disease stage or a specific motor subtype of PD; the remaining studies found that alexithymia was independent from neurological symptoms, dopaminergic therapy and laterality of motor symptom onset. Data on neuroimaging correlates and therapeutic intervention on alexithymia in PD patients are still lacking. CONCLUSION: Although results suggest that alexithymia is a primary characteristics of PD, further studies with larger patient samples are needed to definitively clarify the impact of alexithymia on the clinical features of PD patients.

Myeloid dendritic cells are decreased in peripheral blood of Alzheimer's disease patients in association with disease progression and severity of depressive symptoms.

BACKGROUND: Dendritic cells (DCs) are major orchestrators of immune responses and inflammation. They are migratory cells, which may play a role in Alzheimer's disease (AD), as suggested by prior in vitro studies. With the intent to investigate the clinical relevance of DC modifications in vivo, the present study was aimed to evaluate the levels of blood DCs in AD patients, in relation to the progression of the disease, the severity of its symptoms, and the treatment with acetylcholinesterase inhibitors (AChEIs), a class of drugs used to improve cognitive functioning in people with dementia. METHODS: The two main subpopulations of immature blood DCs, namely myeloid (mDCs) and plasmacytoid (pDCs) cells, were evaluated by flow cytometry analysis in 106 AD patients, in comparison with the same cells from 65 individuals with mild cognitive impairment (MCI) and 73 healthy control subjects (HC). The relationship between blood DC levels and symptom severity was also assessed in AD patients, and their blood DC frequency was considered both in the absence or presence of treatment with AChEIs. RESULTS: A significant depletion in blood mDCs was observed in AD patients, as compared to HC and MCI subjects. At variance, pDC levels were comparable among the three groups of subjects. The mDC decrease was evident only after the emergence of AD clinical symptoms, as confirmed by the follow-up analysis of a subgroup of MCI subjects who exhibited a significant decline in mDCs after their conversion to AD. Notably, the mDC decline was inversely correlated in AD patients with the frequency and severity of depressive symptoms. Eventually, the mDC depletion was not observable in patients treated with AChEIs. CONCLUSIONS: Our results provide the first evidence that blood mDC levels are dysregulated in AD. This phenomenon appears mainly linked to AD progression, associated with stronger severity of AD-related symptoms, and influenced by AChEI treatment. Taken all together, these data suggest that blood mDCs may serve as a cell source to test disease-induced and treatment-related changes and support the innovative notion that DCs play a role in AD, as ultimate evidence of the immune system participation in disease progression.

Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

The superficial white matter in Alzheimer's disease.

White matter abnormalities have been shown in the large deep fibers of Alzheimer's disease patients. However, the late myelinating superficial white matter comprised of intracortical myelin and short-range association fibers has not received much attention. To investigate this area, we extracted a surface corresponding to the superficial white matter beneath the cortex and then applied a cortical pattern-matching approach which allowed us to register and subsequently sample diffusivity along thousands of points at the interface between the gray matter and white matter in 44 patients with Alzheimer's disease (Age: 71.02 ± 5.84, 16M/28F) and 47 healthy controls (Age 69.23 ± 4.45, 19M/28F). In patients we found an overall increase in the axial and radial diffusivity across most of the superficial white matter (P < 0.001) with increases in diffusivity of more than 20% in the bilateral parahippocampal regions and the temporal and frontal lobes. Furthermore, diffusivity correlated with the cognitive deficits measured by the Mini-Mental State Examination scores (P < 0.001). The superficial white matter has a unique microstructure and is critical for the integration of multimodal information during brain maturation and aging. Here we show that there are major abnormalities in patients and the deterioration of these fibers relates to clinical symptoms in Alzheimer's disease.

Self-awareness in Mild Cognitive Impairment: Quantitative evidence from systematic review and meta-analysis.

Here we quantitatively summarized evidence of impaired awareness in Mild Cognitive Impairment (MCI) and meta-analytically explored the relationship between Subjective Cognitive Complaints (SCC) and actual cognitive impairment. Twenty-three studies were included, 14 comparing awareness measures in MCI and healthy elderly subjects, and 16 also exploring the neuropsychological underpinnings of impaired awareness. Moderator analyses were conducted to determine whether self-awareness varied according to patient group, the particular state in relation to which insight was assessed, or the approach to measuring awareness. The meta-analysis shows that MCI patients have knowledge of their neuropsychological deficits and that level of awareness varies according to cognitive status, language and memory abilities. The assessment technique employed impacted on the insight phenomena. Specifically, MCI patients seem particularly accurate in evaluating the current state of their performance during an ongoing task and this could be essential in regulating their behavior so that compensative strategies are practiced and greater cognitive independence is achieved. Thus, assessment technique and cognitive status are crucial factors that influence level of awareness and should be taken into consideration in awareness evaluation and rehabilitation.

Inverse effect of the APOE epsilon4 allele in late- and early-onset Alzheimer's disease.

In Alzheimer's disease patients (AD), the age at onset (AAO) ranges from 40 to 90. Usually, AD patients who develop symptoms before the age of 65 are classified as early onset (EO). The best known genetic risk factor for AD is the ε4 allele of the apolipoprotein E (APOE). In this study, 474 subjects with AD were consecutively recruited in the memory clinic of the Santa Lucia Foundation in Rome. The best fitting model  for the discrimination between EO and late onset (LO) was chosen based on lowest value of the Bayesian Information Criterion, which suggests the theoretical model with minimal deviation from the empirical distribution function of AAO in our sample. The FMM was used to compare EO and LO groups with respect to the following demographic and clinical variables: gender, age, education, MMSE and NPI. Furthermore a quantitative assessment of ADL and IADL was performed. Finally, the frequency of the APOE ε4 allele was compared in EO and LO groups. Using the admixture analysis, we established that the AAO discriminating EO from LO-AD was 63-64. Higher education was associated with earlier onset in the EO but not in LO, and duration of illness was associated with earlier onset only in LO. The ε4 allele was associated with later onset in EO but earlier onset in LO. Finally, increased impairment in ADL, IADL and NPI was associated with later onset only in the LO subgroup. Thus, the ε4 allele of the APOE gene was significantly associated with both EO and LO distributions but with opposite effect, suggesting genetic heterogeneity. Additional studies are needed to further clarify the genetic mechanisms differentiating EO- and LO-AD.

Corpus Callosum Structure is Topographically Correlated with the Early Course of Cognition and Depression in Alzheimer's Disease.

Corpus callosum (CC) abnormalities may cause cognitive and neuropsychiatric complications due to reduced hemispheric integration. Over a one-year period, we investigated whether the CC structure of 20 patients with mild Alzheimer's disease (AD) was linked to the evolution of cognitive and neuropsychiatric symptoms. We also investigated whether this anatomical-clinical relationship was localized topographically on the CC by combining voxel-based morphometry and diffusion tensor imaging approaches. We assessed patients' global cognitive deterioration and neuropsychiatric symptoms with the Mini-Mental State Examination and the Neuropsychiatric Inventory. Increased global cognitive deterioration during the early course of AD was significantly related to reduced white matter density (p = 0.004) and fractional anisotropy (FA) (p = 0.012) and increased mean diffusivity (MD) (p = 0.017) at the level of the CC isthmus/splenium. Further, increased depression severity was significantly related to reduced FA (p = 0.008) and increased MD (p = 0.018) at the level of the CC rostrum. These results indicate that changes in early myelinated CC fibers, which subserve the lateral temporal and parietal cortices and are less vulnerable to damage, may be related to cognitive impairment. Furthermore, changes in late myelinated CC fibers, which connect the orbitofrontal cortices and are more vulnerable to damage, may be related to the earliest neuropsychiatric symptoms of AD, such as depression.