Evaluating Semantic Knowledge Through a Semantic Association Task in Individuals With Dementia.

Conceptual knowledge is supported by multiple semantic systems that are specialized for the analysis of different properties associated with object concepts. Various types of semantic association between concrete concepts-categorical (CA), encyclopedic (EA), functional (FA), and visual-encyclopedic (VEA) associations-were tested through a new picture-to-picture matching task (semantic association task, SAT). Forty individuals with Alzheimer's disease (AD), 13 with behavioral variant of frontotemporal dementia (bv-FTD), 6 with primary progressive aphasia (PPA), and 37 healthy participants were tested with the SAT.

Anxiety and Depression Are Not Related to Increasing Levels of Burden and Stress in Caregivers of Patients With Alzheimer's Disease.

Sixty-nine dyads of patients with Alzheimer's disease and primary caregivers have been followed up for 1 year to evaluate cognitive (Mini-Mental State Examination), functional (Instrumental Activities of Daily Living), and behavioral (Neuropsychiatric Inventory) decline of patient in relation to burden (Caregiver Burden Inventory), stress (Relative Stress Scale), anxiety (State-Trait Anxiety Inventory Y), and depression (Beck Depression Inventory) reported by the caregivers. After 1 year of observation, cognitive and functional scores worsened while behavioral problems remained unchanged and relatively mild in patients. After 1 year, caregivers' scores of scales of anxiety and depression decreased significantly, while stress scores remained unchanged and burden slightly increased.

Complexity in neuropsychological assessments of cognitive impairment: A network analysis approach.

In a neuropsychological assessment, each test aims at measuring a single cognitive function. However, test performance depends on an interconnected system of cognitive functions and individual characteristics. For a better understanding of cognitive deficits, it is fundamental to recognize this complexity and study the relationships between test performances.

The Mediating Role of Romantic Attachment in the Relationship Between Attachment to Parents and Aggression.

Background: A secure attachment style could promote more intimacy in romantic relationships, while an insecure attachment style could be correlated with less positive romantic relationships in adulthood. Numerous studies have noted that a secure attachment to parents was correlated with lower levels of aggression, whereas insecure attachments were associated with higher levels of aggression. We aimed to investigate the role of the attachment system as a mediator of the expression of aggressiveness during adolescence.

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.

Background: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease.

CHRNA7 Gene and Response to Cholinesterase Inhibitors in an Italian Cohort of Alzheimer's Disease Patients.

Previous studies suggest that genetic variants in CHRNA7, which encodes for the major subunit of the acetylcholine receptor (α7-nAChR), are associated with the clinical response to cholinesterase inhibitors (ChEI) in Alzheimer's disease (AD) patients. We sought to replicate the association of two SNPs in the CHRNA7 gene, rs6494223 and rs8024987, with response to ChEI treatment in an Italian cohort of 169 AD patients, further extending the study to gene-level analysis. None of the tested variants was associated with clinical response.

Prevalence of peripheral nervous system complications after major heart surgery.

We evaluated 374 consecutive patients from May 2013 to April 2014 who underwent major cardiac surgery. Each patient had an interview and a neurological clinical examination during the rehabilitation period. Patients with possible peripheral nervous system (PNS) complications underwent further electrodiagnostic tests.

A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia.

Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD.

Transmembrane protein 106B gene (TMEM106B) variability and influence on progranulin plasma levels in patients with Alzheimer's disease.

We carried out an association study of transmembrane protein 106B gene (TMEM106B) rs1020004 A/G, rs6966915C/T, and rs1990622 A/G in a population of 656 patients with Alzheimer's disease (AD) and 619 controls, and tested whether the rs1990622 influences plasma progranulin levels. No differences in allele and genotype distribution were observed between cases and controls, even stratifying according to APOE status (p > 0.05).

Frontotemporal dementia and its subtypes: a genome-wide association study.

Background: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72--have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.

CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study.

As neuroinflammation is an early event in the pathogenesis of Alzheimer' s disease, new selective antiinflammatory drugs could lead to promising preventive strategies. We evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of CHF5074, a new microglial modulator, in a 12-week, double-blind, placebo-controlled, parallel groups, ascending dose study involving 96 MCI patients. Subjects were allocated into three successive study cohorts to receive ascending, titrated doses of CHF5074 (200, 400 or 600 mg/day) or placebo.

Disruption of structural connectivity along the dorsal and ventral language pathways in patients with nonfluent and semantic variant primary progressive aphasia: a DT MRI study and a literature review.

Nonfluent (NFV) and semantic (SV) variants of primary progressive aphasia (PPA) are associated with distinct patterns of focal cortical atrophy and underlying pathology. Previous diffusion tensor (DT) MRI studies showed a more ventral white matter (WM) involvement in SV patients and a more widespread frontal involvement in NFV. Aim of this manuscript is twofold.

Multiplex assessment of a panel of 16 serum molecules for the differential diagnosis of Alzheimer's disease.

One of the current challenge in Alzheimer's disease (AD) is the identification of reliable biomarkers that might improve diagnostic accuracy, possibly correlating with the disease progression and patient's response to therapy. As the clinically validated AD biomarkers evaluate cerebrospinal fluid (CSF) parameters, the need for less invasive diagnostic markers is well evident. To this respect, blood circulating cytokines or growth factors have provided some encouraging results, even though no clinically validated to date.

Autosomal dominant frontotemporal lobar degeneration due to the C9ORF72 hexanucleotide repeat expansion: late-onset psychotic clinical presentation.

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.

Expression of the transcription factor Sp1 and its regulatory hsa-miR-29b in peripheral blood mononuclear cells from patients with Alzheimer's disease.

Altered gene expression occurs in central nervous system disorders, including Alzheimer's disease (AD). Transcription factor Sp1 (specificity protein 1) can regulate the expression of several AD-related proteins, including amyloid-β protein precursor and tau. Sp1 is regulated by oxidative stress, and Sp1 mRNA was found to be upregulated in AD cortex and hippocampus.

Monocyte chemoattractant protein-1 promoter polymorphism and plasma levels in alzheimer's disease.

Background: Neurodegenerative disorders such Alzheimer's disease (AD) are often characterized by senile plaques and neurofibrillary tangle. In addition, reactive astrogliosis, microglia activation and a chronic inflammation are found in AD brain. Activated microglia has been reported to express a large number of beta chemokines including monocyte chemoattractant protein-1 (MCP-1).

Pharmacogenomics in Alzheimer's disease: a genome-wide association study of response to cholinesterase inhibitors.

We conducted a genome-wide association study in a cohort of 176 Italian Alzheimer's disease (AD) patients with extreme phenotype of response to cholinesterase inhibitors. Patients were classified into responders in case of positive, stable, or ≤1 worsening of mini-mental state examination score and into nonresponders if >3 points worsening during a median follow-up of 0.85 years of treatment.

Genetics and expression analysis of the specificity protein 4 gene (SP4) in patients with Alzheimer's disease and frontotemporal lobar degeneration.

Transcription factor Sp4 (Specificity protein 4) levels are increased in the brain of patients with Alzheimer's disease (AD), and Sp4 colocalizes with neurofibrillary tangles. Moreover, SP4 is a susceptibility gene for bipolar disorder and schizophrenia, which share many clinical features with frontotemporal lobar degeneration (FTLD). The distribution of three tagging single nucleotide polymorphisms(SNPs)-rs9639379, rs10272006, and rs6461569-has been determined in a population of 352 patients diagnosed clinically with AD, 290 patients with FTLD, and 341 age-matched controls.

GOOD or BAD responder? Behavioural and neuroanatomical markers of clinical response to donepezil in dementia.

We explored the neuropsychological and neuromorphometrical differences between probable Alzheimer's disease patients showing a good or a bad response to nine months treatment with donepezil. Before treatment, the neuropsychological profile of the two patient groups was perfectly matched. By the ninth month after treatment, the BAD-responders showed a decline of the MMSE score together with a progressive impairment of executive functions.

Replication study to confirm the role of CYP2D6 polymorphism rs1080985 on donepezil efficacy in Alzheimer's disease patients.

Alzheimer's disease (AD) is a neurodegenerative disorder often treated with donepezil, an acetylcholinesterase inhibitor. Response to donepezil is variable, probably based on patients' genetic background in donepezil metabolizing enzymes, including cytochrome 2D6 (CYP2D6). We evaluated the association between clinical response to donepezil and a common variant (rs1080985) of CYP2D6, previously reported to be associated with poor response to the drug.

When Rey-Osterrieth's Complex Figure Becomes a Church: Prevalence and Correlates of Graphic Confabulations in Dementia.

Verbal confabulation (VC) has been described in several pathological conditions characterized by amnesia and has been defined as 'statements that involve distortion of memories'. Here we describe another kind of confabulation (graphic confabulation, GC), evident at the recall of the Rey-Osterrieth complex figure (ROCF). In a retrospective study of 267 patients with mild-to-moderate dementia, 14 patients (4.

CSF metabolites in the differential diagnosis of Alzheimer's disease from frontal variant of frontotemporal dementia.

The early differentiation between Alzheimer's disease (AD) and frontal variant of frontotemporal dementia (fvFTD) is frequently difficult, albeit critical for the adequate management of patients and their caregivers. In order to assess the accuracy of CSF levels of beta-amyloid 1-42 (Aβ), tau (τ) and Thr 181-phosphorilated tau (Pτ) in the early differentiation of AD from fvFTD, we designed a prospective study in which patients have been followed up for at least 2 years. Seventy-two patients with AD and 42 patients with fvFTD showed significantly different CSF levels of Pτ (increased in AD, p = 0.

Cerebrospinal fluid biomarkers in Progranulin mutations carriers.

Cerebrospinal fluid (CSF) biomarkers (Aβ₁₋₄₂, total tau, P-181 tau) are currently used to support a clinical diagnosis of Alzheimer's disease (AD). The CSF profile in frontotemporal lobar degeneration (FTLD) caused by Progranulin (GRN) mutation is unknown. We assessed CSF biomarkers in 145 AD, 140 FTLD (20 GRN positive, 120 GRN negative) patients, and 38 controls.

Role of OLR1 and its regulating hsa-miR369-3p in Alzheimer's disease: genetics and expression analysis.

The oxidized LDL receptor 1 gene (OLR1) rs1050283 single nucleotide polymorphism (SNP) has been previously shown to be associated with Alzheimer's disease (AD). An association analysis of OLR1 was carried out in a population of 443 patients with AD as compared with 393 age-matched controls. In addition, an expression analysis of OLR1 and its regulatory hsa-miR369-3p was performed in peripheral mononuclear blood cells (PBMC) from 20 patients and 15 controls.

A Population-based study of dementia in the oldest old: the Monzino 80-plus study.

Background: Despite being the fastest growing and the most cognitively impaired age group, the oldest olds are under-represented in clinical research. The purpose of this study was to describe the design, methods, and baseline characteristics of the survey population and investigate possible differences in demographic, cognitive, functional, and behavioral characteristics between oldest old with and without any performance on cognitive tests and between oldest old alive and those deceased prior to the interview.

Methods: The Monzino 80-plus Study is a prospective door-to-door population-based survey among 80 years or older residents in the municipalities in the province of Varese, Italy.