Association between dietary exposure to chemical contaminants and risk of dementia in older persons.

Background: Diet is a major route of exposure to potentially neurotoxic chemicals, yet the epidemiological association of diet contaminants with dementia is unknown. We studied the link between dietary exposure to multiple chemicals and dementia risk in older persons, considering interaction with dietary fat content, which may modify the bioavailability and toxicity of (lipophilic) chemicals.

Methods: We included 1,288 non-demented participants from the French Three-City cohort who answered a food frequency questionnaire and 24-hour recall at baseline and were followed for incident dementia.

Assessment of Mendelian and risk-factor genes in Alzheimer disease: A prospective nationwide clinical utility study and recommendations for genetic screening.

Purpose: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD).

Methods: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients.

Plasma lysosphingolipids in GRN-related diseases: Monitoring lysosomal dysfunction to track disease progression.

GRN mutations are among the main genetic causes of frontotemporal dementia (FTD). Considering the progranulin involvement in lysosomal homeostasis, we aimed to evaluate if plasma lysosphingolipids (lysoSPL) are increased in GRN mutation carriers, and whether they might represent relevant fluid-based biomarkers in GRN-related diseases. We analyzed four lysoSPL levels in plasmas of 131 GRN carriers and 142 non-carriers, including healthy controls and patients with frontotemporal dementias (FTD) carrying a C9orf72 expansion or without any mutation.

Effect of the Histone Deacetylase Inhibitor FRM-0334 on Progranulin Levels in Patients With Progranulin Gene Haploinsufficiency: A Randomized Clinical Trial.

Importance: Histone deacetylase inhibitors have been repeatedly shown to elevate progranulin levels in preclinical models. This report describes the first randomized clinical trial of a histone deacetylase inhibitor in frontotemporal dementia (FTD) resulting from progranulin (GRN) gene variations.

Objective: To characterize the safety, tolerability, plasma pharmacokinetics, and pharmacodynamic effects of oral FRM-0334 on plasma progranulin and other exploratory biomarkers, including fluorodeoxyglucose (FDG)-positron emission tomography (PET), in individuals with GRN haploinsufficiency.

Plasma NfL levels and longitudinal change rates in and -associated diseases: from tailored references to clinical applications.

Objective: Neurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in and cohorts from presymptomatic to clinical stages.

Methods: We analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of and patients, presymptomatic carriers (PS) and controls aged between 21 and 83.

Primary Progressive Aphasia Associated With Mutations: New Insights Into the Nonamyloid Logopenic Variant.

Objective: To determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with (progranulin) mutations and to study their neuroanatomic correlates.

Methods: Patients with PPA carrying mutations (PPA-) were selected among a national prospective research cohort of 1,696 patients with frontotemporal dementia, including 235 patients with PPA. All patients with amyloid-positive CSF biomarkers were excluded.

Improving the Diagnosis of the Frontal Variant of Alzheimer's Disease with the DAPHNE Scale.

Background: The frontal variant of Alzheimer's disease (fAD) is poorly understood and poorly defined. The diagnosis remains challenging. The main differential diagnosis is the behavioral variant of frontotemporal degeneration (bvFTD).

Does amnesia specifically predict Alzheimer's pathology? A neuropathological study.

Amnesia is a key component of Alzheimer's disease (AD) and the most important feature of its clinical diagnosis but its specificity has recently been challenged. This study investigated the ability of amnesia to predict AD in a clinicopathological dementia series. Ninety-one patients to which free and cued verbal memory assessment was administered during early cognitive decline, were followed until autopsy.

Plasma progranulin levels for frontotemporal dementia in clinical practice: a 10-year French experience.

GRN mutations are frequent causes of familial frontotemporal degeneration. Although there is no clear consensual threshold, plasma progranulin levels represent an efficient biomarker for predicting GRN mutations when decreased. We evaluated plasma levels to determine whether it could also predict age at onset, clinical phenotype, or disease progression in 160 GRN carriers.

Diabetes-Associated Dementia Risk and Competing Risk of Death in the Three-City Study.

Diabetes is associated with a higher dementia and mortality risk. However, few studies have accounted for death when estimating the association between diabetes and dementia. We estimated absolute and relative risks of all-cause dementia according to diabetes exposure status in older adults while accounting for competing risk of death using illness-death models.

Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer's Disease Before 51 Years.

Background: Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer's disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants.

Objective: To describe the proportion of each genetic variation among patients with very young-onset sporadic AD.

Are visual cues helpful for virtual spatial navigation and spatial memory in patients with mild cognitive impairment or Alzheimer's disease?

Objective: To evaluate whether visual cues are helpful for virtual spatial navigation and memory in Alzheimer's disease (AD) and patients with mild cognitive impairment (MCI).

Method: 20 patients with AD, 18 patients with MCI and 20 age-matched healthy controls (HC) were included. Participants had to actively reproduce a path that included 5 intersections with one landmark at each intersection that they had seen previously during a learning phase.

APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases.

Background: Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series.

Methods And Findings: We report here a novel update (2012-2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170.

Symptomatic treatments in Alzheimer's disease in 2016: a study from Memory centers in France.

Cholinesterase inhibitors and memantine are used from 15 years, in Alzheimer's disease. Benefits have been demonstrated according to cognition, activities of daily living, affective symptoms and behavior, and global impression of change. The aims of this paper are: 1) to describe how these treatments are used in France with a sample survey managed by the national federation of the french CMRR; 2) to study data about efficacy, safety, medicoeconomic impacts and how they are used in Europe.

Gender effect on driving cessation in pre-dementia and dementia phases: results of the 3C population-based study.

Objectives: Aging entails deterioration in sensory, physical, and cognitive functions, raising doubt in the driving capacity of older drivers, especially when the deficits are severe, as in dementia. Many older drivers, especially women, adapt their driving habits in order to compensate for these deficits and eventually stop driving. The present prospective study assessed driving cessation in men and women throughout the dementia process, including a 2-year pre-dementia phase.

Defining the spectrum of frontotemporal dementias associated with TARDBP mutations.

Objectives: We describe the largest series of patients with TARDBP mutations presenting with frontotemporal dementia (FTD) and review the cases in the literature to precisely characterize FTD diseases associated with this genotype.

Methods: The phenotypic characteristics of 29 TARDBP patients, including 10 new French and Dutch cases and 19 reviewed from the literature, were evaluated.

Results: The most frequent phenotype was a behavioral variant frontotemporal dementia (bvFTD), but a significant proportion (40%) of our patients had semantic (svFTD) or nonfluent variants (nfvFTD) at onset; and svFTD was significantly more frequent in TARDBP carriers than in other FTD genotypes (p < 0.

Semantic and nonfluent aphasic variants, secondarily associated with amyotrophic lateral sclerosis, are predominant frontotemporal lobar degeneration phenotypes in TBK1 carriers.

Introduction: TBK1 mutations represent a rare novel genetic cause of amyotrophic lateral sclerosis (ALS) without or with dementia. The full spectrum of TBK1 phenotypes has not been completely defined so far.

Methods: We describe the clinical and neuroimaging characteristics of loss-of-function mutation carriers initially presenting with frontotemporal lobar degeneration (FTLD) phenotypes.

DAPHNE: A New Tool for the Assessment of the Behavioral Variant of Frontotemporal Dementia.

Background: The diagnosis of behavioral variant of frontotemporal dementia (bvFTD) relies primarily on clinical features and remains challenging. The specificity of the recently revised criteria can be disappointing, justifying development of new clinical tools.

Objective: We produced a behavioral inventory named DAPHNE.

Usefulness of data from magnetic resonance imaging to improve prediction of dementia: population based cohort study.

Objective: To determine whether the addition of data derived from magnetic resonance imaging (MRI) of the brain to a model incorporating conventional risk variables improves prediction of dementia over 10 years of follow-up.

Design: Population based cohort study of individuals aged ≥ 65.

Setting: The Dijon magnetic resonance imaging study cohort from the Three-City Study, France.

Dementia pugilistica: a severe tribute to a career.

A 59-year-old man, ex-professional boxer, met clinical criteria for probable Alzheimer's disease. The patient agreed to be included in a clinico-pathological study with donation to the brain bank, and he died at 71. The brain was grossly atrophic, with a prominent atrophy of the entorhinal cortex and hippocampus, and with pallor of the substantia nigra.

Everyday-like memory for objects in ageing and Alzheimer's disease assessed in a visually complex environment: The role of executive functioning and episodic memory.

To investigate everyday memory, more and more studies rely on virtual-reality applications to bridge the gap between in situ approaches and laboratory settings. In this vein, the present study was designed to assess everyday-like memory from the virtual reality-based Human Object Memory for Everyday Scenes (HOMES) test (Sauzéon et al., , Exp.

Time course of brain volume changes in the preclinical phase of Alzheimer's disease.

Background: Structural alterations of a large network characterize Alzheimer's disease (AD), but the time course of these changes remains unclear. The dynamic of these alterations was examined in the AD preclinical phase using data from the 10-year follow-up of a population-based cohort (Bordeaux-3City).

Methods: Participants received neuropsychological assessments every 2 years and two identical magnetic resonance imaging (MRI) exams at baseline and 4 years later.

Natural history of functional decline in Alzheimer's disease: a systematic review.

Background: Knowledge of functional evolution in dementia is crucial for the patients and their families as well as the clinician.

Objective: This review identifies scales and outcomes used to describe the natural history of functional decline and describes the natural history of functional decline in a representative clinical population sample of published studies of patients with Alzheimer's disease (AD).

Methods: A search of three relevant databases was conducted and limited to articles published in English and French between 1998 to March 2012, using the keywords "Dementia", "Activities of Daily Living", "Instrumental Activities of Daily Living", "Functional Impairment", "Prognosis", and "Disease Progression".

Estrogen receptor polymorphisms and incident dementia: the prospective 3C study.

Background: Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors.

Methods: The association between five ESR α (ESR1) and β (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipoprotein E (APOE) ε4 allele, and hormone treatment were considered as potential effect modifiers of this association.