Alzheimer frontal variant

OBJECTIVE: Early-onset frontal variant of Alzheimer's disease (fvAD) is characterized by apathy, disinhibition, and executive dysfunction. As such, fvAD is often difficult to clinically distinguish from behavioral variant frontotemporal dementia (bvFTD). However, research suggests that a differentiating feature among the two conditions is that fvAD typically presents with more pronounced memory impairment. Therefore, neuropsychological testing in the context of a comprehensive multidisciplinary assessment can be a valuable tool to aid with differential diagnosis...

BACKGROUND: The mild behavioral impairment checklist (MBI-C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer's Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD). METHODS: Fifty-two patients with bvFTD (mild, n = 30; moderate-severe, n = 22) and 82 community-dwelling elderly individuals (HCs) were enrolled...

OBJECTIVE: To explore the neuroimage change in Parkinson's disease (PD) patients with cognitive impairments, this study investigated the correlation between plasma biomarkers and morphological brain changes in patients with normal cognition and mild cognitive impairment. The objective was to identify the potential target deposition regions of the plasma biomarkers and to search for the relevant early neuroimaging biomarkers on the basis of different cognitive domains. METHODS: Structural brain MRI and diffusion weighted images were analyzed from 49 eligible PD participants (male/female: 27/22; mean age: 73...

Early pathological features of frontotemporal lobar degeneration (FTLD) due to MAPT pathogenic variants (FTLD-MAPT) are understudied, since early-stage tissue is rarely available. Here, we report unique pathological data from three presymptomatic/early-stage MAPT variant carriers (FTLD Clinical Dementia Rating [FTLD-CDR] = 0-1). We examined neuronal degeneration semi-quantitatively and digitally quantified tau burden in 18 grey matter (9 cortical, 9 subcortical) and 13 white matter (9 cortical, 4 subcortical) regions...

Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social, economic, and emotional burden for the patients and caregivers. It is characterised by a (at least initially) selective degeneration of the frontal and/or temporal lobe, generally leading to behavioural alterations, speech disorders, and psychiatric symptoms. Despite the recent advances, given its extreme heterogeneity, an overview that can bring together all the data currently available is still lacking...

BACKGROUND: The identification of pathogenic mutations in Alzheimer's disease (AD) causal genes led to a better understanding of the pathobiology of AD. Familial Alzheimer's disease (FAD) is known to be associated with mutations in the APP, PSEN1, and PSEN2 genes involved in Aβ production; however, these genetic defects occur in only about 10-20% of FAD cases, and more genes and new mechanism causing FAD remain largely obscure. METHODS: We performed exome sequencing on family members with a FAD pedigree and identified gene variant ZDHHC21 p...

BACKGROUND: Frontal variant Alzheimer's disease (fvAD) is considered a rare form of Alzheimer's disease (AD) which may be misdiagnosed as behavioural variant frontotemporal dementia (bvFTD). The literature has tended to conflate behavioural and executive dysfunction in fvAD cohorts and uses both AD diagnostic criteria and bvFTD diagnostic criteria to classify fvAD cohorts. The primary aim of this narrative synthesis was to summarise neuropsychological findings in fvAD cohorts in the context of established AD pathology...

In his epoch-making monograph, Wernicke (1874) claimed that atrophy of the brain cannot cause aphasia. Refuting this claim, Pick (1892, 1898, 1901, 1904a) documented in increasing detail several cases of aphasia with circumscribed atrophy of the left temporal lobe, frontal lobe, or both, which persuaded Wernicke (1906). To explain why the atrophy is circumscribed and leads to focal symptoms, Pick (1908a) advanced a functional network account. Behavioral, neuroanatomical, and histopathological studies by Dejerine and Sérieux, Fischer, Alzheimer, Altman, Gans, Onari and Spatz, and Stertz further illuminated the clinical syndromes, the exact spatial distributions of the atrophy, the underlying disease, and its laminar specificity...

Although social functioning relies on working memory, whether a social-specific mechanism exists remains unclear. This undermines the characterization of neurodegenerative conditions with both working memory and social deficits. We assessed working memory domain-specificity across behavioral, electrophysiological, and neuroimaging dimensions in 245 participants. A novel working memory task involving social and non-social stimuli with three load levels was assessed across controls and different neurodegenerative conditions with recognized impairments in: working memory and social cognition (behavioral-variant frontotemporal dementia); general cognition (Alzheimer's disease); and unspecific patterns (Parkinson's disease)...

Colony-stimulating factor 1 receptor-related adult-onset leukoencephalopathy is a primary microgliopathy characterized by a complex phenotype, which can be easily misdiagnosed with other leukoencephalopathy and neurodegenerative diseases such as frontotemporal dementia. It is estimated to be the most common adult-onset leukodystrophy. Here, we report the case of a 67-year-old man with a history of progressive impairment of behavioral and cognitive functions, including apathy, inhibition, tendency to mutism, and deficits in complex planning skills...

Behavioral variant frontotemporal dementia (bvFTD) belongs to the spectrum of frontotemporal lobar degeneration (FTLD) and is characterized by frontal dysfunction with executive deficits and prominent socio-emotional impairments. Social cognition, such as emotion processing, theory of mind, and empathy may significantly impact daily behavior in bvFTD. Abnormal protein accumulation of tau or TDP-43 are the main causes of neurodegeneration and neurocognitive decline. However, differential diagnosis is difficult due to the heterogeneous pathology in bvFTD and the high clinicopathological overlap with other FTLD syndromes, especially in late disease stages...

BACKGROUND: Primary progressive aphasia (PPA) is a group of neurodegenerative disorders including Alzheimer's disease and frontotemporal dementia characterized by language deterioration. Transcranial direct current stimulation (tDCS) is a non-invasive intervention for brain dysfunction. OBJECTIVE: To evaluate the tolerability and efficacy of tDCS combined with speech therapy in the three variants of PPA. We evaluate changes in fMRI activity in a subset of patients...

BACKGROUND: The insula is the predominant brain region impaired in behavior variant frontotemporal dementia (bvFTD). However, structural and functional changes in the sub-insula in the asymptomatic stage of bvFTD are unknown. OBJECTIVE: To describe structural and functional changes in insula subregions in asymptomatic carriers of the P301L mutation of the microtubule-associated protein tau (MAPT) gene and patients with bvFTD. METHODS: Six asymptomatic MAPT P301L mutation carriers and 12 MAPT negative control subjects of the same pedigree were enrolled, along with 30 patients with a clinical diagnosis of bvFTD and 30 matched controls...

The rare A673T variant was the first variant found within the amyloid precursor protein (APP) gene conferring protection against Alzheimer's disease (AD). Thereafter, different studies have discovered that the carriers of the APP A673T variant show reduced levels of amyloid beta (Aβ) in the plasma and better cognitive performance at high age. Here, we analyzed cerebrospinal fluid (CSF) and plasma of APP A673T carriers and control individuals using a mass spectrometry-based proteomics approach to identify differentially regulated targets in an unbiased manner...

Cannabis use disorder (CUD) is common and has in part a genetic basis. The risk factors underlying its development likely involve multiple genes that are polygenetic and interact with each other and the environment to ultimately lead to the disorder. Co-morbidity and genetic correlations have been identified between CUD and other disorders and traits in select populations primarily of European descent. If two or more traits, such as CUD and another disorder, are affected by the same genetic locus, they are said to be pleiotropic...

INTRODUCTION: To investigate the role and influence of apraxia regarding dementia severity in Alzheimer's disease (AD). In addition, to examine whether apraxia or its association to dementia severity show distinct characteristics between typical and atypical variants of AD, that commonly include frontal, logopenic, posterior, and Down's syndrome variant. METHOD: The search conducted on 4 December 2020 in the Cinahl, Ovid Medline, PsycArticles, PsycInfo, Scopus and Web of Science databases yielded 251 non-duplicate records published since 2000...

BACKGROUND: Progranulin (GRN) mutations in frontotemporal dementia (FTD) have been less frequently reported in China than in Western countries. OBJECTIVE: This study reports a novel GRN mutation and summarizes the genetic and clinical features of patients with GRN mutations in China. METHODS: Comprehensive clinical, genetic, and neuroimaging examinations were conducted on a 58-year-old female patient diagnosed with semantic variant primary progressive aphasia...

Abnormal reward processing is a hallmark of neurodegenerative diseases, most strikingly in frontotemporal dementia. However, the phenotypic repertoire and neuroanatomical substrates of abnormal reward behaviour in these diseases remain incompletely characterized and poorly understood. Here we addressed these issues in a large, intensively phenotyped patient cohort representing all major syndromes of sporadic frontotemporal dementia and Alzheimer's disease. We studied 27 patients with behavioural variant frontotemporal dementia, 58 with primary progressive aphasia (22 semantic variant, 24 non-fluent/agrammatic variant and 12 logopenic) and 34 with typical amnestic Alzheimer's disease, in relation to 42 healthy older individuals...

AIMS: To estimate the proportions of specific hypometabolic patterns and their association with neuropsychiatric symptoms (NPS) in patients with cognitive impairment (CI). METHODS: This multicenter study with 1037 consecutive patients was conducted from December 2012 to December 2019. 18 F-FDG PET and clinical/demographic information, NPS assessments were recorded and analyzed to explore the associations between hypometabolic patterns and clinical features by correlation analysis and multivariable logistic regression models...

Aggregates of the tau protein are a well-known hallmark of several neurodegenerative diseases, collectively referred to as tauopathies, including frontal temporal dementia and Alzheimer's disease (AD). Monitoring the transformation process of tau from physiological monomers into pathological oligomers or aggregates in a high-throughput, quantitative manner and in a cellular context is still a major challenge in the field. Identifying molecules able to interfere with those processes is of high therapeutic interest...