TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions.

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease.

Medial temporal lobe contributions to intra-item associative recognition memory in the aging brain.

Aging is associated with a decline in episodic memory function. This is accompanied by degradation of and functional changes in the medial temporal lobe (MTL) which subserves mnemonic processing. To date no study has investigated age-related functional change in MTL substructures during specific episodic memory processes such as intra-item associative memory.

New criteria for frontotemporal dementia syndromes: clinical and pathological diagnostic implications.

Objective: To assess the impact of new clinical diagnostic criteria for frontotemporal dementia (FTD) syndromes, including primary progressive aphasias (PPA), on prior clinical diagnosis and to explore clinicopathological correlations.

Methods: 178 consecutive neuropathologically ascertained cases initially diagnosed with a FTD syndrome were collected through specialist programmes: the Cambridge Brain Bank, UK, and Sydney Brain Bank, Australia. 135 cases were reclassified using the revised diagnostic criteria into behavioural variant (bvFTD), semantic variant PPA (sv-PPA), non-fluent/agrammatic variant PPA (nfv-PPA) and logopenic variant PPA (lv-PPA).

Giving words new life: generalization of word retraining outcomes in semantic dementia.

Background: Anomia is a common and debilitating symptom for many dementia sufferers, but is particularly marked in patients with the semantic variant of primary progressive aphasia, semantic dementia (SD). Recent studies have demonstrated that through cognitive training these patients can re-learn the names of objects, but it remains unclear whether this translates to improved use of these relearned words in contexts other than picture naming.

Methods: Five SD patients completed a 2-month, online word training program and were assessed pre- and post-intervention on picture naming and spoken word-picture-matching plus two novel ecological tasks: video description and responses to verbal requests.

Neuropsychiatric changes precede classic motor symptoms in ALS and do not affect survival.

Objectives: To investigate patient susceptibility to neuropsychiatric symptoms in the context of progression of more classic motor symptoms in amyotrophic lateral sclerosis (ALS) and to examine the impact of neuropsychiatric symptoms on survival.

Methods: The study cohort consisted of 219 patients with ALS (limb onset = 159; bulbar onset = 60), with neuropsychiatric symptoms measured using the Motor Neuron Disease Behavioural Scale and more classic ALS symptoms assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. For detection of symptom susceptibility (neuropsychiatric vs classic motor), a Rasch analysis was applied (n = 219).

Memory and orientation in the logopenic and nonfluent subtypes of primary progressive aphasia.

Memory and orientation were investigated as predictors of underlying Alzheimer's disease (AD) pathology in patients with logopenic (lv) and non-fluent (na) variants of primary progressive aphasia (PPA). Memory and orientation scores from Addenbrooke's Cognitive Examination were compared between 26 lv-PPA, 29 na-PPA, 59 AD, and 90 controls using analysis of variance. Forty-five patients underwent Pittsburgh compound B (PiB) positron emission tomography scans.

Neural substrates of episodic memory dysfunction in behavioural variant frontotemporal dementia with and without C9ORF72 expansions.

The recently discovered hexanucleotide repeat expansion, C9ORF72, has been shown to be among the most common cause of familial behavioural variant frontotemporal dementia (bvFTD) and to be present in a significant minority of apparently sporadic cases. While mounting evidence points to prominent episodic memory dysfunction in bvFTD cases, recent reports have also suggested an amnestic profile in C9ORF72 mutation carriers. No study to date, however, has formally characterised the extent to which episodic memory is impaired in C9ORF72 mutation versus sporadic cases, or the underlying neural substrates of such deficits.

Money for nothing - Atrophy correlates of gambling decision making in behavioural variant frontotemporal dementia and Alzheimer's disease.

Neurodegenerative patients show often severe everyday decision making problems. Currently it is however not clear which brain atrophy regions are implicated in such decision making problems. We investigated the atrophy correlates of gambling decision making in a sample of 63 participants, including two neurodegenerative conditions (behavioural variant frontotemporal dementia - bvFTD; Alzheimer's disease - AD) as well as healthy age-matched controls.

Distribution of pathology in frontal variant Alzheimer's disease.

Atypical presentations of Alzheimer's disease (AD) have been described, including a "frontal" variant (fvAD), which presents with personality change and executive dysfunction similar to that seen in behavioral variant frontotemporal dementia (bvFTD). This clinical variation is thought to reflect the regional distribution of pathology, although few reports include autopsy confirmation. We compared three clinicopathological groups matched for age at diagnosis and disease duration; those with possible bvFTD who at autopsy had only AD (fvAD), those with typical AD clinically and pathologically, and those with typical clinical bvFTD confirmed pathologically.

Circadian misalignment and sleep disruption in mild cognitive impairment.

Background: While it is evident that Alzheimer's disease is associated with disturbed sleep and circadian rhythms, the extent to which such changes are evident in older people 'at risk' of developing dementia is unknown.

Objective: In this study, we aimed to determine whether patients with mild cognitive impairment (MCI) demonstrated significant alterations in the timing of melatonin secretion onset and amount, as well as sleep architecture.

Methods: Thirty patients with MCI and 28 age-matched controls underwent psychiatric, medical, and neuropsychological assessment, followed by overnight polysomnography and dim light melatonin onset assessment.

Differential prospective memory profiles in frontotemporal dementia syndromes.

Background: Prospective memory (PM) is the ability to remember to execute an intended action either at a future time (Time-based PM) or when a specific event occurs (Event-based PM). Previous studies demonstrate impaired PM in Alzheimer's disease (AD); however, the status of PM in frontotemporal dementia (FTD) remains unknown.

Objective: To examine PM performance and its associated cognitive mechanisms, in two subtypes of FTD: semantic dementia (SD) and the behavioral variant of FTD (bvFTD), in comparison with matched AD and control participants.

Towards a clearer definition of logopenic progressive aphasia.

Logopenic progressive aphasia is the most recently described clinical variant of primary progressive aphasia (PPA), defined by impairment of lexical retrieval and sentence repetition. Unlike other PPA variants, the logopenic variant of PPA (lv-PPA) is commonly associated with Alzheimer's disease (AD), a fact that is relevant to the selection of patients for clinical trials and disease-modifying therapies. Despite the straightforward definition and coherent pathological association, the existence of lv-PPA has been challenged, as its distinction from AD or other PPA variants can be difficult.

Validation of the Addenbrooke's Cognitive Examination III in frontotemporal dementia and Alzheimer's disease.

Background/aims: The aims of this study were to validate the newly developed version of the Addenbrooke's Cognitive Examination (ACE-III) against standardised neuropsychological tests and its predecessor (ACE-R) in early dementia.

Methods: A total of 61 patients with dementia (frontotemporal dementia, FTD, n = 33, and Alzheimer's disease, AD, n = 28) and 25 controls were included in the study.

Results: ACE-III cognitive domains correlated significantly with standardised neuropsychological tests used in the assessment of attention, language, verbal memory and visuospatial function.

Emotion processing deficits distinguish pure amyotrophic lateral sclerosis from frontotemporal dementia.

Amyotrophic lateral sclerosis (ALS) is a multisystem disease that overlaps with frontotemporal dementia (FTD). Although FTD patients exhibit prominent deficits in emotion perception and social cognition, these domains have received relatively little attention in ALS. Moreover, direct comparisons between ALS and FTD on emotion processing tasks remain lacking.

Oligonucleotide tagging for copper-free click conjugation.

Copper-free click chemistry between cyclooctynes and azide is a mild, fast and selective technology for conjugation of oligonucleotides. However, technology for site-specific introduction of the requisite probes by automated protocols is scarce, while the reported cyclooctynes are large and hydrophobic. In this work, it is demonstrated that the introduction of bicyclo[6.

When one loses empathy: its effect on carers of patients with dementia.

The effects of empathy loss in frontotemporal dementia (FTD) and Alzheimer disease (AD) on carer symptomatology were investigated. Carers of patients with 2 clinical subtypes of FTD (behavioral-variant FTD [bvFTD] = 18; semantic dementia [SD] = 14) and AD (n = 18) completed the Interpersonal Reactivity Index (IRI), a standardized questionnaire of empathy as well as a measure of perceived burden (Zarit Burden Interview) and the quality of the marital relationship (Intimate Bond Measure). Patient ratings were also obtained on the IRI.

The orbitofrontal cortex is involved in emotional enhancement of memory: evidence from the dementias.

The enhancing effect of emotion on subsequent memory retrieval is well established. Patients with frontotemporal dementia show profound emotion processing difficulties, yet the extent to which such deficits attenuate emotional enhancement of memory remains unknown. Here, we studied the intersection between emotion and memory using a visual forced-choice recognition test for negative and neutral stimuli in 34 patients with frontotemporal dementia compared with 10 patients with Alzheimer's disease and 15 control subjects.

Discrete Neural Correlates for the Recognition of Negative Emotions: Insights from Frontotemporal Dementia.

Patients with frontotemporal dementia have pervasive changes in emotion recognition and social cognition, yet the neural changes underlying these emotion processing deficits remain unclear. The multimodal system model of emotion proposes that basic emotions are dependent on distinct brain regions, which undergo significant pathological changes in frontotemporal dementia. As such, this syndrome may provide important insight into the impact of neural network degeneration upon the innate ability to recognise emotions.

Endogenous progesterone levels and frontotemporal dementia: modulation of TDP-43 and Tau levels in vitro and treatment of the A315T TARDBP mouse model.

Frontotemporal dementia (FTD) is associated with motor neurone disease (FTD-MND), corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). Together, this group of disorders constitutes a major cause of young-onset dementia. One of the three clinical variants of FTD is progressive nonfluent aphasia (PNFA), which is focused on in this study.

Identifying cognitive and demographic variables that contribute to carer burden in dementia.

Background/aims: Carer burden has been associated with other carer-reported factors (e.g. depression), but less is known about the influence of more independent variables.

Common and unique gray matter correlates of episodic memory dysfunction in frontotemporal dementia and Alzheimer's disease.

Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type.

Early saccades in amyotrophic lateral sclerosis.

Our objective was to correlate saccadic abnormalities, including early saccades, in patients with amyotrophic lateral sclerosis (ALS) with measures of motor and functional impairment. A portable saccadometer was used to record saccades in ALS patients and control subjects. The linear approach to threshold with ergodic rate model was used to characterize saccades, including sub-populations of early saccades.

Episodic future thinking is impaired in the behavioural variant of frontotemporal dementia.

Remembering the past and imagining the future are complex endeavours proposed to rely on a core neurobiological brain system. In the behavioural variant of frontotemporal dementia (bvFTD), regional patterns of brain atrophy affect medial prefrontal and temporal cortices of this core network. While autobiographical memory impairments have been documented in bvFTD, it remains unknown whether the ability to imagine future events is also compromised.

Clinical profile of PiB-positive corticobasal syndrome.

Background: Corticobasal syndrome (CBS) is a multifaceted neurodegenerative disorder characterized by a combination of motor and cognitive deficits. Several different pathological entities, including Alzheimer's pathology, have been described in association with CBS. The present study aimed to establish clinical, neuropsychological, and neuroimaging features that could be useful in the distinction of CBS due to AD pathology from other CBS cases in life based on [(11)C] Pittsburgh Compound B positron emission tomography (PiB-PET) status.