Frontotemporal dementia is an umbrella clinical term that encompasses a group of neurodegenerative diseases characterised by progressive deficits in behaviour, executive function, or language. Frontotemporal dementia is a common type of dementia, particularly in patients younger than 65 years. The disease can mimic many psychiatric disorders because of the prominent behavioural features. Various underlying neuropathological entities lead to the frontotemporal dementia clinical phenotype, all of which are characterised by the selective degeneration of the frontal and temporal cortices. Genetics is an important risk factor for frontotemporal dementia. Advances in clinical, imaging, and molecular characterisation have increased the accuracy of frontotemporal dementia diagnosis, thus allowing for the accurate differentiation of these syndromes from psychiatric disorders. As the understanding of the molecular basis for frontotemporal dementia improves, rational therapies are beginning to emerge. Copyright © 2015 Elsevier Ltd. All rights reserved.

It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-microm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V-VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I-II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.

The construct of mild cognitive impairment (MCI) has been proposed to identify patients at risk of developing Alzheimer's disease (AD) in the pre-clinical stage. Although subjects with MCI have an increased risk of progressing to dementia, most remain stable or return to normality. The new criteria for diagnosing prodromal AD assume that, to increase the predictive value of the MCI, in addition to a defect of delayed recall there must also be the presence of abnormal biomarkers, investigating structural and molecular neuroimaging and cerebrospinal fluid (CSF) analysis of amyloid-β or tau proteins. Although acknowledging that the use of CSF degeneration biomarkers is advisable not only for research, but also for clinical purposes, the present review is centered upon the neuropsychological markers of conversion to AD, which are equally clinically important. In particular, results of this review suggest the following: (a) measures of delayed recall are the best neuropsychological predictors of conversion from MCI to AD; (b) memory tests providing controlled encoding and cued recall are not necessarily better predictors than free recall tests; (c) stringent cut-off points are necessary to increase the specificity of these predictors; (d) multi-domain amnestic MCI patients are the best candidates for clinical trials, but not for treatment with disease-modifying drugs; and (e) not only episodic but also semantic memory is significantly impaired in patients who will convert to AD. These data and the underlying neural mechanisms will be discussed, trying to distinguish results obtained in MCI patients from those obtained in a pre-MCI stage of the AD progression.

Attempts to identify cognitive markers of a preclinical phase of Alzheimer's disease (AD) have yielded inconsistent findings. The problem may stem in part from methodologies that are insensitive to potential subgroups within the at-risk, preclinical AD population (PCAD). The present study investigated the utility of asymmetric cognitive profiles in identifying individuals at risk for AD. Twenty elderly adults who were later diagnosed with AD (PCAD) and 20 matched control participants were compared on measures of cognitive asymmetry derived from difference scores on tests of verbal and visuospatial ability. Although both groups performed similarly on the individual tests, comparisons using difference scores revealed significantly larger discrepancies between naming and visuoconstruction skills in the PCAD group. The PCAD group also had a higher frequency of asymmetric cognitive profiles relative to a normative group.

The aim of this study was to assess the ability of Neuropsychiatric Inventory (NPI) scale profiles to differentiate between distinct frontotemporal dementia (FTD) subtypes.The NPI was used to assess 311 older patients who had been clinically diagnosed with FTD. FTD subtypes included behavioural variant FTD (bvFTD, n = 121), primary progressive aphasia (semantic variant (n = 69), non-fluent agrammatic variant (n = 31), and logopenic variant (n = 0)), FTD-motor neuron disease (n = 4), progressive supranuclear palsy (n = 43), and corticobasal syndrome (n = 43). Total NPI score and scores for each NPI item were correlated across the distinct FTD subtypes.Patients with bvFTD showed significantly greater impairment on their total NPI score than patients with corticobasal syndrome (P < 0.001), non-fluent agrammatic variant primary progressive aphasia (P < 0.001), progressive supranuclear palsy (P = 0.002), and semantic variant primary progressive aphasia (P = 0.010). Aggressiveness, euphoria, apathy, disinhibition, irritability, aberrant motor behaviours, and appetite disturbance were significantly higher in bvFTD than in the other subgroups. The lowest NPI scores were generally shown among those with CBS. However, NPI total and specific item values overlapped among the subtypes.Patients with bvFTD showed significantly greater neuropsychiatric dysfunction than those with the other FTD subtypes, as measured by the NPI scale. In contrast, patients with corticobasal syndrome had a comparatively healthier profile. Therefore, differential diagnosis among the FTD subtypes may be guided by the NPI, although the subtype is unlikely to be confirmed on the basis of NPI alone.© 2018 Japanese Psychogeriatric Society.

We sought to identify the cognitive tests that best discriminate between Alzheimer's disease (AD) and frontotemporal dementia (FTD). A comprehensive search of all studies examining the cognitive performance of persons diagnosed with AD and FTD, published between 1980 and 2006, was conducted. Ninety-four studies were identified, comprising 2936 AD participants and 1748 FTD participants. Weighted Cohen's d effect sizes, percentage overlap statistics, confidence intervals and fail-safe Ns were calculated for each cognitive test that was used by two or more studies. The most discriminating cognitive tests were measures of orientation, memory, language, visuomotor function and general cognitive ability. Although there were large and significant differences between groups on these measures, there was substantial overlap in the scores of the AD and FTD groups. Age, education, years since diagnosis and diagnostic criteria did not significantly contribute to the group differences. Given the large overlap in the test performance of persons diagnosed with AD and FTD, cognitive tests should be used cautiously and in conjunction with a medical history, behavioural observations, imaging and information from relatives when making differential diagnoses.