Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders.

OBJECTIVE: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. METHODS: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects. RESULTS: We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study. CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.

Defining Neuropsychiatric Inventory scale differences across frontotemporal dementia syndromes.

AIM: The aim of this study was to assess the ability of Neuropsychiatric Inventory (NPI) scale profiles to differentiate between distinct frontotemporal dementia (FTD) subtypes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Frontotemporal dementia spectrum: first genetic screen in a Greek cohort.

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative syndromes associated with several causative and susceptibility genes. Herein, we aimed to determine the incidence of the most common causative dementia genes in a cohort of 118 unrelated Greek FTD spectrum patients. We also screened for novel possible disease-associated variants in additional 21 genes associated with FTD or amyotrophic lateral sclerosis. Pathogenic or likely pathogenic variants were identified in 16 cases (13.6%). These included repeat expansions in C9orf72 and loss-of-function GRN variants, and likely pathogenic variants in TARDBP, MAPT, and PSEN1. We also identified 14 variants of unknown significance in other rarer FTD or amyotrophic lateral sclerosis genes that require further segregation and functional analysis. Our genetic screen revealed a high genetic burden in familial Greek FTD cases (30.4%), whereas only two of the sporadic cases (3.5%) carried a likely pathogenic variant. A substantial number of familial cases still remain without an obvious causal variant, suggesting the existence of other FTD genetic causes besides those currently screened in clinical routine.