Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behavior, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (MAPT), granulin precursor (GRN), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72- SMCR8complex subunit (C9orf72) while mutations in other genes such as optineurin (OPTN) have rarely been reported. Mutations in OPTN have been reported mostly in familial and sporadic cases of ALS, or in rare cases of FTD-ALS, but not in association with pure or predominant FTD and/or parkinsonian phenotype. Here, we report for the first time, a family from the Philippines with four members harboring a novel frameshift insertion at OPTN (Chr 10:13166090 G>GA) p.Lys328GluTer11, three of whom presented with FTD-related phenotypes. Additionally, one sibling heterozygous for the frameshift insertion had a predominantly parkinsonian phenotype resembling corticobasal syndrome, but it remains to be determined if this phenotype is related to the frameshift insertion. Notably, none of the affected members showed any evidence of motor neuron disease or ALS at the time of writing, both clinically and on electrophysiological testing, expanding the phenotypic spectrum of OPTN mutations. Close follow-up of mutation carriers for the development of new clinical features and wider investigation of additional family members with further genetic analyses will be conducted to investigate the possibility of other genetic modifiers in this family which could explain phenotypic heterogeneity.
Data on the association between syphilis reactivity and dementia in memory clinic patients are scarce. We studied the prevalence of syphilis reactivity and investigated its association with dementia and markers of cerebrovascular disease (CeVD) and neurodegeneration. Data on age, gender, education, brain computed tomography scan findings and syphilis reactivity were obtained from patients who attended the National University Hospital memory clinics (February 2006-February 2016) and subjects from the community. Binary logistic regression models were used to investigate associations between syphilis reactivity and dementia, CeVD and neurodegeneration, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Of 1271 memory clinic patients eligible for the study, 57 (4.5%) were syphilis reactive, with the rate of syphilis reactivity higher in demented (44/745; 5.9%) compared to non-demented (13/526; 2.5%) patients ( p = 0.004) and non-demented community-based (21/872; 2.4%) subjects ( p < 0.001). Binary logistic regression showed a significant association between syphilis reactivity and dementia in memory clinic patients independent of demographic factors (odds ratio: 2.06; 95% CI: 1.02-4.17, p = 0.044). A significant association between syphilis reactivity and dementia was found in memory clinic patients. The mechanism of this association requires further research and may involve neuroinflammation.
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