Background/Purpose: Sporadic early-onset Alzheimer disease (sEOAD) and its visual variant, posterior cortical atrophy (PCA), have a disease onset at less than 65 years of age with no familial aggregation. The etiology and genetic basis of these diseases remain poorly understood. Our study aimed to identify additional mutations or variants associated with sEOAD and PCA and to further examine their genetic and phenotypic spectrums. Methods: We performed whole-exome sequencing and analyzed the clinical and neuroimaging features of mutation carriers with 29 patients having sEOAD and 25 having PCA. Results: Nine rare damaging variants were identified in 4 patients with sEOAD and 3 with PCA. A novel mutation (p.A136V) in PSEN1 was identified in a patient with sEOAD and a likely pathogenic variant (p.M239T) was identified for PSEN2 in a patient with PCA. In addition, 7 rare damaging variants were detected in other genes related to neurodegenerative diseases. The patient carrying the PSEN1 p.A136V mutation presented with typical clinical and imaging features of sEOAD, and the PCA patient with the PSEN2 p.M239T mutation presented with visuospatial impairment as the initial symptom. Conclusion: Our study expands the PSEN1 mutation spectrum of sEOAD and highlights the importance of screening PSEN1 and/or PSEN2 mutations in PCA patients.

Background: A mobile cognition scale for community screening in cognitive impairment with rigorous validation is in paucity. We aimed to develop a digital scale that overcame low education for community screening for mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and AD. Methods: A mobile cognitive self-assessment scale (CogSAS) was designed through the Delphi process, which is feasible for the older population with low education. In Phase 1, 518 clinically diagnosed participants were subjected to optimise the items. In Phase 2, the scale was validated in 358 participants with cognitively unimpaired and 396 participants of clinically diagnosed MCI and dementia for reliability, validity and diagnostic accuracy. In Phase 3, specificity and sensitivity were tested for biologically diagnosed participants of 38 with cognitively unimpaired and 45 with MCI and dementia due to AD according to the amyloid, tau, neurodegeneration classification system. Results: The CogSAS was a three-task mobile scale testing memory and executive function. In Phase 2, the internal consistency was 0.81, and the test–retest reliability was 0.82. The construct validity was 0.74, and the criterion validity was 0.77. The sensitivity and specificity for discriminating clinically diagnosed participants with MCI and dementia from cognitively unimpaired were 0.90 and 0.67, respectively. For discriminating biologically diagnosed MCI and dementia due to AD from cognitively unimpaired, the sensitivity and specificity were 1.00 and 0.78, respectively. Conclusions: The CogSAS has good reliability, validity and feasibility, showing a high sensitivity and specificity both in the community and the clinic, identifying biologically diagnosed MCI and dementia due to AD.