53 ATN classification in subjective cognitive decline e-Box. Four participants with notable disease trajectories Two participants in A- profiles progressed to Alzheimer’s dementia. The first (age 76, female, MMSE 30) was initially classified as A-T+N- and showed progression of cognitive symptoms over a course of eight years. After eight years, CSF was repeated showing a decline in Abeta (from 1029 pg/ml to 697 pg/ml, below cut-off) and a rise in p-tau (from 77 pg/ml to 150 pg/ml). Repeated MRI showed progression of MTA 0 to MTA 1.5, and after 11 years to MTA 2. This indicates this person changed to biomarker profile A+T+N+ in the course of eight years. The other participant (age 63, male, MMSE 28) was initially classified as A-T+N+ and showed progression of symptoms over four years. After four years, a [11C]PIB-PET scan was amyloid positive. A repeated MRI showed progression of MTA 1.5 to MTA 2. This indicates this person changed to biomarker profile A+T+N+. Two participants in A-T-N- progressed to other types of dementia. The first (age 56, female, MMSE 27) showed progressive language and executive dysfunction over a course of seven years. Repeated MRI showed progression of MTA from 0 to 2, but also progression of (asymmetrical) global cortical atrophy. CSF and/ or PET imaging was not repeated. This participant was diagnosed with primary progressive aphasia (PPA) due to FTD. The other participant (age 64, male, MMSE 26) showed progression of behavioral symptoms over a course of five years. The diagnosis possible FTD was made, although the slow progression was atypical and other causes such as alcohol abuse could not be excluded. Repeated MRI and FDG-PET scans did not provide support for the diagnosis of FTD. Genetic testing showed no genetic predisposition for dementia. 2
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