AbstractBackgroundIdentification of patients with familial dementia is important as this may explain disease in families, raises the possibility of predictive testing for relatives and enables participation in trials. Previously proposed clinical criteria to offer genetic testing based on diagnosis, age, and familial history do not capture the diversity of clinical presentation of patients. We aimed to develop data‐derived clinical criteria and prospectively validated these by applying them in a memory clinic.MethodIn a 2,5‐year period (1‐1‐2010 until 30‐6‐2012) 1138 patients visited the Alzheimer Center Amsterdam and underwent routine diagnostic work‐up (van der Flier et al 2018). The average age of individuals was 62 years, 41% of the patients being female. Patients provided DNA for research purposes, which allowed us to test 1022 (90%) of the patients for variants in 54 dementia related genes (exome sequencing), APP duplications and C9orf72‐repeat expansions. Data driven clinical criteria for genetic testing were formulated to optimally identify carriers of a causal mutation. Subsequently, we offered genetic testing according to the new clinical criteria to all patients in the Alzheimer Center Amsterdam for 1 year (9‐2021 to 9‐2022).ResultWe identified genetic mutations causing dementia in 34 patients, which accounted for 3.3% of all patients. Previous criteria would have selected 23% of these patients for testing and identified 47% of the mutation carriers. We formulated optimized clinical criteria(as shown in Figure 1), that would have identified 88% of mutation carriers(30/34 carriers) in 26% of all patients. This efficient selection was prospectively validated in 2021. A 149 out of 517 patients(29%) were eligible for genetic testing based on the new criteria. Of these 90 patients(60.4%) opted for testing and 59(39.6%) declined testing or clinicians decided against offering the test. We found 12 out of 90(13%) to carry a mutation. This confirms the efficient selection as 10 mutation carriers were anticipated in the tested group based on our research data.ConclusionData driven clinical criteria for genetic testing efficiently selected individuals with genetic dementia in a real‐life implementation. Memory clinics can adopt these clinical criteria to offer genetic testing to the patients most likely to benefit.