Background FAD is most commonly caused by mutations in the PSEN1 and APP genes. We explored the associated clinical phenotype through analysis of the cohort of symptomatic individuals from FAD families studied at our centre.

Methods Clinical history and neurological examination findings were recorded for 95 individuals with FAD secondary to mutations in PSEN1 (n=66) or APP (n=29). These were reviewed to ascertain the earliest cognitive symptoms and presence of additional neurological features during the disease.

Results Memory impairment was the earliest cognitive symptom in 97% of APP and 83% of PSEN1patients. The presenting symptom in the remainder of the APP group was dyscalculia. In the PSEN1 group it was behavioural change in 11%, language impairment in 3% and dyscalculia in 3%. 24% of APP patients had myoclonus and 28% had seizures. In the PSEN1 cohort, 50% had myoclonus, 20% had seizures, 18% had pyramidal signs, usually spastic paraparesis, 15% had extrapyramidal signs and 3% had cerebellar signs.

Conclusion Amnestic presentations occurred in the majority, particularly those with APP mutations. Initial symptoms could, however, relate to behaviour, language or calculation skills. Myoclonus and seizures occurred relatively frequently with both mutations. Spastic paraparesis and extrapyramidal signs were not uncommon in the PSEN1 group. FAD should be considered in young patients with dementia and additional neurological features, particularly if the family history is censored.