The major challenges of the “brain disorders” field – dementia, schizophrenia, other neuropsychiatric disorders – are that these are defined by clinical phenotypes whose underlying biology is poorly understood. There is great variability in definition, prognosis, trajectory, and treatment response indicating that the next step is defining subgroups by combining clinical and biologic information at the level of the individual. These challenges are especially relevant and urgent in the case of dementia and related disorders.