The present disclosure is based on the identification of biomarkers of combined genetic variants and imaging measurements, in predicting faster decline in cognitive measures and brain glucose metabolism in populations with Alzheimer's disease or those susceptible to developing Alzheimer's disease. The present disclosure provides a method of treating a patient with Alzheimer's disease (AD) or a subject susceptible to developing AD, comprising: (a) assaying a sample obtained from an early-stage AD patient or a subject susceptible to developing AD for the presence of a brain-derived neurotrophic factor (BDNF) gene mutation and/or a protein tyrosine phosphatase receptor-type, Z polypeptide 1 (Ptprz1) gene mutation; (b) determining whether the patient or subject is positive for brain amyloid-beta (Αβ), wherein the presence of brain Αβ in combination with the BDNF gene and/or Ptprz1 gene mutation correlates with a prediction of rapid cognitive decline; and (c) treating the patient or subject with early and aggressive therapy appropriate to treat AD with rapid cognitive decline.
GENETIC AND IMAGE BIOMARKERS ASSOCIATED WITH DECLINE IN COGNITIVE MEASURES AND BRAIN GLUCOSE METABOLISM IN POPULATIONS WITH ALZHEIMER'S DISEASE OR THOSE SUSCEPTIBLE TO DEVELOPING ALZHEIMER'S DISEASE