The cause of Alzheimer's disease is poorly understood.[11] There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of APOE.[13][14] Other risk factors include a history of head injury, clinical depression, and high blood pressure.[1] The disease process is largely associated with amyloid plaques, neurofibrillary tangles, and loss of neuronal connections in the brain.[15] A probable diagnosis is based on the history of the illness and cognitive testing, with medical imaging and blood tests to rule out other possible causes.[5][16] Initial symptoms are often mistaken for normal brain aging.[11] Examination of brain tissue is needed for a definite diagnosis, but this can only take place after death.[17] Good nutrition, physical activity, and engaging socially are known to be of benefit generally in aging, and may help in reducing the risk of cognitive decline and Alzheimer's.[15]