Major or Mild Neurocognitive Disorder Due to Alzheimer’s Disease 613
agnosis is approximately 10 years, reflecting th e advanced age of the majority of individ-
uals rather than the course of the disease; some individuals can live with the disease for as
long as 20 years. Late-stage individuals are eventually mute and bedbound. Death most
commonly results from aspiration in those who survive through the full course. In mild
NCD due to Alzheimer’s disease, impairments increase over time, and functional status
gradually declines until symptoms reach the threshold for the diagnosis of major NCD. 
The onset of symptoms is usually in the eighth and ninth decades; early-onset forms
seen in the fifth and sixth decades are often related to known causative mutations. Symp-
toms and pathology do not differ markedly at different onset ages. However, younger in-
dividuals are more likely to survive the full course of the disease, while older individuals
are more likely to have numerous medical co morbidities that affect the course and man-
agement of the illness. Diagnostic complexity is  higher in older adults because of the in-
creased likelihood of comorbid me dical illness and mixed pathology.
Risk and Prognostic Factors
Environmental. Traumatic brain injury increases risk  for major or mild NCD due to Alz-
heimer’s disease.
Genetic and physiological. Age is the strongest risk factor for Alzheimer’s disease. The
genetic susceptibility polymorphism apolipoprotein E4 increases risk and decreases age
at onset, particularly in homozygous individu als. There are also extremely rare causative
Alzheimer’s disease genes. Individuals with Down’s syndrome (trisomy 21) develop Alz-
heimer’s disease if they survive to midlife. Multiple vascular risk factors influence risk for