The earliest signs of Alzheimer's disease

Insufficient clarity of definition of the clinical features in the earliest stages of developing Alzheimer's disease (AD) has impeded the execution of clinical and biologic studies into this major public health problem. Defining the earliest signs of a disease with such an insidious onset can prove to be a most elusive task, particularly in a disease whose very nature renders the patients' self-report unreliable. We therefore administered a structured interview to the close family caregivers of 83 patients with probable AD, in order to investigate the earliest perceived signs of illness in the patients. In 44 (53%) of patients, the earliest objective sign of change was not memory impairment. The initial sign of change was of a psychiatric type in 27 (32.5%); of a neurologic type in nine (10.9%); and of a noncoping type in eight (9.6%). Such nonmemory signs, as perceived by caregivers, preceded objective memory impairment by a mean of 1.8 years. In 39 patients (47%), memory impairment was the initial perceived sign of illness. These findings suggest that the earliest clinical manifestations of AD may, in many cases, significantly predate objective signs of memory impairment.