More Than a Senior Moment

Rita Philip and her daughter were among my first participants in the revolution of how we diagnose Alzheimer’s disease. I first met them in the spring of 2012. While Mrs. Philip underwent cognitive testing, her daughter and I took our catty-corner seats at the small desk in my examination room at the Memory Center. I asked, “What’s the problem? How can I help you?” She looked at me like she was about to cry, then looked at the floor and said, “I’d like to make sure my mom doesn’t have something neurological.”

Her mother, a retired homemaker, was aware of cognitive changes, though she minimized them. “Senior moments,” she explained. “What do you expect? I’m seventy-eight.” And perhaps she was right. Whatever was going on was mild. Her daughter told me her mother needed more time to complete complex day-to-day activities, like preparing a family dinner. She was also making mistakes, such as forgetting to take medications, but she was catching them. Her cognitive testing showed scores that were low, but for a homemaker with two years of college (she left school to marry and raise a family), the scores were within the range of normal.

Her cognitive changes seemed to be more in degree than in kind. She wasn’t doing as well as she once did, but she wasn’t abnormal. She certainly did not have dementia. Both wanted to know what caused her mild cognitive problems. Was it just aging or, as her daughter asked, “Is there something neurological?” New brain scans and a revolutionary new way of thinking about Alzheimer’s disease allowed me to answer her question definitively. Her mother did have something neurological. She had Alzheimer’s disease, but she did not have dementia.

The science that allowed me to diagnose her with Alzheimer’s disease without dementia can be traced back to a spring afternoon in 1984 when the psychologist Bob Ivnik bumped into Len Kurland while crossing the intersection of Second Street and Fourth Avenue in Rochester, Minnesota.

“It was bright, sunny, and clear, a nice day. I was walking to a meeting when Len Kurland pulled me aside at an intersection and said very quickly: ‘I wanted to let you know I submitted a grant and put your name on it.’ I was like, OK, whatever, and just kept walking,” Bob Ivnik recalled. Ivnik, 36 years old, was just six years into his job as the Mayo Clinic’s first neuropsychologist. A dedicated clinician with a calm but serious demeanor, his typical day was spent helping physicians care for patients with epilepsy. Caring for patients was his dream job. He had no desire to do research.

“I wasn’t happy when I found out that Len had me on his grant. I thought that wasn’t my interest. I felt like I was being pulled into something I didn’t want to do, but you can’t say no to Len Kurland at the Mayo.” Looking back, he came to understand how singularly important that afternoon was not only for him but also for all aging people. He would become part of a team of researchers who, after 15 years of work, published one of the most cited papers in the history of Alzheimer’s. Its results upended how doctors talk about normal aging and Alzheimer’s disease.

At Mayo, Leonard Kurland set up the Rochester Epidemiology Project for epidemiologists to understand the patterns and predictors of diseases. His reputation was of a take-charge autocrat. Facing an impossible eleventh-hour deadline to submit a grant application on time to the National Institutes of Health via the US postal system, Kurland, a licensed pilot, flew the application from Rochester to Washington, DC. The grant Kurland had mentioned in passing to Ivnik was an ambitious, first-of-its-kind application to the National Institute on Aging’s recently formed Alzheimer’s disease research program. Leveraging the resources of the Rochester Epidemiology Project, they would identify older adults with well-characterized cognitive abilities, divide them into two groups—those with and those without Alzheimer’s disease—and then follow these hundreds of people for years. The data would allow answers to simple but foundational questions: How many people have Alzheimer’s disease? What are the risk factors for getting it? How fast does it progress? It would also discover better instruments to diagnose patients.

The Alzheimer’s Disease Patient Registry (ADPR) was unfolding on perfect soil. This was an unmistakably unique opportunity to conduct a study of the aging brain, to count and compare the characteristics of persons without cognitive impairment and persons with dementia. As long as the team stuck to their methods and measures, the conclusions they would make about the epidemiology of aging, cognition, and Alzheimer’s disease could speak to the nation. But first Bob Ivnik had to be inspired to make the best of what he felt was a bad situation.

For Ivnik, the ADPR was a distraction. He wanted to take care of patients. “I really enjoyed the testing and using objective measurements to make behavioral and cognitive predictions and to help with diagnosis.” And yet, as he reflected on the clinical practice of psychology that he so enjoyed, he realized psychology was deeply flawed. The tests he used to measure older adults’ memory really couldn’t answer a patient’s fundamental question: “Doctor, am I normal?” “I realized that the normative basis for almost all of our cognitive tests above the age of seventy-four did not exist.” The Wechsler tests, for example, “the absolute pinnacle of cognitive testing,” lacked any data to say whether an older adult’s score was normal. Ivnik experienced a change of heart about the ADPR. It wasn’t a distraction. It was instead an amazing opportunity.