Alzheimer’s May Start Sooner for People With Anxiety, Depression History

A history of either anxiety or depression was inversely associated with the age when Alzheimer’s disease started, a retrospective analysis suggested.

People with Alzheimer’s disease who had a past diagnosis of anxiety were 3 years younger than other Alzheimer’s patients when they developed the disease, reported Zachary Miller, MD, of the University of California San Francisco (UCSF), and co-authors.

Patients with a history of depression were 2 years younger at Alzheimer’s onset, they said in an abstract released in advance of the 2021 American Academy of Neurology annual meeting.

The findings were based on 1,500 Alzheimer’s disease patients from the UCSF Memory and Aging Center who were screened for past psychiatric disorders, including depression, anxiety, bipolar disorder, schizophrenia, and post-traumatic stress disorder (PTSD). Researchers evaluated typical Alzheimer’s risk factors — hypertension, hyperlipidemia, diabetes, education, and APOE4 status — as well as novel Alzheimer’s-associated factors like left handedness, learning disabilities, autoimmune diseases, and seizure history.

“We are continuing to delve deeper into these findings,” Miller said. “We have reason to believe that we have validated our core results in a very large external database of Alzheimer’s patients from the National Alzheimer’s Coordinating Center, which we will hopefully be discussing in greater depth during our presentation” at the AAN annual meeting, he told MedPage Today.

It’s “relatively well established that certain psychiatric conditions, especially depression and anxiety, are associated in some way with cognitive decline and possibly dementia,” noted Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association in Chicago, who was not involved with the study.

“Questions remain, however, about whether the cognitive changes are leading to the psychiatric conditions, or the psychiatric conditions are contributing to the cognitive changes,” Sexton told MedPage Today. “It is likely that both are to some extent true, but more research is needed to clarify these relationships.”

Of the Alzheimer’s patients in the UCSF study, 43.3% had a history of depression, 32.3% had anxiety, 1.2% had bipolar disorder, 1% had PTSD, and 0.4% had schizophrenia. Patients with depression or anxiety were significantly younger at age at Alzheimer’s onset by 2.1 and 3.0 years, respectively, compared with those without (P<0.001).

Reductions in age at Alzheimer’s onset doubled with each additional psychiatric diagnosis: a history of one psychiatric disorder was linked to Alzheimer’s starting 1.5 years earlier, two psychiatric disorders to 3.3 years earlier, and three or more psychiatric disorders to 7.3 years earlier (P<0.001).

People with depression or anxiety history were more likely to be women and had fewer typical Alzheimer’s disease risk factors. The group with past depression diagnoses also had a significantly higher prevalence of autoimmune diseases (P=0.01). The anxiety cohort was more likely to have a history of seizures (P=0.002).

The findings suggest that psychiatric disorders “each possess unique and additive effects on Alzheimer’s disease pathophysiology,” the researchers observed.

“While this association between depression and autoimmune disease, and seizures and anxiety is quite preliminary, we hypothesize that the presentation of depression in some people could possibly reflect a greater burden of neuroinflammation,” Miller said. “The presence of anxiety might indicate a greater degree of neuronal hyperexcitability, where the networks in the brain are overstimulated, potentially opening up new therapeutic targets for dementia prevention.”

A limitation of the study is that data were obtained from a tertiary specialty memory care center by retrospective chart review.

Last Updated February 24, 2021