Alzheimer's: Treating Anxiety Slows Decline

Alzheimer ’s disease (AD) has a long preclinical phase in which pathology develops years or decades before clinical symptoms. In study in JAMA Psychiatry, Robert Pietrzak, PhD, MPH and colleagues report that depression, anxiety and cognitive decline are associated with presence of Amyloidβ but that patients will benefit if their depression and anxiety are treated.

“Given that there is currently no standard anti-amyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD,” the team wrote.

In the multicenter study a cohort of 333 healthy adult patients were recruited and 25% were assessed with brain scans to detect Amyloidβ. The subjects were age 60 and up. About half had memory complaints. They also got neuropsychological evaluations. One goal was to see if the presence of Amyloidβ was related to the onset and intensity of depression and anxiety. The hope was that if that turned out to be the case, ameliorating those mental health conditions with lessen cognitive decline.

In tracking the patients, the team found that even when patients had Amyloidβ those with low anxiety developed less cognitive decline than did a group with Amyloidβ and high anxiety.

“Elevated anxiety symptoms may exacerbate Amyloidβ related cognitive impairment by increasing endogenous levels of glucocorticoids, which consequently damages brain regions such as the hippocampus, and result in more pronounced decline in memory and related cognitive functions over time,” they wrote. They also cited animal studies on Amyloidβ toxicity that linked the protein to changes in the hypothalamic-pituitary-adrenal axis regulation and to increases in glucocorticoids.

Anxiety can negatively affect encoding and retention of verbal information, as well as other cognitive processes like executive function, they wrote.

Even subthreshold anxiety may exacerbate Amyloidβ-related cognitive decline, they said.

Among the study’s limitations, they noted, is the possibility that other biological factors such as neuronal loss, gliosis, and hyperphosphory-related tau protein aggregates are to blame for cognitive decline in preclinical AD.