Alzheimer's pathology, not cognitive decline, drives neuropsychiatric
symptoms
Biomarkers of pathology associated with apathy, anxiety

Date:
March 16, 2022
Source:
Elsevier
Summary:
Alzheimer's disease (AD) eventually leads to severe cognitive
decline, but most affected individuals also develop distressing
neuropsychiatric symptoms. These earlier effects may be more
subtle and are not well understood; it remains unclear whether they
arise directly from AD pathology or secondarily as psychological
reactions due to the cognitive deficits. Now, a new study examines
the connections between biomarkers of AD's hallmark neuropathology,
cognition, and other neuropsychiatric symptoms.



FULL STORY ========================================================================== Alzheimer's disease (AD) eventually leads to severe cognitive decline,
but most affected individuals also develop distressing neuropsychiatric symptoms. These earlier effects may be more subtle and are not well
understood; it remains unclear whether they arise directly from AD
pathology or secondarily as psychological reactions due to the cognitive deficits. Now, a new study examines the connections between biomarkers
of AD's hallmark neuropathology, cognition, and other neuropsychiatric symptoms. The study appears in Biological Psychiatry, published by
Elsevier.


==========================================================================
The researchers, led by Oskar Hansson, MD, at Lund University in
Sweden, tested cerebrospinal fluid or blood plasma from 356 cognitively unimpaired older adults for levels of the proteins amyloid-beta (Ab)
and tau, which are thought to contribute to AD neurotoxicity, as well
as markers of neurodegeneration.

Strikingly, the presence of Ab was associated with increased anxiety
and apathy. Higher levels of apathy were also related to a more rapid
cognitive decline.

"Most importantly, this study signals that certain neuropsychiatric
symptoms such as apathy and anxiety develop predominantly due
to underlying AD-related pathology and not due to the concomitant
cognitive impairment," said Maurits Johansson, MD, lead author of the
study. "It seems reasonable that neuropsychiatric symptoms would arise
from neuropathology just as cognitive deficits do, especially because
AD ultimately affects large areas of the brain," he added.

The study did not exclude a role for cognitive impairment altogether. For example, in one of the statistical analyses, cognitive decline slightly
but significantly mediated the effect of amyloid pathology on the
development of apathy.

"Combined with earlier studies, our findings strengthen the proposed
idea that cognitive deficits and neuropsychiatric symptoms can develop independently, yet in parallel to one another. They have a common
underlying neuropathology, but to some extent they can also reinforce
one another," said Professor Hansson.

"These findings could ultimately lead to more efficient study design of clinical trials for AD in that they point to neuropsychiatric symptoms
as potential alternative outcome measures," concluded Professor Hansson.

John Krystal, MD, Editor of Biological Psychiatry, said of the new
findings, "We are used to thinking about Alzheimer's disease from the perspective of memory impairments. This new study highlights that the
earliest signs of amyloid-related pathology may be changes in mood and behavior, particularly apathy and anxiety."

========================================================================== Story Source: Materials provided by Elsevier. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Maurits Johansson, Erik Stomrud, Per Maarten Johansson, Anna
Svenningsson, Sebastian Palmqvist, Shorena Janelidze, Danielle
van Westen, Niklas Mattsson-Carlgren, Oskar Hansson. Development
of apathy, anxiety, and depression in cognitively unimpaired
older adults: effects of Alzheimer's disease pathology
and cognitive decline. Biological Psychiatry, 2022; DOI:
10.1016/j.biopsych.2022.01.012 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220316100426.htm

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