Researchers have
long studied the risk factors that increase the chances of developing
Alzheimer's – including neuropsychiatric conditions such as depression. Now, scientists say anxiety
symptoms could be a dynamic marker of the disease's early stages.
A new study suggests an association between elevated
amyloid beta levels and the worsening of anxiety symptoms. The findings support
the hypothesis that neuropsychiatric symptoms could represent the early
manifestation of Alzheimer's disease in older adults.
Alzheimer's disease is a neurodegenerative condition that
causes the decline of cognitive function and the inability to carry out daily
life activities. Past studies have suggested depression and other
neuropsychiatric symptoms may be predictors of AD's progression during its
"preclinical" phase, during which time brain deposits of fibrillar
amyloid and pathological tau accumulate in a patient's brain. This phase can
occur more than a decade before a patient's onset of mild cognitive impairment.
Investigators at Brigham and Women's Hospital examined the association of brain
amyloid beta and longitudinal measures of depression and depressive symptoms in
cognitively normal, older adults. Their findings, published January 2018 by The
American Journal of Psychiatry, suggest that higher levels of amyloid beta may
be associated with increasing symptoms of anxiety in these individuals. These
results support the theory that neuropsychiatric symptoms could be an early
indicator of AD.
"Rather than just looking at depression as a total
score, we looked at specific symptoms such as anxiety. When compared to other
symptoms of depression such as sadness or loss of interest, anxiety symptoms increased
over time in those with higher amyloid beta levels in the brain," said
first author Nancy Donovan, MD, a geriatric psychiatrist at Brigham and Women's
Hospital. "This suggests that anxiety symptoms could be a manifestation of
Alzheimer's disease prior to the onset of cognitive impairment. If further
research substantiates anxiety as an early indicator, it would be important for
not only identifying people early on with the disease, but also, treating it
and potentially slowing or preventing the disease process early on." As
anxiety is common in older people, rising anxiety symptoms may prove to be most
useful as a risk marker in older adults with other genetic, biological or
clinical indicators of high AD risk.
Researchers derived data from the Harvard Aging Brain
Study, an observational study of older adult volunteers aimed at defining
neurobiological and clinical changes in early Alzheimer's disease. The
participants included 270 community dwelling, cognitively normal men and women,
between 62 and 90 years old, with no active psychiatric disorders. Individuals
also underwent baseline imaging scans commonly used in studies of Alzheimer's
disease, and annual assessments with the 30-item Geriatric Depression Scale
(GDS), an assessment used to detect depression in older adults.
The team calculated total GDS scores as well as scores
for three clusters symptoms of depression: apathy-anhedonia, dysphoria, and
anxiety. These scores were looked at over a span of five years.
From their research, the team found that higher brain
amyloid beta burden was associated with increasing anxiety symptoms over time
in cognitively normal older adults. The results suggest that worsening
anxious-depressive symptoms may be an early predictor of elevated amyloid beta
levels -- and, in turn AD -- and provide support for the hypothesis that
emerging neuropsychiatric symptoms represent an early manifestation of
preclinical Alzheimer's disease.
Donovan notes further longitudinal follow-up is needed to
determine whether these escalating depressive symptoms give rise to clinical
depression and dementia stages of Alzheimer's disease over time.
Similar conclusion was achieved by earlier meta-analysis
report, submitted in 2015. B. Gulpers and colleagues, from Maastricht
University Medical Center in the Netherlands, conducted a systematic literature
search up to January 2015 to identify all longitudinal studies on the
association between anxiety and cognition. The authors included both community
studies and studies of patients being evaluated in memory clinics for
conversion to dementia. Twenty studies met inclusion criteria.
The results highlighted very strong association between
anxiety and MCI was driven by higher age, the authors suggested that anxiety
might be a prodromal symptom.
One of the reasons the authors undertook a study of
anxiety is the MCI is an important risk factor for dementia, and anxiety and
depression often present together with MCI. They noted that most research has
focused on depression. “Studies are scarce and vary in methodology, especially
according to the setting and stage of the neurodegenerative process.”
They emphasized that whether or not the association is
causal, “it is important for the clinician to be aware of anxiety as a possible
predictor for dementia, especially when the anxiety emerges at late life.”
Sources and
Additional Information:
