麻豆传媒

Early Alzheimer's pathology was not consistently linked to depressive symptoms in people without clinical dementia, cross-sectional data suggested.

In people with normal cognition, depressive symptoms and amyloid pathology were not associated with each other (OR 1.13, 95% CI 0.90-1.40, P=0.29), reported Julie Oomens, PhD, of Maastricht University in the Netherlands, and co-authors.

However, in people with mild cognitive impairment, the presence of depressive symptoms was tied to a lower likelihood of amyloid pathology (OR 0.73, 95% CI 0.61-0.89, P=0.001), Oomens and colleagues said in .

The findings suggest that other mechanisms may underlie the previously seen associations between depressive symptoms and cognitive decline in late life, Oomens and colleagues observed.

"This large-scale study including data from 49 cohorts included in the Amyloid Biomarker Study shows that depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in persons without dementia," Oomens told 麻豆传媒. "This means that the earlier identified association between depressive symptoms and cognitive decline is likely not explained by Alzheimer's disease pathology."

The research raises an important question about cohort studies with outcomes that, like depression, have heterogeneous symptoms, observed Jennifer Gatchel, MD, PhD, of Massachusetts General Hospital in Boston, who wasn't involved with the study.

"In studies with such large samples, deep phenotyping of clinical samples is not typically practical or feasible, and key information about context is missed," Gatchel told 麻豆传媒.

Depressive symptoms at the time participants were assessed might have represented a long-standing psychiatric disorder, mild behavioral impairment, or a combination of the two. "This distinction is critical, as not all depressive symptoms are created equal," Gatchel pointed out.

Prior work, including research from the Harvard Aging Brain Study by Gatchel and others, was longitudinal, not cross-sectional. "Our sample included cognitively normal older adults without significant depression and with low levels of amyloid at baseline," she explained. "In this context, we found that the rise in depressive symptoms over time was associated with regional amyloid accumulation in this specific group."

In their analysis, Oomens and colleagues evaluated 9,746 individuals with normal cognition and 3,023 people with mild cognitive impairment in the Amyloid Biomarkers Study, an ongoing collection of information from research studies and memory clinics that's been pooling data since 2012. Participants were ages 34 to 100 and had data about amyloid biomarkers and depressive symptoms.

Amyloid pathology was determined by positive cerebrospinal fluid tests or PET scans. The presence of depressive symptoms was assessed by validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms.

Participants with normal cognition had a mean age of 69 years; 34% were APOE4 carriers, 9.6% had depressive symptoms, and 27.2% had amyloid pathology. People with mild cognitive impairment had a mean age of 70 years; 44.8% were APOE4 carriers, 27.3% had depressive symptoms, and 55.8% had amyloid pathology.

In people with normal cognition, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE4 noncarriers, but not in APOE4 carriers. In people with mild cognitive impairment, however, no interaction effect for APOE4 status was seen.

Severity of depressive symptoms was not associated with amyloid pathology in people with normal cognition, but was tied to a lower likelihood of amyloid pathology in those with mild cognitive impairment.

In both people with normal cognition and those with mild cognitive impairment, the relationship between the presence of depressive symptoms and amyloid pathology was dependent on the rating scale used.

"One possible explanation may be that the depression scales included [in the study] measure different aspects of the depressive symptom spectrum and that these may be differentially related to amyloid pathology," Oomens and colleagues said. "Some of the rating scales used may also be more tailored to the specific population included in the study than others."

The overall lack of significant associations in people with normal cognition that emerged in this study must be interpreted in light of the relatively low burden of depressive symptoms (9.6%) in this group, the researchers acknowledged.

The analysis did not include any possible effects of antidepressant use. People with severe depression were most likely excluded from the underlying studies.

"Additionally, it is important to note that an elevated score on depressive symptom questionnaires does not necessarily imply a clinical diagnosis of major depressive disorder, as certain elements of the depressive syndrome (e.g., disturbances of sleep or appetite) may be caused by various medical conditions common in older adults," Oomens and colleagues noted.

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