Inflammatory signaling in Alzheimer disease and depression
ABSTRACT
To help define the relationships among inflammation, Alzheimer disease, and depression, the Texas Alzheimer’s Research Consortium analyzed an array of inflammatory biomarkers in a cohort of patients with Alzheimer disease and in controls. Inflammation severity was highly correlated with earlier age at onset of Alzheimer disease and was also associated with cognitive decline. The relationship between inflammation and depression was not as clear, and it varied with aspects of depression, gender, and the presence of Alzheimer disease.
Inflammation is associated with Alzheimer disease
Degree of inflammation also correlated with Mini-Mental State Examination (MMSE) scores. Subjects with a high inflammatory score had a more accelerated decline in MMSE scores over a 3-year period than those with a low inflammatory score. The association was significant, although not as dramatic as the association between inflammation and age at onset of Alzheimer disease.
The investigators concluded that their findings, while considered preliminary, suggest the existence of an inflammatory endophenotype associated with Alzheimer disease. The findings need to be validated in other populations, including ethnic groups other than Caucasian. The Consortium also will evaluate whether inflammatory biomarkers are associated with progression of mild cognitive impairment to Alzheimer disease.
Inflammation has a mixed association with depression
In a study whose results are not yet published, the Texas Consortium also examined the association between inflammatory markers and depression. Four subscales of depression were used, derived from the Geriatric Depression Scale (GDS) 30: dysphoria (consisting of 11 items), meaninglessness (seven items), apathy and withdrawal (six items), and cognitive impairment (six items).5
The GDS30 results as a whole suggested a trend toward an association between depression and inflammatory biomarkers, but the association was not significant. When the results were examined by subscale, however, striking differences were found between Alzheimer patients and the control group. For example, apathy was significantly associated with the C-reactive protein level, and the assocation was much stronger in patients with Alzheimer disease than in controls. Further, the association of apathy with C-reactive protein level was more significant in women than in men.
Other associations were found between several of the inflammatory and antiinflammatory cytokines and the various subscales; the relationship between inflammatory factors and depression appears to be complex and often gender-specific.
Inflammation-depression link is suggestive, not linear
Despite the relationships suggested by the data, no simple linear relationship was identified to indicate that more inflammation leads to more depression in Alzheimer disease. The relationship between inflammation and depression in Alzheimer disease appears to involve a complex interplay between many physiologic processes.
The effect of inflammation also varies with gender and with cognitive impairment. The mechanism that underlies these relationships remains to be determined and will be the focus of further studies with the Texas Alzheimer’s Research Consortium.
