In a biracial urban population, we characterized change in depressive symptoms in older persons as they developed AD and the disease progressed. There was a barely perceptible increase in symptoms before the diagnosis and even less change after it, with comparable results in African American and white subjects. The findings suggest that AD has little systematic effect on depressive symptoms.
Knowledge about depressive symptoms in AD comes mainly from cross-sectional studies. Thus, in defined populations, persons with MCI, dementia, or AD have generally been found to have more depressive symptoms than persons without cognitive impairment,10,11
but these data provide limited insight into the basis of the association between depression and dementia. We are aware of only 2 previous studies that tracked depressive symptoms during the development of AD. One study of older Catholic clergy found no change in self-report of depressive symptoms (10-item, binary response CES-D) during a mean of 3.9 years before the incidence of AD and 3.2 years before the incidence of MCI.12
The other study, like the present one, took place in a defined population and found an increase in self-report of depressive symptoms prior to dementia onset.13
During up to 14 years of observation, there was a mean increase of about 3 points on the original 20-item version of the CES-D, which has 4 response options (scored 0–3) and a 0–60 score range. This represents an increase of about 0.21 unit per year, which is 0.4% of the scale range. By comparison, the average annual increase before AD was diagnosed in the present study was 0.04 unit, which is also 0.4% of the scale range. Taken together, therefore, these 3 studies are in substantial agreement in suggesting that very little change in depressive symptoms occurs prior to dementia onset in AD.
There has been little longitudinal research on depressive symptoms following dementia incidence in AD. In the Religious Orders Study, there was no increase in self-report of depressive symptoms during a mean of 2.8 years of observation after AD incidence.12
The present results replicate and extend those findings by showing virtually no change in depressive symptoms following dementia onset by informant report or self-report in either African American or white subjects.
These data beg the question of why an illness as devastating as AD has so little impact on depressive symptoms. That depressive symptoms do not appear to systematically increase in old age28,29
indicates that chronic illness does not invariably depress mood. In addition, as AD develops, poor memory and impaired executive control are likely to disrupt the continuity of mood states and their ability to regulate behavior. That is, incipient AD may disrupt depressive behavior in somewhat the same way that it disrupts more adaptive functions. Consistent with this idea, longitudinal studies of patients with AD identified in medical settings and followed longer than the present study suggest that depressive symptoms may eventually decrease in the disease.30,31
The relation of depression to the pathologic features of AD has been difficult to establish. In a small study of persons without dementia, depression was associated with elevated cortical uptake of Pittsburgh Compound B, suggesting elevated β-amyloid.32
In persons with AD, a history of depression has been associated with relatively higher levels of AD pathologic lesions.33,34
However, in 2 large clinical–pathologic studies of persons with and without dementia, level of depressive symptoms in the last years of life was not related to the pathologic hallmarks of AD or other common dementias.35,36
Thus, although AD37
and cerebrovascular disease38
may contribute to late-life depression, current data suggest that at least some of the association between depressive symptoms and subsequent cognitive dysfunction1-9
reflects factors other than the pathologic lesions traditionally linked with late-life dementia. Consistent with this idea, depressive symptoms have been associated with reduced density of dendrites and spines in the CA3 region of the hippocampus,39
a characteristic finding in animal models of chronic stress.40
Understanding the neurobiologic pathways linking depressive symptoms to cognitive impairment could suggest novel strategies for delaying symptom onset in dementia.
This study has several strengths. Participants were sampled from a defined population, making it likely that a broad spectrum of incident disease was represented and that the findings are generalizable. Diagnoses of MCI, dementia, and AD were based on a uniform clinical evaluation and widely used criteria applied by an experienced physician, reducing the likelihood of diagnostic error. The availability of psychometrically established measures of depressive symptoms by both self and informant report plus the high rate of follow-up participation enhanced our ability to identify even subtle nonlinear changes in depression. An important limitation is that dementia severity in the subjects with incident AD was mostly mild to moderate so that these results do not rule out change in depressive symptoms during the end stages of the disease.