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Reductions in hippocampal volume occurring with late-life depression have no association with levels of amyloid deposition, indicating that hippocampal volume reduction may not necessarily be relied upon as a sign of the onset of Alzheimer's disease, according to new research.

"Lower hippocampal volume was not related to amyloid pathology in this sample of patients with late-life depression," the authors write.

"These data counter the common belief that changes in hippocampal volume in late-life depression are due to prodromal Alzheimer's disease," they add.

The findings come from a study published online August 19 in the American Journal of Psychiatry..

These findings have important clinical implications, because hippocampal volume is a measure that is routinely used in the diagnostic workup of patients with Alzheimer's disease, senior author Mathieu Vandenbulcke, MD, PhD, of the Department of Old Age Psychiatry, Universitair Psychiatrisch Centrum KU Leuven, Belgium, told Medscape Medical News.

"The clinical message from this is that doctors should be careful in interpreting mild changes in hippocampal volume when they suspect Alzheimer's disease in patients with a late-life depression," he said.

Changes Seen in Depressed Patients' Brains

The study was conducted in 100 patients older than 60 years who were recruited from the Department of Old Age Psychiatry of the University Psychiatric Center, in Leuven, Belgium. Of the particiapnts, 48 were currently depressed older adults, and 52 were healthy age- and sex-matched control persons.

Assessments with structural MRI, [18F]flutemetamol amyloid positron-emission tomography, apolipoprotein E genotyping, and neurophysical assessment showed there were significant differences in mean normalized total hippocampal volume between persons who were and who were not depressed (P = .02).

There were no differences between the two groups with regard to cortical amyloid uptake or proportion of amyloid-positive patients. Amyloid deposition is considered a hallmark of Alzheimer's disease.

After excluding persons who were positive for amyloid deposition, those with depression still showed greater reductions in hippocampal volume. Furthermore, no association was seen between hippocampal volume and amyloid uptake in either group.

Several Theories to Explain the Findings

It is well documented that reductions in hippocampal volume occur with late-life depression. Such reductions are often suspected of having a link to Alzheimer's disease, because the disease is characterized by hippocampal atrophy and because Alzheimer's disease is often preceded by late-life depression.

In the absence of amyloid pathology, alternative theories for the hippocampal volume loss with late-life depression include a suspected nonamyloid pathology. This could explain a known link between the volume loss and the increased risk for dementia with late-life depression, the authors explain.

It is also believed that vascular impairment may play a role in nonamyloid brain changes. The new study found no association between white matter hyperintensity and hippocampal volume.

Another theory is the stress hypothesis, according to which loss of hippocampal volume could result from stress-related mechanisms such as toxicity from elevations in the level of cortisol. This theory is supported by some studies linking longer duration of depression with smaller hippocampal volume.

Dr Vandenbulcke noted, however, that the new study found no evidence of a significant decrease in hippocampal volume in a subset of patients with early-onset depression (onset before the age 55 years, 42%) compared with late-onset depression.

Yet another theory for the hippocampal reduction in late-life depression is the "vulnerability hypothesis," according to which preexisting lower hippocampal volume may itself be a cause of sensitivity to depression and stress, rather than an effect.

"As the hippocampus is involved in stress and emotion regulation, it is possible that a lower hippocampal volume predisposes to depression," Dr Vandenbulcke explained.

"Moreover, normal aging is also associated with mild hippocampal volume changes. These effects may be additive, leading to increased risk for depression later in life, next to age-related psychosocial stressors," he said.

Story Source: The above story is based on materials provided by MEDSCAPE