A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects.
OBJECTIVE
This study determined whether cognitive impairments and structural brain changes in older depressed subjects, especially in the hippocampus, are related to hypercortisolemia.


METHODS
Sixty-one depressed subjects over age 60 who met DSM-IV criteria for major depression and 40 healthy comparison subjects underwent structural magnetic resonance imaging, neuropsychological testing, apolipoprotein E (APOE) genotyping, and salivary cortisol assessment (over 3 days) with follow-up 6 months later. Hippocampal volume was measured by manual segmentation that was blind to diagnosis. Average area under the curve for salivary cortisol over the 3 days was calculated. Cognitive function was assessed by using a combined memory z score.


RESULTS
Depressed subjects showed multiple impairments in attention, working memory, visual memory, verbal memory, new learning, and executive function in relation to comparison subjects. They had hypercortisolemia (53% increase in area under the curve) and a reduction in right hippocampal volume (6% decrease). Hippocampal volume reduction was not associated with increased cortisol levels but was significantly correlated with continuing memory deficits at 6 months. Persisting "mild cognitive impairment" was seen in 20 (41%) of 49 subjects at 6 months and was associated with reduced hippocampal volume but not severity of depression, cortisol levels, or APOE genotype.


CONCLUSIONS
Older depressed subjects have persisting cognitive impairments associated with hippocampal volume reduction, but the results do not support cortisol-mediated hippocampal neurotoxicity as the major etiological mechanism. Neuropathological studies are required to investigate the basis for hippocampal changes, while follow-up will determine whether hippocampal atrophy is a risk factor for cognitive decline.
O'Brien
John T
JT
Wolfson Research Centre, Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle Upon Tyne NE4 6BE, U.K. j.t.obrien@ncl.ac.uk
Lloyd
Adrian
A
McKeith
Ian
I
Gholkar
Anil
A
Ferrier
Nicol
N
D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D002940:Circadian Rhythm / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis*; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000523:psychology; D005260:Female; D015577:Geriatric Assessment; D006624:Hippocampus / Q000033:anatomy & histology*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis* / Q000097:blood; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012463:Saliva / Q000737:chemistry*
D006854:Hydrocortisone