Cognitive dysfunction, hippocampal atrophy and glucocorticoid feedback in Alzheimer's disease.
BACKGROUND
The hippocampal formation is damaged early in Alzheimer's disease (AD). An association between temporal lobe volume and cognitive function has been shown in several studies. Increased limbic-hypothalamic-pituitary-adrenal (LHPA) axis function has been suggested to be related to hippocampal atrophy and cognitive impairment. Our hypothesis was that there is a clear link between hippocampal volume -- notably of the CA1 region -- memory (episodic and visuospatial) and decreased feedback sensitivity in the LHPA axis in AD.


METHODS
Sixteen medication-free outpatients with mild to moderate AD were included. Hippocampal volume was measured with magnetic resonance imaging. Dexamethasone suppression tests were performed using .5 mg and .25 mg dexamethasone. Three different components in the neuropsychological battery -- Rey 15 item memory test, Alzheimer's Disease Assessment Scale (ADAS) word recall and spatial span from Wechsler Adult Intelligence Scale - Revised neuropsychological instrument (WAIS-R NI) -- were found to represent episodic and visuospatial memory.


RESULTS
Low hippocampal CA1 volume and high post-dexamethasone cortisol levels in combination were significantly associated with Rey 15 item memory and spatial span test outcomes. No association was found between LHPA feedback and hippocampal volume.


CONCLUSIONS
Low hippocampal volume and a disturbed negative feedback in the LHPA axis link to specific cognitive impairments in Alzheimer's disease.
Elgh
Eva
E
Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, SE-901 87 Umeå, Sweden. eva.elgh@germed.umu.se
Lindqvist Astot
Ann
A
Fagerlund
Markku
M
Eriksson
Sture
S
Olsson
Tommy
T
Näsman
Birgitta
B
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000150:complications* / Q000473:pathology; D001284:Atrophy; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D003907:Dexamethasone; D025461:Feedback, Physiological; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008032:Limbic System / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D025341:Principal Component Analysis; D012720:Severity of Illness Index
D003907:Dexamethasone; D006854:Hydrocortisone