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Cognitive dysfunction, hippocampal atrophy and glucocorticoid feedback in Alzheimer's disease.
Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Geriatric Medicine.
Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Geriatric Medicine.
Umeå University, Faculty of Medicine, Radiation Sciences.
Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Geriatric Medicine.
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2006 (English)In: Biological Psychiatry, ISSN 0006-3223, Vol. 59, no 2, 155-161 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2006. Vol. 59, no 2, 155-161 p.
Keyword [en]
Aged, Aged; 80 and over, Alzheimer Disease/blood/*complications/pathology, Atrophy, Cross-Sectional Studies, Cushing Syndrome/blood/*complications/diagnosis, Dexamethasone/diagnostic use, Feedback; Biochemical, Female, Hippocampus/*pathology, Humans, Hydrocortisone/*blood, Hypothalamo-Hypophyseal System/physiopathology, Limbic System/physiopathology, Magnetic Resonance Imaging, Male, Memory Disorders/blood/*complications/diagnosis, Middle Aged, Neuropsychological Tests, Organ Size, Pituitary-Adrenal System/physiopathology, Principal Component Analysis, Severity of Illness Index
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-15322DOI: 10.1016/j.biopsych.2005.06.017PubMedID: 16125145OAI: diva2:154994
Available from: 2008-01-16 Created: 2008-01-16 Last updated: 2010-03-19Bibliographically approved
In thesis
1. Neuropsychological Function in Relation to Structural and Functional Brain Changes in Alzheimer’s Disease
Open this publication in new window or tab >>Neuropsychological Function in Relation to Structural and Functional Brain Changes in Alzheimer’s Disease
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this doctoral thesis was to study neuropsychological function in relation to structural and functional brain changes in Alzheimer´s disease (AD).

In the first study relations between hippocampal volume, neuropsychological function and limbic-hypothalamic-pituitary-adrenal (LHPA) axis disturbances in AD were investigated with magnetic resonance imaging (MRI). Reduced hippocampal CA1 volume and suppressed cortisol levels in combination, best predicted the variation in neuropsychological performance. The conclusion was that reduced hippocampal volume and LHPA axis disturbances are associated to level of cognitive function in AD.

The second study focused on whether patients with early AD showed an altered regional cerebral blood flow (rCBF) pattern compared to control persons, correlation between performance on memory tests and rCBF in sub-lobar volumes of the brain were investigated. The rCBF was measured with single photon emission computed tomography (SPECT). AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus compared to controls. The diagnostic sensitivity and specificity for AD was high in temporoparietal regions. AD-patients had significantly lower performance on semantic and, in particular, episodic memory-tests compared to the controls, and their performance on several episodic tests correlated with rCBF in parietal and temporal regions including left hippocampus, which suggest that abnormalities in the rCBF pattern underlie impaired episodic memory functioning in AD. The conclusion was that an observer-independent analyzing method for SPECT with sub-lobar volumes VOI´s is promising in the diagnosis of AD.

In a third study possible differences in memory-related functional brain activation between persons with high versus low risk for AD were examined with functional magnetic resonance imaging (fMRI). The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences. During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal and hippocampal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. The conclusion was that patterns of prefrontal brain activity related to episodic memory differed between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease.

In a final study SPECT was used to map patterns of rCBF in an activated state (an episodic encoding task) and in a rest condition in persons with mild AD and in healthy elderly control persons. A reduction of rCBF in temporoparietal regions that was more pronounced in mild AD in the activated encoding task was observed. The conclusion was that there are rCBF differences between mild AD patients and healthy controls in temporoparietal regions, and the temporoparietal reduction is more pronounced during activation than during rest which might be important in the early diagnosis of AD.

Taken together, these findings show that level of neuropsychological function, notably episodic memory, can be systematically related to functional disturbances in the LHPA axis and to the function of temporoparietal and prefrontal brain regions in AD patients. These changes are detectable in patients with risk for AD and in an early phase of AD which suggests that the obtained results might be important for early diagnosis of AD.

78 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 903
Alzheimer´s disease, neuropsychological function, episodic memory, hippocampus, prefrontal cortex, brain imaging, MRI, fMRI, SPECT, LHPA-axis, cortisol
Research subject
urn:nbn:se:umu:diva-323 (URN)91-7305-691-X (ISBN)
Public defence
2004-10-22, Betula, 6M, 09:00 (English)
Available from: 2004-09-29 Created: 2004-09-29 Last updated: 2010-03-19Bibliographically approved

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