Brain Advance Access published online on September 29, 2006
Brain, doi:10.1093/brain/awl266
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1 Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
* To whom correspondence should be addressed. Presenilin 1 (PSEN1) mutations cause autosomal dominant familial Alzheimer's disease (FAD). PSEN1 mutation carriers undergo the course of cognitive deterioration, which is typical for sporadic Alzheimer's disease but disease onset is earlier and disease progression is faster. Here, we sought to detect signs of FAD in presymptomatic carriers of the PSEN1 mutation (C410Y) by use of a neuropsychological examination, functional MRI during learning and memory tasks and MRI volumetry. We examined five non-demented members of a FAD family and 21 non-related controls. Two of the five family members were carrying the mutation; one was 20 years old and the other 45 years old. The age of clinical manifestation of FAD in the family studied here is
Received May 25, 2006
Revised August 25, 2006
Accepted August 29, 2006
Article
Enhanced brain activity may precede the diagnosis of Alzheimer's disease by 30 years
Christian R. A. Mondadori 1, Andreas Buchmann 1, Henrietta Mustovic 1, Conny F. Schmidt 2, Peter Boesiger 2, Roger M. Nitsch 1, Christoph Hock 1, Johannes Streffer 1, and Katharina Henke 3 *
2 Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland
3 Department of Psychology, University of Bern, Bern, Switzerland
Katharina Henke, E-mail: henke{at}psy.unibe.ch
Abstract 
48 years. Neuropsychological assessments suggested subtle problems with episodic memory in the 20-year-old mutation carrier. The middle-aged mutation carrier fulfilled criteria for amnestic mild cognitive impairment. The 20-year-old mutation carrier exhibited increased, while the middle-aged mutation carrier exhibited decreased brain activity compared to controls within memory-related neural networks during episodic learning and retrieval, but not during a working-memory task. The increased memory-related brain activity in the young mutation carrier might reflect a compensatory effort to overcome preclinical neural dysfunction caused by first pathological changes. The activity reductions in the middle-aged mutation carrier might reflect gross neural dysfunction in a more advanced stage of neuropathology. These data suggest that functional neuroimaging along with tasks that challenge specifically those brain areas which are initial targets of Alzheimer's disease pathology may reveal activity alterations on a single-subject level decades before the clinical manifestation of Alzheimer's disease.
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