Early diagnosis of cognitive impairment in the elderly with the focus on Alzheimer's disease.

In dementia disorders, it can be assumed that the pathological process in the brain has been present for a long time. It is therefore of importance to have a preclinical or an early clinical diagnosis. Obviously, vulnerability genes, such as ApoE-4, can be diagnosed preclinically. As we have no treatment to offer patients with genetic risk factors, genotyping for ApoE-4 is at present of no clinical use. Trained neuropsychologists have today access to sensitive tests which reveal cognitive impairment before the disturbances reach the level of dementia. Laboratory investigations of cerebrospinal fluid have so far yielded no great results. Tau protein appears to be the most sensitive marker, but it is unspecific. Chromogranin A separates early onset from late onset Alzheimer's disease and seems to be a marker for synaptic degeneration. Synaptotagmin was also found to be reduced in patients with early onset Alzheimer's disease. Still we do not know, however, whether these proteins are early markers for degenerative processes in the brain. Laboratory investigations of blood have not yielded markers of use in early or differential diagnosis of dementia disorders. In a study at our own institute, however, we found serum-homocysteine (S-HCY) to be an early and sensitive marker for cognitive impairment. In patients with dysmentia (mild cognitive impairment), no less than 39% had pathological S-HCY levels, indicating insufficient 1-carbon metabolism.