When Alzheimer's Disease Could Be Diagnosed Only After Death
In 1988, Alzheimer's disease (AD) was a disease defined only by its progressive dementia and characteristic post-mortem brain biopsy pattern of tangled neurological fibers (now called Tau tangles) and accumulation of protein clumps (now called amyloid plaques). 82 years after this debilitating disease was first described by Dr. Alois Alzheimer in 1906, ".... clinical diagnosis was uncertain, you could only diagnose it reliably with histopathology, no genes were known to be associated with it and the prevalent view was that nothing can be done about it and anyway, it is an inevitable part of ageing." So said Professor David Smith, Professor Emeritus of Pharmacology at the University of Oxford in a recent address to a global audience of vitamin B12 scientist members of CluB-12 UK, a non-profit organization recently formed to foster scientific cooperation to advance recognition, diagnosis and management of B12 related medical conditions.
The part of the brain that is important for memory and cognitive function is also the part that demonstrates the most extensive pathological change in AD, and Professor Smith and his colleagues set out to see whether the new technology of CT scanning (about 10 years old at that time) could pick up these changes while the patient was still alive. What they discovered when they started looking at CT scans, was that this part of the brain was not captured on the scan. The radiologist explained that the angle of radial imaging of the CT device was purposely set to image most of the brain, but not all of it, for fear of giving excess radiation to the orbit. The part that it missed completely was the the hippocampus in the medial temporal lobe - the precise location of degeneration in AD.
The scientists persuaded their radiology colleagues to add an approach to include this part of the brain (behind the orbit) and they developed a protocol to measure the thickness of the medial temporal lobe (MTL) and struck gold. Scanning patients (with AD and dementia) and control subjects (without) for one or more years before death confirmed that an MTL below a threshold thickness diagnosed AD in 80% of patients (confirmed by post-mortem histology). The false positive rate was 1%. This was a huge break-through. Being able to identify changes that correlate so highly with this disease during life and non-invasively was critical in being able to explore ways to prevent or mitigate its impact.