I presented this topic to The Villages Philosophy Club on 14 February 2014 and my Powerpoint slides are available:
The brains of people with AD contain “Plaques” of Amyloid Beta, a protein, and tangles of another protein called tau. By the time a person manifests objectively measurable cognitive impairment, Amyloid-β, (Aß), is strongly positive in the regions of the brain known as the “DEFAULT NETWORK” – which are particularly vulnerable to (Aß) deposition.
Aß can fold into a misshapen form that causes other normal Aß molecules to assume the wrong shape and clump together. Proteins may later break off from the aggregate and seed the beginnings of the same process elsewhere. This biochemical domino effect involves a mechanism called “CORRUPTIVE PROTEIN TEMPLATING”.
As this biochemical domino effect spreads through the brain, this inexorable progression of Aß deposits engulfs most areas of the cerebral cortex (the brains outer layer) progressing to the midbrain finally reaching the lower brainstem and cerebellum in the organ’s deepest reaches.
There are no exact transition points that define when a patient has progressed from the pre-clinical phase to the mild cognitive impairment phase and then to the dementia phase.
Diagnosing dementia involves many factors which include:
o A complete physical
o A complete neurologic examination
o MRI & CT scans of the brain
o Blood & Urine tests
o Thorough discussion of patients medical history & symptoms
All of the above with a qualified neurologist and neuropsychologist
From my personal experience, observing my spouse, I could see signs of cognitive problems that needed to be addressed:
o Problems using the microwave
o Problems using TV remotes
o Problems w/ electronics that have to be programmed
o Difficulty organizing M – F pillbox for AM/PM medications
o Difficulty with driving directions through roundabouts
I obtained from a friend connected with the American Academy of Neurology suggestions for possible Neurologist from various institutions and current publications (April 2013) relevant to Mild Cognitive Impairment (MCI), Alzheimer’s dementia, genetic risk factors for late onset AD, recent genes associated with early onset AD, radioactive biomarkers for PET scans of the brain, and biochemical biomarkers present in cerebrospinal fluid (CSF). I also obtained excellent advice from a former classmate MD (specialty Internal Medicine), with experience diagnosing this disease, and his recommendation: “Seek a well- established neurologist in the field and obtain a blood test for the ApoE gene.
After a 3 - 5 hour initial exam with a neurologist associated with the Brain Institute, and the neurology dept., Shands Hospital, U. FL, Gainesville and psychologists on the staff --- the preliminary diagnosis was possible MCI with orders for a full day of neuropsychological testing, MRI of the brain and follow up in 2 months.
With the preliminary diagnosis of MCI, the review article (April 2013) on MCI was very important. The slides on MCI are self-explanatory regarding it’s clinical characterization and the significant interest in understanding the transition from MCI to AD.
After 8 hours of extensive neuropsychological testing at Shands, the final diagnosis was changed from MCI to early stages of AD, verified by the appearance of hippocampal atrophy, one of the first regions of the brain to suffer damage in AD patients. Blood tests results came back: Genotype *E2/*E4 (*E4 is a strong genetic risk factor for Alzheimer’s).
Recommended treatment: begin memory medication (Aricept) ASAP, returning in 4 months for subsequent evaluation of the effectiveness of the medication.
The blood test results for Genotype APO*E2 / APO*E4, are explained in the AAN Review Article Continuum on New Genes and Insights from old Genes, which explains the significance of APO*E4 as a genetic risk factor for AD, increasing the risk by a factor of 3 to 4 fold.
Subsequent slides explain three other genes strongly associated with “early Onset” Alzheimer’s (prior to age 65 and experiments with APP-Transgenic mice, genetically engineered (with the APP gene) to produce the precursor protein from which the human Aβ fragment is generated and spontaneously develops Aβ brain deposits at a relatively consistent age.
Future Experiments with APP-Transgenic Mice hopefully may yield important clues to solving the problem for early detection and the subsequent prevention of dementia.