How long does it take to develop Alzheimer’s disease? A study published in the New England Journal of Medicine (July 11, 2012) indicates that a rare and aggressive form of Alzheimer’s disease produces measurable changes 25 years before clinical symptoms appear.

There is a rare form of familial Alzheimer’s disease where carriers of a gene mutation are afflicted with symptoms in their 30s and 40s (20s for some). This early onset (autosomal-dominant) form of Alzheimer’s disease is inherited in a pattern similar to Huntington’s chorea. We inherit pairs of genes (one of two possible from each parent). In early-onset Alzheimer’s disease one gene is normal and the other carries the program for the illness. In carrier families half of the children with develop the disease and half will not.

Fortunately, most cases of Alzheimer’s disease are late-onset – we are more likely to be afflicted by the disease as we age –especially into our 80s and beyond. It has been clear for some time that Alzheimer’s disease develops well before we can detect actual symptoms. Studying cases of early-onset disease allows us to follow those with the faulty gene and better understand the course and timeline for the disease. The hope is that the process is similar for those with late onset disease.

The Dominantly Inherited Alzheimer’s Network, DIAN, study of these high risk individuals completed numerous baseline and clinical/cognitive assessments on those enrolled in their data bank. The following timeline emerged:
1. Concentrations of amyloid and tau proteins were elevated 25 years before the onset of symptoms in carriers.
2. Siblings without the mutant gene had no detected change in these markers.
3. Imaging studies detected amyloid deposition in the brain (using the Pittsburg marker) 15 years before symptoms.
4. Increased concentrations of tau protein and brain atrophy were detected 15 years before symptoms.
5. Memory loss and cerebral hypometabolism were detected 10 years before symptoms.
6. Changes in the Mini-Mental State scores were found 5 years before expected symptom onset.
7. Criteria for dementia were detected on average 3 years after symptom onset.

Clearly, early-onset Alzheimer’s disease unfolds over the course of 2-3 decades. We assume the same or a longer time course would be evident in late-onset Alzheimer’s disease. Furthermore, current medical screening tests pick up the changes too late for proactive interventions as they don’t detect changes until 5 years before serious symptoms appear. In short, current intervention studies fall quit short. Longer intervention studies are carried out over the course of 3-5 years and most studies are of much shorter duration. They don’t inform us of significant outcome for a process that unfolds over decades.

The long build up is good news. We have time to set up interventions. For example, memory decline begins at least a decade before dementia. The focus of interventions must be memory. You must learn skills before you need them. It is the habits, routines, expertise that will serve us as well as family that care about us better. We don’t wait until we are 80 to assess and build our financial assets. The same principle holds for memory. The earlier we get assessed and start out memory plan, the better the quality of our life.