Alzheimer disease: are we intervening too late? Pro.

The affirmative position is argued in response to the question of whether intervention in the disease course of Alzheimer disease (AD) occurs too late. AD is not a singular, homogeneous disease, but rather a final common pathway or end-point that can be arrived at through multiple routes. As part of the affirmative argument, there is a delineation of two long-term trajectories leading to AD: (1) normal elderly progression to AD, and (2) depressed elderly progression to AD. In documenting normal elderly devolution into AD, two "normal" elderly pre-AD or prodromal stages are discussed: age-associated memory impairment (AAMI) and mild cognitive impairment (MCI). Data are provided evidencing significantly high conversion rates from these pre-AD stages to actual AD. Using the same paradigmatic approach that is used in documenting normal elderly decline into AAMI and MCI with eventual conversion to AD; there is explication of depressed elderly conversion to AD. The long-term, multiphasic disease progression of major depression without dementia to depressive dementia to final conversion to AD is brought into focus as another example of why intervention must occur prior to actual conversion to AD. Depression is defined as a cognitive syndrome and risk factor for AD requiring aggressive targeted intervention. AD does not just come suddenly out of nowhere. First intervention must occur during the pre-AD phases in an attempt to prevent, delay, and interrupt long-term neurodegenerative processes involved in both normal elderly and depressed elderly conversion to AD. A primary strategy proposed is to delay onset of AD. Population statistics indicate that if AD is delayed by a modest 1 year, there would be 9.5 million fewer cases by 2050, resulting in significant reduction in burden of disease. Data show early intervention with cognitive stimulation (mental exercise), physical exercise, aggressive treatment of AD risk factors and excess disability, psychotherapy, and other nonpharmacological interventions in combination with each other and/or with medications can result in delay of onset of AD. First intervention at time of diagnosis of AD is too late, when by definition, final conversion to AD has already occurred. When we have knowledge to successfully intervene earlier, why would we not want to do so.