Alzheimer disease: are we intervening too late?

Abstract

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.

A study on the specificity of the association between hippocampal volume and delayed primacy performance in cognitively intact elderly individuals

“…Nonetheless, early, pre-clinical, intervention has been proposed as a viable solution to delay the onset of the disease and reduce prevalence (Emery, 2011; but see Ames, 2011). The identification of subjects at elevated risk of conversion to AD has benefited a great deal from research into the genetic correlates of AD (e.g., the APOE ε4 allele; Blennow, DeLeon & Zetterberg, 2006; Corder et al, 1993).…”

Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer's disease

“…Drugs currently licensed for use temporarily slow disease progression in some affected individuals but there is no evidence that they delay or prevent onset of AD [4,42,51]. The reduction of oxidative stress has been a therapy target in clinical trials, but results have largely been negative, or mild at best [9,52,53] (See other sources for approaches currently being considered in AD [4,9,54–60]. ).…”

Central Nervous System Drug Consumption Depending on the Time between Symptom Onset and the Diagnosis of Alzheimer’s Disease: An Analysis by the Registry of Dementias of Girona

“…The insidious onset of AD, and its increasing prevalence and economic burden, has brought into focus the need for an early detection to delay cognitive decline and other AD-related symptoms [9]. According to our results, only 10% of the cases were diagnosed in less than 1 year after the first symptoms, around 55% were diagnosed in less than 3 years, and it took longer than 3 years to diagnose the rest.…”

“…Also, an early and accurate diagnosis allows the detection of treatable disorders that may increase cognitive impairment [8]. Although to date there is no cure for AD, an early detection is crucial to delay the neurodegenerative process [9], and the time elapsed between the first symptoms and the diagnosis of dementia should be as short as possible in order to initiate both medication and cognitive stimulation.…”