A new direction for Alzheimer's research

Abstract

Despite decades of research, at present there is no curative therapy for Alzheimer's disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. The first change is that Alzheimer's disease must be considered a disease of four major pathological processes, not one. The four processes are: 1) vascular hypoperfusion of the brain with associated mitochondrial dysfunction, 2) destructive protein inclusions, 3) uncontrolled oxidative stress, and 4) proinflammatory immune processes secondary to microglial and astrocytic dysfunction in the brain. The second change recommended is to alter the standard cognitive measurement tools used to quantify mental decline in test patients. Specifically the Dementia Severity Rating Scale (DSRS) should supersede Mini-Mental State Examination (MMSE) and other popular tests, and a measurement scale developed in research should be used to produce a linear and non-irregular baseline. Finally, accepting the concept that four etiologies cause Alzheimer's disease leads to the last necessary change, that new therapies must be employed directed against all four causes, likely as a combination. There are drugs ready to be employed in such a combinations which are available and used clinically for other purposes so can be used "off label" and one such combination is suggested.

Keywords: Alzheimer's disease etiologies; Dementia Severity Rating Scale; cognitive testing; combination therapy; failed research; off-label use.

Figure 1

Multiple causes and combintion therapy for Alzhemer's disease.