Researchers here claim that the high degree of overlap between Alzheimer's disease and vascular dementia could account for the difficulty in translating promising research results into successful clinical trials for Alzheimer's therapies. If patient cognitive decline is largely due to the vascular dementia in a sizable proportion of cases, that would be enough to tip the trial into failure when the benefits for Alzheimer's symptoms were modest. If large benefits could be produced, however, if the pathology of Alzheimer's could be cleared away, then it would be clear as to whether the therapy worked even if only half the patients saw a meaningful reduction in symptoms. Much of the difficulty in modern medicine exists precisely because most therapies for age-related disease are only producing small benefits, and thus trials results can be prone to misinterpretation due to any number of confounding factors.
Because Alzheimer's disease (AD) is the leading cause of dementia, many people use the two terms interchangeably. But inadequate blood flow to the brain due to microinfarcts, mini-strokes, or strokes is a hallmark of a disease called Vascular Cognitive Impairment and Dementia (VCID). VCID is the second most common cause of dementia, and the two are not mutually exclusive - researchers estimate that 40-60% of Alzheimer's disease patients also have VCID. A paper recently published reports that a certain form of immunotherapy targeted to Alzheimer's patients may be ineffective when that patient also has VCID. "These findings are important in that they provide a possible explanation for why clinical trials of anti-Aβ immunotherapy for Alzheimer's disease have been historically unsuccessful. If up to 40 percent of people with Alzheimer's also have VCID, treatment candidates that target only the AD physiology won't be effective in those patients. It's like treating only half the disease."
Most researchers agree that the formation of brain plaques containing amyloid β (Aβ) peptides is an initial step in the development of Alzheimer's disease, which has led to a race to identify and test treatments that reduce the levels of these plaques. Anti-Aβ immunotherapy, which uses antibodies against Aβ to clear it from the brain, has been a leading approach. While these drugs showed promise in animal studies, clinical trials have failed to show similar benefits in human patients. Without a suitable animal model, testing the vascular dementia hypothesis would not have been possible. Fortunately, the research team had already developed an innovative model of combined AD and VCID. Using this mouse model, together with its parent model of AD without VCID, scientists evaluated the ability of an anti-Aβ antibody to enhance cognitive capabilities in both models. While Aβ levels were reduced in both groups, cognitive function was not improved in the groups with combined AD and VCID. "The failure of anti-Aβ immunotherapy in the mixed AD-VCID model suggests that both disease processes have to be treated to have a successful outcome. The missing link has been that our animal models usually possess the hallmarks of only one disease, which has led to failure of successful translation to clinic."