Con: Can biomarkers be gold standards in Alzheimer's disease?

The syndrome of dementia is greatly feared by many people, robbing them of their dignity, independence and ability to lead a meaningful life - at least on the terms set by their predementia selves. The diagnosis of dementia can be difficult, especially for nonexperts. First, the syndrome of dementia needs to be distinguished from somewhat less onerous diagnoses, such as deafness, depression and delirium. Next, when the dementia is established, its cause needs to be sought out.In practice, the syndromic diagnosis is more complicated still - even for experts - because it is common to identify people who have verifiable memory symptoms, and sometimes even mild decline in one of two other cognitive domains. What can be especially tricky is that many such people appear not (yet) to have reached a threshold of functional impairment that would allow a dementia diagnosis to be made with confidence. This state of cognitive impairment without important cognitive decline is best known as mild cognitive impairment. Of some interest is the fact that this state places the person so affected at much higher (but not certain) risk for developing unequivocal dementia. For these reasons - diagnostic uncertainty, the need to distinguish, early on, those at greatest risk, and (as discussed below) the need to monitor treatment effects - much effort is now being devoted to developing and validating so-called biomarkers. But how reasonable is it that biomarkers will meet these important challenges?Biomarker is the term given to 'measurable biological characteristics that can either serve as indicators of normal or pathogenic processes in the body, or as tools to track pharmacological responses to therapeutic drugs' [1]. Their validation in dementia is inspiring an enthusiasm that seems imprudent to many people, because it glosses an essential aspect of how to test tests.Validity can be understood in many ways, but a trinitarian approach of content, construct and criterion validity is well