Chapter 2 - Clinical Diagnosis of Alzheimer’s Disease

Abstract

The simplest definition of Alzheimer’s disease (AD) is a persistent and worsening memory loss with postmortem confirmation of the gold standard markers of amyloid plaques and tangles in the brain at autopsy. In 1984, the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) differentiated between the clinical diagnosis of milder forms of the disease, referred to as “possible AD,” and more advanced cases as “probable AD.” The recent guideline by the National Institute on Aging and the Alzheimer’s Association (NIA-AA) working group (2011) describes AD as having a gradual onset with continual deterioration in cognitive ability, progressing through a presymptomatic stage (preclinical AD) to mild cognitive impairment (MCI) to mild AD to severe AD. Although it is hypothesized that the pathophysiologic changes associated with AD start one or more decades before the clinical manifestation of symptoms occurs, no single laboratory test is able to diagnose AD with high sensitivity (>90%) and specificity (>90%). Diagnosis of AD is even less accurate for the early stages of the disease. Though AD has a specific clinical phenotype with pathological changes that can be confirmed in vivo using biomarkers according to the criteria set by International Working Group (IWG) (2014), use of these biomarkers is largely limited to the research setting and supporting to clinical diagnosis. Accurate clinical diagnosis of AD remains challenging because of the extended prodromal stages of AD, overlapping clinical features with other non-AD dementias, and multiple unclear molecular etiologies. In general, clinical diagnosis of AD by specialists is still made by excluding other neurological diseases, requiring a complete assessment that considers all possible causes through a series of clinical, psychometric, and brain scanning tests. This chapter describes the current approaches to the clinical diagnosis of AD, with a proposed comprehensive framework presented at the end of the chapter.