ABSTRACT
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with characteristic clinical and pathological features. Alzheimer’s disease is aetiologically heterogeneous and can be produced by mutations of chromosomes 21, 14 and 1 as well as by as yet unrecognized causative factors. Clinical variations are common including differences in age at onset, rate of progression, pattern of neuropsychological deficits, and occurrence of non-cognitive neuropsychiatric symptoms.1 Except in rare cases of identifiable mutations in presymptomatic individuals, there are currently no biological markers available for AD that allow preclinical detection or definitive premorbid diagnosis. Pathologically, characteristic findings include neuronal loss, neurofibrillary tangles, neuritic plaques and amyloid angiopathy; the severity of each of these changes differs considerably among individual patients. Thus, AD exhibits aetiological, clinical and pathological heterogeneity. This diversity makes accurate diagnosis more difficult. Correct diagnosis is critical to advancing research in AD, implementing treatment of AD and identifying non-AD causes of dementia. This introductory chapter reviews current clinical definitions of AD, discusses strengths and weaknesses of the three major definitional approaches, describes disorders with features that overlap with those of AD and makes recommendations for improving diagnostic precision.
