New developments in the diagnosis of dementia

Abstract

Background: The terms "dementia" and "Alzheimer's disease" are often wrongly used as if they were synonyms. Dementia is a clinical syndrome whose main element is memory impairment; it is due to Alzheimer's disease in more than 75% of cases. Alzheimer's disease, on the other hand, is a neuropathological entity that is characterized by a protracted preclinical phase followed by the onset of slowly progressive dementia.

Methods: We here review relevant literature that we retrieved by a selective Medline search (2005-2009), paying special attention to the early diagnosis of Alzheimer's disease, its clinical manifestations, and its relevance in primary care.

Results: The early clinical manifestations of a dementing illness can be detected in primary care through the use of simple screening tests such as the mini mental state examination, clock drawing tests, and DemTect. A diminished concentration of Abeta-peptide and an increase of (phospho-)tau in the cerebrospinal fluid can suggest the presence of Alzheimer's disease even before the onset of dementia: these substances are components of amyloid plaques and neurofibrillary tangles, which are the characteristic neuropathological lesions of Alzheimer's disease. New types of morphological magnetic resonsance imaging (MRI), and automated analysis of the images obtained, can improve the consistency of radiological assessment over the traditional visual method and thus enable more secure diagnosis.

Conclusion: The early, preclinical phase of Alzheimer's disease involves what has been termed mild cognitive impairment and may last as long as five years until the onset of dementia. With the aid of the new biomarkers described here, the likelihood of diagnosing Alzheimer's disease correctly in this phase can be raised above 80%. Early detection of Alzheimer's disease before the onset of dementia provides an opportunity to study potential approaches for secondary prevention, which are now an object of intense clinical research.

Figure 1

The typical progressive course of Alzheimer’s disease, starting with a preclinical phase lasting several years before overt dementia develops. Patients in the preclinical phase often have (amnestic) MCI combined with hyposmia and/or a depressive mood disturbance. Impairment of activities of daily living appears at dementia onset; later on, further cognitive disturbances arise, such as aphasia, agnosia, apraxia, and/or impaired executive function. MCI = mild cognitive impairment

Figure 2

Typical clock drawings by patients with early Alzheimer’s dementia. The patients were asked to draw the face of a clock showing ten minutes past eleven o’clock within a pre-drawn circle. The minute hand can no longer be correctly placed (15); reproduced with the kind permission of the publisher, SAGE

Figure 3

Morphological MRI scans subjected to automated image analysis. Color coding is used to indicate the brain areas that are particularly informative for the computer program with regard to the differential diagnosis of Alzheimer’s disease from normal aging. The blue and green areas are mainly in the hippocampus and are reduced in size in the patients with Alzheimer’s disease; modified from Reference 20, Diagram 2; reproduction rights belong to the author, S. Klöppel