By Khalid Iqbal (Editor), Sangram S. Sisodia (Editor), Bengt Winblad (Editor)
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Additional resources for Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics
1999). However, it may still be the case that some tasks are more effective than others in predicting future development of AD. Ba¨ckman and Small (1998) examined the effect of cognitive support on the results of memory tasks in preclinical AD. Four different tasks that varied systematically with regard to the degree of cognitive support (more study time, organizability, and semantic retrieval cues) were administered. As expected, the incident AD cases showed a clear performance deﬁcit at baseline (three years before diagnosis) but the same qualitative pattern as the controls, with performance gradually increasing across increasing levels of cognitive support.
DIAGNOSING VERY MILD CASES OF DEMENTIA IN EPIDEMIOLOGICAL STUDIES Most of the prevalence studies cited have used either Mini-Mental State Examination (MMSE) scores of 24 or lower or equivalent scores on related tests as a screening tool. , 1989). 1). Today we often diagnose clinical AD and dementia in less impaired individuals with a fair degree of accuracy. Can this be done in the briefer evaluations required for epidemiological studies? Inclusion of cases of dementia at a very early stage in the course of the illness is now recognized as important, but raises the issue of the accuracy of diagnoses in very mild dementia and also the issue of the accuracy of the differential diagnosis in dementia in the setting of an epidemiological study, where autopsy follow-up is unlikely.
Dr Frangione demonstrated in 1990 that in Dutch patients, the gene coding for the amyloid precursor protein (APP) contained a point mutation. This work provided an enormous stimulus to look for mutations in other amyloidosis and established a rationale for examination of mutations of the APP gene in pedigrees of FAD. Dr Frangione proposed that a conformation change occurs in sA due to point mutations and/or a post-translational modiﬁcation leading to aggregation and ﬁbrillation. This conformational/aggregational transformation could also result from changes in pH, local concentration, lack of clearance and interaction with other molecules, which he terms ‘pathological chaperones’, and he identiﬁed apolipoprotein E (apoE) as one of these long before linkage analysis demonstrated an association between apoE and late onset FAD and sporadic AD.