The Natural History of Alzheimer Disease: A Longitudinal Presymptomatic and Symptomatic Study of a Familial Cohort

• Published in: Archives of neurology (Chicago) Vol. 61; no. 11; pp. 1743 - 1748
• Main Authors: Godbolt, Alison K, Cipolotti, Lisa, Watt, Hilary, Fox, Nick C, Janssen, John C, Rossor, Martin N
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.11.2004
• Subjects: Adult; Age of Onset; Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Biological and medical sciences; Cognition Disorders - etiology; Cognition Disorders - physiopathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Longitudinal Studies; Male; Medical sciences; Mental Status Schedule; Middle Aged; Nervous system (semeiology, syndromes); Neurologic Examination; Neurology; Nervous system diseases; Degenerative disease; Alzheimer disease; Cohort study; Central nervous system disease; Cerebral disorder
• ISSN: 0003-9942; 2168-6149; 1538-3687; 2168-6157
• DOI: 10.1001/archneur.61.11.1743

BACKGROUND Knowledge of the evolution of cognitive deficits in Alzheimer disease is important for our understanding of disease progression. Previous reports, however, have either lacked detail or have not covered the presymptomatic stages. OBJECTIVE To delineate the onset and progression of clinical and neuropsychological abnormalities in familial Alzheimer disease. METHODS Nineteen subjects with familial Alzheimer disease underwent serial clinical and neuropsychological assessments. Eight of these had undergone presymptomatic assessments. The follow-up period was 1 to 10 years (mean, 5 years). The relative timing of the occurrence of 3 markers of disease onset and progression (onset of symptoms, Mini-Mental State Examination score ≤ 24, and impaired scores on a range of neuropsychological tests) were compared using the binomial exact test. RESULTS Neurological abnormalities were not prominent, although myoclonus appeared early in some. Mini-Mental State Examination score was not sensitive to early disease. Memory and general intelligence deficits appeared at an earlier stage, in some patients when presymptomatic. Perceptual, naming, and especially spelling skills were preserved to a late stage. CONCLUSION Familial Alzheimer disease may have a long prodromal phase of several years with subtle deficits initially of general intelligence and memory, while spelling, naming, and perception are relatively preserved until a late stage.Arch Neurol. 2004;61:1743-1748-->