Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer's disease
Authors
Yen Ying Lim
Paul Maruff
Robert H. Pietrzak
David Ames
Kathyrn A. Ellis
Karra Harrington
Nicola T. Lautenschlager
Cassandra Szoeke
Ralph N. Martins, Edith Cowan UniversityFollow
Colin L. Masters
Victor L. Villemagne
Christopher C. Rowe
Document Type
Journal Article
Publisher
Oxford University Press
Faculty
Faculty of Health, Engineering and Science
School
School of Medical Sciences / Centre of Excellence for Alzheimer's Disease Research and Care
RAS ID
18783
Abstract
High amyloid has been associated with substantial episodic memory decline over 18 and 36 months in healthy older adults and individuals with mild cognitive impairment. However, the nature and magnitude of amyloid-related memory and non-memory change from the preclinical to the clinical stages of Alzheimer's disease has not been evaluated over the same time interval. Healthy older adults (n = 320), individuals with mild cognitive impairment (n = 57) and individuals with Alzheimer's disease (n = 36) enrolled in the AUSn Imaging, Biomarkers and Lifestyle study underwent at least one positron emission tomography neuroimaging scan for amyloid. Cognitive assessments were conducted at baseline, and 18-and 36-month follow-up assessments. Compared with amyloid-negative healthy older adults, amyloid-positive healthy older adults, and amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease showed moderate and equivalent decline in verbal and visual episodic memory over 36 months (d's = 0.47-0.51). Relative to amyloid-negative healthy older adults, amyloid-positive healthy older adults showed no decline in non-memory functions, but amyloid-positive individuals with mild cognitive impairment showed additional moderate decline in language, attention and visuospatial function (d's = 0.47-1.12), and amyloid-positive individuals with Alzheimer's disease showed large decline in all aspects of memory and non-memory function (d's = 0.73-2.28). Amyloid negative individuals with mild cognitive impairment did not show any cognitive decline over 36 months. When non-demented individuals (i.e. healthy older adults and adults with mild cognitive impairment) were further dichotomized, high amyloid-positive non-demented individuals showed a greater rate of decline in episodic memory and language when compared with low amyloid positive non-demented individuals. Memory decline does not plateau with increasing disease severity, and decline in non-memory functions increases in amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease. The combined detection of amyloid positivity and objectively-defined decline in memory are reliable indicators of early Alzheimer's disease, and the detection of decline in non-memory functions in amyloid-positive individuals with mild cognitive impairment may assist in determining the level of disease severity in these individuals. Further, these results suggest that grouping amyloid data into at least two categories of abnormality may be useful in determining the disease risk level in non-demented individuals.
DOI
10.1093/brain/awt286
Access Rights
free_to_read
Comments
Lim Y.Y., Maruff P., Pietrzak R.H., Ames D., Ellis K.A., Harrington K., Lautenschlager N.T., Szoeke C., Martins R.N., Masters C.L., Villemagne V.L., & Rowe C.C. (2014). Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer's disease. Brain, 137(1), 221-231. Available here