P3-272: Differentiating Preclinical Alzheimer’S Disease From Normal Aging: the Effects of age and Amyloid on Cognitive Decline Over 3.5 Years

2016 ◽  
Vol 12 ◽  
pp. P938-P938 ◽  
Author(s):  
Michelle E. Farrell ◽  
Kristen M. Kennedy ◽  
Karen M. Rodrigue ◽  
Gagan S. Wig ◽  
Gérard N. Bischof ◽  
...  
2016 ◽  
Vol 12 ◽  
pp. P100-P100
Author(s):  
Michelle E. Farrell ◽  
Kristen M. Kennedy ◽  
Karen M. Rodrigue ◽  
Gagan S. Wig ◽  
Gérard N. Bischof ◽  
...  

2017 ◽  
Vol 61 (2) ◽  
pp. 689-703 ◽  
Author(s):  
Natalia Valech ◽  
Adrià Tort-Merino ◽  
Nina Coll-Padrós ◽  
Jaume Olives ◽  
María León ◽  
...  

2014 ◽  
Vol 24 (2) ◽  
pp. 117-121
Author(s):  
P Gil-Gregorio ◽  
R Yubero-Pancorbo

SummaryRecently, diagnostic criteria for preclinical Alzheimer's disease have been proposed. These describe and define three stages of disease. Stage I is focused on asymptomatic cerebral amyloidosis. Stage II includes evidence of synaptic dysfunction and/or early degeneration. Finally, stage III of the disease is characterized by the beginning of cognitive decline.


2020 ◽  
pp. 096228022094809
Author(s):  
Hong Li ◽  
Andreana Benitez ◽  
Brian Neelon

Alzheimer’s disease is the leading cause of dementia among adults aged 65 or above. Alzheimer’s disease is characterized by a change point signaling a sudden and prolonged acceleration in cognitive decline. The timing of this change point is of clinical interest because it can be used to establish optimal treatment regimens and schedules. Here, we present a Bayesian hierarchical change point model with a parameter constraint to characterize the rate and timing of cognitive decline among Alzheimer’s disease patients. We allow each patient to have a unique random intercept, random slope before the change point, random change point time, and random slope after the change point. The difference in slope before and after a change point is constrained to be nonpositive, and its parameter space is partitioned into a null region (representing normal aging) and a rejection region (representing accelerated decline). Using the change point time, the estimated slope difference, and the threshold of the null region, we are able to (1) distinguish normal aging patients from those with accelerated cognitive decline, (2) characterize the rate and timing for patients experiencing cognitive decline, and (3) predict personalized risk of progression to dementia due to Alzheimer’s disease. We apply the approach to data from the Religious Orders Study, a national cohort study of aging Catholic nuns, priests, and lay brothers.


Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 320-335 ◽  
Author(s):  
Tobey J Betthauser ◽  
Rebecca L Koscik ◽  
Erin M Jonaitis ◽  
Samantha L Allison ◽  
Karly A Cody ◽  
...  

Abstract This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified groups in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer’s Prevention. One hundred and sixty-seven initially unimpaired individuals (baseline age 59 ± 6 years; 115 females) were stratified by elevated amyloid-β and tau status based on 11C-Pittsburgh compound B (PiB) and 18F-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differed between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between 18F-MK-6240, 11C-PiB, and age. A significant group × age interaction was observed with post hoc comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust against various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did not differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry. Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and 18F-MK-6240 in tangle-associated regions, which were negligible after adjusting for 11C-PiB. Strong associations, particularly in entorhinal cortex, hippocampus and amygdala, were observed between 18F-MK-6240 and global 11C-PiB in regions associated with Braak neurofibrillary tangle stages I–VI. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer’s disease during late middle-age. Within the Alzheimer’s disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. 18F-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer’s disease.


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