Abstract
Objectives: Secondary prevention trials in subjects with preclinical Alzheimer disease may require documentation of brain amyloidosis. The identification of inexpensive and noninvasive screening variables that can identify individuals who have significant amyloid accumulation would reduce screening costs. Methods: A total of 483 cognitively normal (CN) individuals, aged 70-92 years, from the population-based Mayo Clinic Study of Aging, underwent Pittsburgh compound B (PiB)-PET imaging. Logistic regression determined whether age, sex, APOE genotype, family history, or cognitive performance was associated with odds of a PiB retention ratio <1.4 and <1.5. Area under the receiver operating characteristic curve (AUROC) evaluated the discrimination between PiBpositive and -negative subjects. For each characteristic, we determined the number needed to screen in each age group (70-79 and 80-89) to identify 100 participants with PiB <1.4 or <1.5. Results: A total of 211 (44%) individuals had PiB <1.4 and 151 (31%) <1.5. In univariate and multivariate models, discrimination was modest (AUROC ̃0.6-0.7). Multivariately, age and APOE best predicted odds of PiB <1.4 and <1.5. Subjective memory complaints were similar to cognitive test performance in predicting PiB <1.5. Indicators of PiB positivity varied with age. Screening APOE ε4 carriers alone reduced the number needed to screen to enroll 100 subjects with PIB <1.5 by 48% in persons aged 70-79 and 33% in those aged 80-89. Conclusions: Age and APOE genotype are useful predictors of the likelihood of significant amyloid accumulation, but discrimination is modest. Nonetheless, these results suggest that inexpensive and noninvasive measures could significantly reduce the number of CN individuals needed to screen to enroll a given number of amyloid-positive subjects.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1570-1577 |
| Number of pages | 8 |
| Journal | Neurology |
| Volume | 79 |
| Issue number | 15 |
| DOIs | |
| State | Published - Oct 9 2012 |
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ASJC Scopus subject areas
- Clinical Neurology
- Arts and Humanities (miscellaneous)
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Indicators of amyloid burden in a population-based study of cognitively normal elderly. / Mielke, Michelle M; Wiste, Heather J.; Weigand, Stephen D.; Knopman, David S; Lowe, Val; Roberts, Rosebud O; Geda, Yonas Endale; Swenson-Dravis, Dana M.; Boeve, Bradley F; Senjem, Matthew L.; Vemuri, Prashanthi D; Petersen, Ronald Carl; Jack, Clifford R Jr.
In: Neurology, Vol. 79, No. 15, 09.10.2012, p. 1570-1577.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Indicators of amyloid burden in a population-based study of cognitively normal elderly
AU - Mielke, Michelle M
AU - Wiste, Heather J.
AU - Weigand, Stephen D.
AU - Knopman, David S
AU - Lowe, Val
AU - Roberts, Rosebud O
AU - Geda, Yonas Endale
AU - Swenson-Dravis, Dana M.
AU - Boeve, Bradley F
AU - Senjem, Matthew L.
AU - Vemuri, Prashanthi D
AU - Petersen, Ronald Carl
AU - Jack, Clifford R Jr.
PY - 2012/10/9
Y1 - 2012/10/9
N2 - Objectives: Secondary prevention trials in subjects with preclinical Alzheimer disease may require documentation of brain amyloidosis. The identification of inexpensive and noninvasive screening variables that can identify individuals who have significant amyloid accumulation would reduce screening costs. Methods: A total of 483 cognitively normal (CN) individuals, aged 70-92 years, from the population-based Mayo Clinic Study of Aging, underwent Pittsburgh compound B (PiB)-PET imaging. Logistic regression determined whether age, sex, APOE genotype, family history, or cognitive performance was associated with odds of a PiB retention ratio <1.4 and <1.5. Area under the receiver operating characteristic curve (AUROC) evaluated the discrimination between PiBpositive and -negative subjects. For each characteristic, we determined the number needed to screen in each age group (70-79 and 80-89) to identify 100 participants with PiB <1.4 or <1.5. Results: A total of 211 (44%) individuals had PiB <1.4 and 151 (31%) <1.5. In univariate and multivariate models, discrimination was modest (AUROC ̃0.6-0.7). Multivariately, age and APOE best predicted odds of PiB <1.4 and <1.5. Subjective memory complaints were similar to cognitive test performance in predicting PiB <1.5. Indicators of PiB positivity varied with age. Screening APOE ε4 carriers alone reduced the number needed to screen to enroll 100 subjects with PIB <1.5 by 48% in persons aged 70-79 and 33% in those aged 80-89. Conclusions: Age and APOE genotype are useful predictors of the likelihood of significant amyloid accumulation, but discrimination is modest. Nonetheless, these results suggest that inexpensive and noninvasive measures could significantly reduce the number of CN individuals needed to screen to enroll a given number of amyloid-positive subjects.
AB - Objectives: Secondary prevention trials in subjects with preclinical Alzheimer disease may require documentation of brain amyloidosis. The identification of inexpensive and noninvasive screening variables that can identify individuals who have significant amyloid accumulation would reduce screening costs. Methods: A total of 483 cognitively normal (CN) individuals, aged 70-92 years, from the population-based Mayo Clinic Study of Aging, underwent Pittsburgh compound B (PiB)-PET imaging. Logistic regression determined whether age, sex, APOE genotype, family history, or cognitive performance was associated with odds of a PiB retention ratio <1.4 and <1.5. Area under the receiver operating characteristic curve (AUROC) evaluated the discrimination between PiBpositive and -negative subjects. For each characteristic, we determined the number needed to screen in each age group (70-79 and 80-89) to identify 100 participants with PiB <1.4 or <1.5. Results: A total of 211 (44%) individuals had PiB <1.4 and 151 (31%) <1.5. In univariate and multivariate models, discrimination was modest (AUROC ̃0.6-0.7). Multivariately, age and APOE best predicted odds of PiB <1.4 and <1.5. Subjective memory complaints were similar to cognitive test performance in predicting PiB <1.5. Indicators of PiB positivity varied with age. Screening APOE ε4 carriers alone reduced the number needed to screen to enroll 100 subjects with PIB <1.5 by 48% in persons aged 70-79 and 33% in those aged 80-89. Conclusions: Age and APOE genotype are useful predictors of the likelihood of significant amyloid accumulation, but discrimination is modest. Nonetheless, these results suggest that inexpensive and noninvasive measures could significantly reduce the number of CN individuals needed to screen to enroll a given number of amyloid-positive subjects.
UR - http://www.scopus.com/inward/record.url?scp=84867528523&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867528523&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e31826e2696
DO - 10.1212/WNL.0b013e31826e2696
M3 - Article
C2 - 22972644
AN - SCOPUS:84867528523
VL - 79
SP - 1570
EP - 1577
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 15
ER -