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Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity.
Biol Psychiatry. 2020 05 01; 87(9):819-828.BP

Abstract

BACKGROUND

Stage 1 of the National Institute on Aging-Alzheimer's Association's proposed Alzheimer's disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention. Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality. We examined whether baseline cognitive performance would predict progression from normal to abnormal levels of Aβ.

METHODS

We examined the association of baseline cognitive composites (Preclinical Alzheimer Cognitive Composite, Alzheimer's Disease Neuroimaging Initiative (ADNI) memory factor composite) with progression to Aβ positivity in 292 nondemented, Aβ-negative ADNI participants. Additional analyses included continuous cerebrospinal fluid biomarker levels to examine the effects of subthreshold pathology.

RESULTS

Forty participants progressed to Aβ positivity during follow-up. Poorer baseline performance on both cognitive measures was significantly associated with increased odds of progression. More abnormal levels of baseline cerebrospinal fluid phosphorylated tau and subthreshold Aβ were associated with increased odds of progression to Aβ positivity. Nevertheless, baseline ADNI memory factor composite performance predicted progression even after controlling for baseline biomarker levels and APOE genotype (Preclinical Alzheimer Cognitive Composite was trend level). Survival analyses were largely consistent: controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to Aβ positivity (ADNI memory factor composite was trend level).

CONCLUSIONS

The possibility of intervening before Aβ reaches pathological levels is of obvious benefit. Low-cost, noninvasive cognitive measures can be informative for determining who is likely to progress to Aβ positivity, even after accounting for baseline subthreshold biomarker levels.

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Authors+Show Affiliations

Elman JA
Department of Psychiatry, University of California, San Diego, California; Center for Behavior Genetics of Aging, University of California, San Diego, California. Electronic address: jaelman@ucsd.edu.
Panizzon MS
Department of Psychiatry, University of California, San Diego, California; Center for Behavior Genetics of Aging, University of California, San Diego, California.
Gustavson DE
Center for Behavior Genetics of Aging, University of California, San Diego, California; Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, Tennessee.
Franz CE
Department of Psychiatry, University of California, San Diego, California; Center for Behavior Genetics of Aging, University of California, San Diego, California.
Sanderson-Cimino ME
Department of Psychiatry, University of California, San Diego, California; Center for Behavior Genetics of Aging, University of California, San Diego, California.
Lyons MJ
Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
Kremen WS
Department of Psychiatry, University of California, San Diego, California; Center for Behavior Genetics of Aging, University of California, San Diego, California; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, California.
Alzheimer’s Disease Neuroimaging Initiative
No affiliation info available

MeSH

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitionCognitive DysfunctionDisease ProgressionHumansNeuropsychological Teststau Proteins

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

32067693

Citation

Elman, Jeremy A., et al. "Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity." Biological Psychiatry, vol. 87, no. 9, 2020, pp. 819-828.
Elman JA, Panizzon MS, Gustavson DE, et al. Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity. Biol Psychiatry. 2020;87(9):819-828.
Elman, J. A., Panizzon, M. S., Gustavson, D. E., Franz, C. E., Sanderson-Cimino, M. E., Lyons, M. J., & Kremen, W. S. (2020). Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity. Biological Psychiatry, 87(9), 819-828. https://doi.org/10.1016/j.biopsych.2019.12.021
Elman JA, et al. Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity. Biol Psychiatry. 2020 05 1;87(9):819-828. PubMed PMID: 32067693.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity. AU - Elman,Jeremy A, AU - Panizzon,Matthew S, AU - Gustavson,Daniel E, AU - Franz,Carol E, AU - Sanderson-Cimino,Mark E, AU - Lyons,Michael J, AU - Kremen,William S, AU - ,, Y1 - 2020/01/07/ PY - 2019/09/05/received PY - 2019/12/19/revised PY - 2019/12/19/accepted PY - 2020/2/19/pubmed PY - 2021/1/7/medline PY - 2020/2/19/entrez KW - AD KW - Alzheimer’s disease KW - Amyloid accumulation KW - Biomarker trajectories KW - Cognition KW - MCI KW - Mild cognitive impairment KW - β-amyloid SP - 819 EP - 828 JF - Biological psychiatry JO - Biol Psychiatry VL - 87 IS - 9 N2 - BACKGROUND: Stage 1 of the National Institute on Aging-Alzheimer's Association's proposed Alzheimer's disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention. Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality. We examined whether baseline cognitive performance would predict progression from normal to abnormal levels of Aβ. METHODS: We examined the association of baseline cognitive composites (Preclinical Alzheimer Cognitive Composite, Alzheimer's Disease Neuroimaging Initiative (ADNI) memory factor composite) with progression to Aβ positivity in 292 nondemented, Aβ-negative ADNI participants. Additional analyses included continuous cerebrospinal fluid biomarker levels to examine the effects of subthreshold pathology. RESULTS: Forty participants progressed to Aβ positivity during follow-up. Poorer baseline performance on both cognitive measures was significantly associated with increased odds of progression. More abnormal levels of baseline cerebrospinal fluid phosphorylated tau and subthreshold Aβ were associated with increased odds of progression to Aβ positivity. Nevertheless, baseline ADNI memory factor composite performance predicted progression even after controlling for baseline biomarker levels and APOE genotype (Preclinical Alzheimer Cognitive Composite was trend level). Survival analyses were largely consistent: controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to Aβ positivity (ADNI memory factor composite was trend level). CONCLUSIONS: The possibility of intervening before Aβ reaches pathological levels is of obvious benefit. Low-cost, noninvasive cognitive measures can be informative for determining who is likely to progress to Aβ positivity, even after accounting for baseline subthreshold biomarker levels. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/32067693/Amyloid_β_Positivity_Predicts_Cognitive_Decline_but_Cognition_Predicts_Progression_to_Amyloid_β_Positivity_ DB - PRIME DP - Unbound Medicine ER -