Frequent amyloid deposition without significant cognitive impairment among the elderly

Howard Jay Aizenstein, Robert D. Nebes, Judith A. Saxton, Julie C. Price, Chester A. Mathis, Nicholas D. Tsopelas, Scott K. Ziolko, Jeffrey A. James, Beth E. Snitz, Patricia R. Houck, Wenzhu Bi Mowrey, Ann D. Cohen, Brian J. Lopresti, Steven T. DeKosky, Edythe M. Halligan, William E. Klunk

Research output: Contribution to journalArticle

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Abstract

Objective: To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests. Design: Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs). Setting: University medical center. Participants: From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included. Main Outcome Measures: Regional PiB retention and cognitive test performance. Results: Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. Conclusions: Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.

Original languageEnglish (US)
Pages (from-to)1509-1517
Number of pages9
JournalArchives of Neurology
Volume65
Issue number11
DOIs
StatePublished - Nov 2008
Externally publishedYes

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Amyloid
Alzheimer Disease
Positron-Emission Tomography
Cognition
Cognitive Dysfunction
Cognitive Impairment
Deposition
Pittsburgh
Neuropsychological Tests
Volunteers
Person
Alzheimer's Disease
Imaging
Demography
Outcome Assessment (Health Care)
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Aizenstein, H. J., Nebes, R. D., Saxton, J. A., Price, J. C., Mathis, C. A., Tsopelas, N. D., ... Klunk, W. E. (2008). Frequent amyloid deposition without significant cognitive impairment among the elderly. Archives of Neurology, 65(11), 1509-1517. https://doi.org/10.1001/archneur.65.11.1509

Frequent amyloid deposition without significant cognitive impairment among the elderly. / Aizenstein, Howard Jay; Nebes, Robert D.; Saxton, Judith A.; Price, Julie C.; Mathis, Chester A.; Tsopelas, Nicholas D.; Ziolko, Scott K.; James, Jeffrey A.; Snitz, Beth E.; Houck, Patricia R.; Mowrey, Wenzhu Bi; Cohen, Ann D.; Lopresti, Brian J.; DeKosky, Steven T.; Halligan, Edythe M.; Klunk, William E.

In: Archives of Neurology, Vol. 65, No. 11, 11.2008, p. 1509-1517.

Research output: Contribution to journalArticle

Aizenstein, HJ, Nebes, RD, Saxton, JA, Price, JC, Mathis, CA, Tsopelas, ND, Ziolko, SK, James, JA, Snitz, BE, Houck, PR, Mowrey, WB, Cohen, AD, Lopresti, BJ, DeKosky, ST, Halligan, EM & Klunk, WE 2008, 'Frequent amyloid deposition without significant cognitive impairment among the elderly', Archives of Neurology, vol. 65, no. 11, pp. 1509-1517. https://doi.org/10.1001/archneur.65.11.1509
Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Archives of Neurology. 2008 Nov;65(11):1509-1517. https://doi.org/10.1001/archneur.65.11.1509
Aizenstein, Howard Jay ; Nebes, Robert D. ; Saxton, Judith A. ; Price, Julie C. ; Mathis, Chester A. ; Tsopelas, Nicholas D. ; Ziolko, Scott K. ; James, Jeffrey A. ; Snitz, Beth E. ; Houck, Patricia R. ; Mowrey, Wenzhu Bi ; Cohen, Ann D. ; Lopresti, Brian J. ; DeKosky, Steven T. ; Halligan, Edythe M. ; Klunk, William E. / Frequent amyloid deposition without significant cognitive impairment among the elderly. In: Archives of Neurology. 2008 ; Vol. 65, No. 11. pp. 1509-1517.
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abstract = "Objective: To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests. Design: Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs). Setting: University medical center. Participants: From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included. Main Outcome Measures: Regional PiB retention and cognitive test performance. Results: Of 43 clinically unimpaired elderly persons imaged, 9 (21{\%}) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. Conclusions: Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.",
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AU - Tsopelas, Nicholas D.

AU - Ziolko, Scott K.

AU - James, Jeffrey A.

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AU - Mowrey, Wenzhu Bi

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AU - DeKosky, Steven T.

AU - Halligan, Edythe M.

AU - Klunk, William E.

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