Skip to main content
Top
Published in: BMC Geriatrics 1/2017

Open Access 01-12-2017 | Research Article

Associations between cerebral amyloid and changes in cognitive function and falls risk in subcortical ischemic vascular cognitive impairment

Authors: Elizabeth Dao, John R. Best, Ging-Yuek Robin Hsiung, Vesna Sossi, Claudia Jacova, Roger Tam, Teresa Liu-Ambrose

Published in: BMC Geriatrics | Issue 1/2017

Login to get access

Abstract

Background

To determine the association between amyloid-beta (Aβ) plaque deposition and changes in global cognition, executive functions, information processing speed, and falls risk over a 12-month period in older adults with a primary clinical diagnosis of subcortical ischemic vascular cognitive impairment (SIVCI).

Methods

This is a secondary analysis of data acquired from a subset of participants (N = 22) who were enrolled in a randomized controlled trial of aerobic exercise (NCT01027858). The subset of individuals completed an 11C Pittsburgh compound B (PIB) scan. Cognitive function and falls risk were assessed at baseline, 6-months, and 12-months. Global cognition, executive functions, and information processing speed were measured using: 1) ADAS-Cog; 2) Trail Making Test; 3) Digit Span Test; 4) Stroop Test, and 5) Digit Symbol Substitution Test. Falls risk was measured using the Physiological Profile Assessment. Hierarchical multiple linear regression analyses determined the unique contribution of Aβ on changes in cognitive function and falls risk at 12-months after controlling for experimental group (i.e. aerobic exercise training or usual care control) and baseline performance. To correct for multiple comparisons, we applied the Benjamini-Hochberg procedure to obtain a false discovery rate corrected threshold using alpha = 0.05.

Results

Higher PIB retention was significantly associated with greater decrements in set shifting (Trail Making Test, adjusted R2 = 35.3%, p = 0.002), attention and conflict resolution (Stroop Test, adjusted R2 = 33.4%, p = 0.01), and information processing speed (Digit Symbol Substitution Test, adjusted R2 = 24.4%, p = 0.001) over a 12-month period. Additionally, higher PIB retention was significantly associated with increased falls risk (Physiological Profile Assessment, adjusted R2 = 49.1%, p = 0.04). PIB retention was not significantly associated with change in ADAS-Cog and Verbal Digit Span Test (p > 0.05).

Conclusions

Symptoms associated with SIVCI may be amplified by secondary Aβ pathology.

Trial registration

ClinicalTrials.gov, NCT01027858, December 7, 2009.
Literature
1.
go back to reference Jellinger KA, Attems J. Prevalence of dementia disorders in the oldest-old: an autopsy study. Acta Neuropathol. 2010;119(4):421–33.CrossRefPubMed Jellinger KA, Attems J. Prevalence of dementia disorders in the oldest-old: an autopsy study. Acta Neuropathol. 2010;119(4):421–33.CrossRefPubMed
2.
go back to reference Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69(24):2197–204.CrossRefPubMed Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69(24):2197–204.CrossRefPubMed
4.
go back to reference Rockwood K, Macknight C, Wentzel C, Black S, Bouchard R, Gauthier S, et al. The diagnosis of "mixed" dementia in the consortium for the investigation of vascular impairment of cognition (CIVIC). Ann N Y Acad Sci. 2000;903:522–8. Rockwood K, Macknight C, Wentzel C, Black S, Bouchard R, Gauthier S, et al. The diagnosis of "mixed" dementia in the consortium for the investigation of vascular impairment of cognition (CIVIC). Ann N Y Acad Sci. 2000;903:522–8.
5.
go back to reference Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD. Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer's disease. Lancet. 1999;354(9182):919–20.CrossRefPubMed Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD. Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer's disease. Lancet. 1999;354(9182):919–20.CrossRefPubMed
6.
go back to reference Nagy Z, Esiri MM, Jobst KA, Morris JH, King EM, McDonald B, et al. The effects of additional pathology on the cognitive deficit in Alzheimer disease. J Neuropathol Exp Neurol. 1997;56(2):165–70. Nagy Z, Esiri MM, Jobst KA, Morris JH, King EM, McDonald B, et al. The effects of additional pathology on the cognitive deficit in Alzheimer disease. J Neuropathol Exp Neurol. 1997;56(2):165–70.
7.
go back to reference Kalaria RN. The role of cerebral ischemia in Alzheimer's disease. Neurobiol Aging. 2000;21(2):321–30.CrossRefPubMed Kalaria RN. The role of cerebral ischemia in Alzheimer's disease. Neurobiol Aging. 2000;21(2):321–30.CrossRefPubMed
8.
9.
go back to reference Marnane M, Hsiung GY. Could better phenotyping small vessel disease provide new insights into Alzheimer disease and improve clinical trial outcomes? Curr Alzheimer Res. 2016;13(7):750–63.CrossRefPubMed Marnane M, Hsiung GY. Could better phenotyping small vessel disease provide new insights into Alzheimer disease and improve clinical trial outcomes? Curr Alzheimer Res. 2016;13(7):750–63.CrossRefPubMed
10.
go back to reference Park JH, Seo SW, Kim C, Kim SH, Kim GH, Kim ST, et al. Effects of cerebrovascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment. Neurobiol Aging. 2014;35(1):254–60.CrossRefPubMed Park JH, Seo SW, Kim C, Kim SH, Kim GH, Kim ST, et al. Effects of cerebrovascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment. Neurobiol Aging. 2014;35(1):254–60.CrossRefPubMed
11.
go back to reference Lee MJ, Seo SW, Na DL, Kim C, Park JH, Kim GH, et al. Synergistic effects of ischemia and beta-amyloid burden on cognitive decline in patients with subcortical vascular mild cognitive impairment. JAMA psychiatry. 2014;71(4):412–22. Lee MJ, Seo SW, Na DL, Kim C, Park JH, Kim GH, et al. Synergistic effects of ischemia and beta-amyloid burden on cognitive decline in patients with subcortical vascular mild cognitive impairment. JAMA psychiatry. 2014;71(4):412–22.
12.
go back to reference Dao E, Hsiung GY, Sossi V, Jacova C, Tam R, Dinelle K, et al. Exploring the effects of coexisting amyloid in subcortical vascular cognitive impairment. BMC Neurol. 2015;15:197. Dao E, Hsiung GY, Sossi V, Jacova C, Tam R, Dinelle K, et al. Exploring the effects of coexisting amyloid in subcortical vascular cognitive impairment. BMC Neurol. 2015;15:197.
13.
go back to reference Pike KE, Savage G, Villemagne VL, Ng S, Moss SA, Maruff P, et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain : a journal of neurology. 2007;130(Pt 11):2837–44. Pike KE, Savage G, Villemagne VL, Ng S, Moss SA, Maruff P, et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain : a journal of neurology. 2007;130(Pt 11):2837–44.
14.
go back to reference Rosenberg PB, Wong DF, Edell SL, Ross JS, Joshi AD, Brašić JR, et al. Cognition and amyloid load in Alzheimer disease imaged with florbetapir F 18(AV-45) positron emission tomography. Am J Geriatr Psychiatry. 2013;21(3):272–8. Rosenberg PB, Wong DF, Edell SL, Ross JS, Joshi AD, Brašić JR, et al. Cognition and amyloid load in Alzheimer disease imaged with florbetapir F 18(AV-45) positron emission tomography. Am J Geriatr Psychiatry. 2013;21(3):272–8.
15.
go back to reference Weintraub S, Wicklund AH, Salmon DP. The neuropsychological profile of Alzheimer disease. Cold Spring Harbor perspectives in medicine. 2012;2(4):a006171.CrossRefPubMedPubMedCentral Weintraub S, Wicklund AH, Salmon DP. The neuropsychological profile of Alzheimer disease. Cold Spring Harbor perspectives in medicine. 2012;2(4):a006171.CrossRefPubMedPubMedCentral
16.
go back to reference Lim YY, Maruff P, Pietrzak RH, Ames D, Ellis KA, Harrington K, et al. Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer’s disease. Brain : a journal of neurology. 2014;137(1):221–31.CrossRef Lim YY, Maruff P, Pietrzak RH, Ames D, Ellis KA, Harrington K, et al. Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer’s disease. Brain : a journal of neurology. 2014;137(1):221–31.CrossRef
17.
go back to reference Small GW, Siddarth P, Kepe V, et al. Prediction of cognitive decline by positron emission tomography of brain amyloid and tau. Arch Neurol. 2012;69(2):215–22.CrossRefPubMedPubMedCentral Small GW, Siddarth P, Kepe V, et al. Prediction of cognitive decline by positron emission tomography of brain amyloid and tau. Arch Neurol. 2012;69(2):215–22.CrossRefPubMedPubMedCentral
18.
go back to reference Del Campo N, Payoux P, Djilali A, Delrieu J, Hoogendijk EO, Rolland Y, et al. Relationship of regional brain beta-amyloid to gait speed. Neurology. 2016;86(1):36–43.CrossRefPubMedPubMedCentral Del Campo N, Payoux P, Djilali A, Delrieu J, Hoogendijk EO, Rolland Y, et al. Relationship of regional brain beta-amyloid to gait speed. Neurology. 2016;86(1):36–43.CrossRefPubMedPubMedCentral
19.
go back to reference Nadkarni NK, Perera S, Snitz BE, Mathis CA, Price J, Williamson JD, et al. Association of brain amyloid-beta with slow gait in elderly individuals without dementia: influence of cognition and apolipoprotein E epsilon4 genotype. JAMA neurology. 2017;74(1):82–90. Nadkarni NK, Perera S, Snitz BE, Mathis CA, Price J, Williamson JD, et al. Association of brain amyloid-beta with slow gait in elderly individuals without dementia: influence of cognition and apolipoprotein E epsilon4 genotype. JAMA neurology. 2017;74(1):82–90.
20.
go back to reference Wennberg AMV, Savica R, Hagen CE, Roberts RO, Knopman DS, Hollman JH, Vemuri P, Jack CR, Petersen RC, Mielke MM. Cerebral Amyloid Deposition Is Associated with Gait Parameters in the Mayo Clinic Study of Aging. J Am Geriatr Soc. 2017;65(4):792–9. Wennberg AMV, Savica R, Hagen CE, Roberts RO, Knopman DS, Hollman JH, Vemuri P, Jack CR, Petersen RC, Mielke MM. Cerebral Amyloid Deposition Is Associated with Gait Parameters in the Mayo Clinic Study of Aging. J Am Geriatr Soc. 2017;65(4):792–9.
21.
go back to reference Stark SL, Roe CM, Grant EA, Hollingsworth H, Benzinger TL, Fagan AM, et al. Preclinical Alzheimer disease and risk of falls. Neurology. 2013;81(5):437–43. Stark SL, Roe CM, Grant EA, Hollingsworth H, Benzinger TL, Fagan AM, et al. Preclinical Alzheimer disease and risk of falls. Neurology. 2013;81(5):437–43.
22.
go back to reference Lee JH, Kim SH, Kim GH, Seo SW, Park HK, Oh SJ, et al. Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B. Neurology. 2011;77(1):18–25. Lee JH, Kim SH, Kim GH, Seo SW, Park HK, Oh SJ, et al. Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B. Neurology. 2011;77(1):18–25.
23.
go back to reference Ye BS, Seo SW, Kim JH, Kim GH, Cho H, Noh Y, et al. Effects of amyloid and vascular markers on cognitive decline in subcortical vascular dementia. Neurology. 2015;85(19):1687–93.CrossRefPubMedPubMedCentral Ye BS, Seo SW, Kim JH, Kim GH, Cho H, Noh Y, et al. Effects of amyloid and vascular markers on cognitive decline in subcortical vascular dementia. Neurology. 2015;85(19):1687–93.CrossRefPubMedPubMedCentral
24.
go back to reference Liu-Ambrose T, Eng JJ, Boyd LA, Jacova C, Davis JC, Bryan S, et al. Promotion of the mind through exercise (PROMoTE): a proof-of-concept randomized controlled trial of aerobic exercise training in older adults with vascular cognitive impairment. BMC Neurol. 2010;10:14. Liu-Ambrose T, Eng JJ, Boyd LA, Jacova C, Davis JC, Bryan S, et al. Promotion of the mind through exercise (PROMoTE): a proof-of-concept randomized controlled trial of aerobic exercise training in older adults with vascular cognitive impairment. BMC Neurol. 2010;10:14.
25.
go back to reference Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke network vascular cognitive impairment harmonization standards. Stroke. 2006;37(9):2220–41.CrossRefPubMed Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke network vascular cognitive impairment harmonization standards. Stroke. 2006;37(9):2220–41.CrossRefPubMed
26.
go back to reference Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–9. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–9.
27.
go back to reference Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.
28.
go back to reference Kirk A. Target symptoms and outcome measures: cognition. Canad J Neurol Sci. 2007;34(Suppl 1):S42–6.CrossRefPubMed Kirk A. Target symptoms and outcome measures: cognition. Canad J Neurol Sci. 2007;34(Suppl 1):S42–6.CrossRefPubMed
29.
go back to reference Spreen O, Strauss E. A compendium of neuropsychological tests: Administration, norms and commentary. 2nd ed. New York: Oxford University Press; 1998. Spreen O, Strauss E. A compendium of neuropsychological tests: Administration, norms and commentary. 2nd ed. New York: Oxford University Press; 1998.
30.
go back to reference Wechsler D. Wechsler Adult Intelligence Scale—Revised. New York: The Psychological Corporation, Harcourt Brace Jovanovich; 1981. Wechsler D. Wechsler Adult Intelligence Scale—Revised. New York: The Psychological Corporation, Harcourt Brace Jovanovich; 1981.
31.
go back to reference Graf P, Uttl B, Tuokko H. Color- and picture-word Stroop tests: Performance changes in old age. J Clin Exp Neuropsychol. 1995;17(3):390–415. Graf P, Uttl B, Tuokko H. Color- and picture-word Stroop tests: Performance changes in old age. J Clin Exp Neuropsychol. 1995;17(3):390–415.
32.
go back to reference Lord SR, Menz HB, Tiedemann A. A physiological profile approach to falls risk assessment and prevention. Phys Ther. 2003;83(3):237–52.PubMed Lord SR, Menz HB, Tiedemann A. A physiological profile approach to falls risk assessment and prevention. Phys Ther. 2003;83(3):237–52.PubMed
33.
go back to reference Lord SR, Castell S. Physical activity program for older persons: effect on balance, strength, neuromuscular control, and reaction time. Arch Phys Med Rehabil. 1994;75(6):648–52.CrossRefPubMed Lord SR, Castell S. Physical activity program for older persons: effect on balance, strength, neuromuscular control, and reaction time. Arch Phys Med Rehabil. 1994;75(6):648–52.CrossRefPubMed
34.
go back to reference Lord SR, Clark RD, Webster IW. Physiological factors associated with falls in an elderly population. J Am Geriatr Soc. 1991;39(12):1194–200.CrossRefPubMed Lord SR, Clark RD, Webster IW. Physiological factors associated with falls in an elderly population. J Am Geriatr Soc. 1991;39(12):1194–200.CrossRefPubMed
35.
go back to reference Lord SR, Ward JA, Williams P, Anstey KJ. Physiological factors associated with falls in older community-dwelling women. J Am Geriatr Soc. 1994;42(10):1110–7.CrossRefPubMed Lord SR, Ward JA, Williams P, Anstey KJ. Physiological factors associated with falls in older community-dwelling women. J Am Geriatr Soc. 1994;42(10):1110–7.CrossRefPubMed
36.
go back to reference Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2007;27(9):1533–9.CrossRef Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2007;27(9):1533–9.CrossRef
37.
go back to reference Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL. Distribution volume ratios without blood sampling from graphical analysis of PET data. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 1996;16(5):834–40.CrossRef Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL. Distribution volume ratios without blood sampling from graphical analysis of PET data. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 1996;16(5):834–40.CrossRef
38.
go back to reference Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(−)-cocaine PET studies in human subjects. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 1990;10(5):740–7. Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(−)-cocaine PET studies in human subjects. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 1990;10(5):740–7.
39.
go back to reference Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, et al. Simplified quantification of Pittsburgh compound B amyloid imaging PET studies: a comparative analysis. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2005;46(12):1959–72. Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, et al. Simplified quantification of Pittsburgh compound B amyloid imaging PET studies: a comparative analysis. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2005;46(12):1959–72.
40.
go back to reference Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh compound-B. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2005;25(11):1528–47. Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh compound-B. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2005;25(11):1528–47.
41.
go back to reference Collins DL, Neelin P, Peters TM, Evans AC. Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr. 1994;18(2):192–205.CrossRefPubMed Collins DL, Neelin P, Peters TM, Evans AC. Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr. 1994;18(2):192–205.CrossRefPubMed
42.
go back to reference Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995;57(1):289–300. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995;57(1):289–300.
43.
go back to reference Miyake A, Friedman NP, Emerson MJ, Witzki AH, Howerter A, Wager TD. The unity and diversity of executive functions and their contributions to complex "frontal lobe" tasks: a latent variable analysis. Cogn Psychol. 2000;41(1):49–100.CrossRefPubMed Miyake A, Friedman NP, Emerson MJ, Witzki AH, Howerter A, Wager TD. The unity and diversity of executive functions and their contributions to complex "frontal lobe" tasks: a latent variable analysis. Cogn Psychol. 2000;41(1):49–100.CrossRefPubMed
44.
go back to reference Horikawa E, Matsui T, Arai H, Seki T, Iwasaki K, Sasaki H. Risk of falls in Alzheimer's disease: a prospective study. Intern Med. 2005;44(7):717–21.CrossRefPubMed Horikawa E, Matsui T, Arai H, Seki T, Iwasaki K, Sasaki H. Risk of falls in Alzheimer's disease: a prospective study. Intern Med. 2005;44(7):717–21.CrossRefPubMed
45.
go back to reference Suttanon P, Hill KD, Said CM, Logiudice D, Lautenschlager NT, Dodd KJ. Balance and mobility dysfunction and falls risk in older people with mild to moderate Alzheimer disease. American journal of physical medicine & rehabilitation / Association of Academic Physiatrists. 2012;91(1):12–23.CrossRef Suttanon P, Hill KD, Said CM, Logiudice D, Lautenschlager NT, Dodd KJ. Balance and mobility dysfunction and falls risk in older people with mild to moderate Alzheimer disease. American journal of physical medicine & rehabilitation / Association of Academic Physiatrists. 2012;91(1):12–23.CrossRef
46.
go back to reference van Iersel MB, Kessels RP, Bloem BR, Verbeek AL, Olde Rikkert MG. Executive functions are associated with gait and balance in community-living elderly people. J Gerontol Ser A Biol Med Sci. 2008;63(12):1344–9. van Iersel MB, Kessels RP, Bloem BR, Verbeek AL, Olde Rikkert MG. Executive functions are associated with gait and balance in community-living elderly people. J Gerontol Ser A Biol Med Sci. 2008;63(12):1344–9. 
47.
go back to reference Liu-Ambrose T, Nagamatsu LS, Hsu CL, Bolandzadeh N. Emerging concept: 'central benefit model' of exercise in falls prevention. Br J Sports Med. 2013;47(2):115–7.CrossRefPubMed Liu-Ambrose T, Nagamatsu LS, Hsu CL, Bolandzadeh N. Emerging concept: 'central benefit model' of exercise in falls prevention. Br J Sports Med. 2013;47(2):115–7.CrossRefPubMed
Metadata
Title
Associations between cerebral amyloid and changes in cognitive function and falls risk in subcortical ischemic vascular cognitive impairment
Authors
Elizabeth Dao
John R. Best
Ging-Yuek Robin Hsiung
Vesna Sossi
Claudia Jacova
Roger Tam
Teresa Liu-Ambrose
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2017
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-017-0522-4

Other articles of this Issue 1/2017

BMC Geriatrics 1/2017 Go to the issue