Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-28T01:34:29.789Z Has data issue: false hasContentIssue false
  • English
  • Français

Multiple Pathologies are Common in Alzheimer Patients in Clinical Trials

Published online by Cambridge University Press:  02 December 2014

B. W. Wang ,
E. Lu ,
I. R. A. Mackenzie ,
M. Assaly ,
C. Jacova ,
P. E. Lee ,
B. L. Beattie  and
G. Y. R. Hsiung
B. W. Wang
Affiliation:
Department of Medicine, Faculty of Medicine, University of British Columbia
E. Lu
Affiliation:
Department of Medicine, Faculty of Medicine, University of British Columbia
I. R. A. Mackenzie
Affiliation:
Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada
M. Assaly
Affiliation:
Department of Medicine, Faculty of Medicine, University of British Columbia
C. Jacova
Affiliation:
Department of Medicine, Faculty of Medicine, University of British Columbia
P. E. Lee
Affiliation:
Department of Medicine, Faculty of Medicine, University of British Columbia
B. L. Beattie
Affiliation:
Department of Medicine, Faculty of Medicine, University of British Columbia
G. Y. R. Hsiung*
Affiliation:
Department of Medicine, Faculty of Medicine, University of British Columbia
*
Division of Neurology, Room S162, 2211 Wesbrook Mall, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada. Email: hsiung@mail.ubc.ca
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective:

To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology.

Methods:

We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology.

Results:

Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02).

Conclusion:

While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 5 , September 2012 , pp. 592 - 599
Copyright
Copyright © The Canadian Journal of Neurological 2012

References

1.Schneider, JA, Arvanitakis, Z, Bang, W, et al.Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69(24):2197–204.Google Scholar
2.Kovacs, GG, Alafuzoff, I, Al-Sarraj, S, et al.Mixed brain pathologies in dementia: the BrainNet Europe consortium experience. Dement Geriatr Cogn Disord. 2008;26(4):343–50.Google Scholar
3.Sonnen, JA, Santa Cruz, K, Hemmy, LS, et al.Ecology of the aging human brain. Arch Neurol. 2011;68(8):1049–56.Google Scholar
4.O’Brien, JT, Erkinjuntti, T, Reisberg, B, et al.Vascular cognitive impairment. Lancet Neurol. 2003;2(2):89–98.Google Scholar
5.McKeith, I, Mintzer, J, Aarsland, D, et al.Dementia with Lewy bodies. Lancet Neurol. 2004;3(1):19–28.Google Scholar
6.Dubois, B, Feldman, HH, Jacova, C, et al.Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010;9(11): 1118–27.Google Scholar
7.Holmes, C, Boche, D, Wilkinson, D, et al.Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet. 2008;372 (9634):216–23.Google Scholar
8.Alafuzoff, I, Helisalmi, S, Heinonen, EH, et al.Selegiline treatment and the extent of degenerative changes in brain tissue of patients with Alzheimer’s disease. Eur J Clin Pharmacol. 2000;55(11-12):815–19.CrossRefGoogle ScholarPubMed
9.McKhann, G, Drachman, D, Folstein, M, et al.Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984; 34(7):939–44.Google Scholar
10.Gelinas, I, Gauthier, L, McIntyre, M, et al.Development of a functional measure for persons with Alzheimer’s disease: the disability assessment for dementia. Am J Occup Ther. 1999;53 (5):471–81.Google Scholar
11.Lanctot, KL, Hsiung, GY, Feldman, HH, et al.Assessing the validity of deriving clinical dementia rating (CDR) global scores from independently-obtained functional rating scale (FRS) scores in vascular dementia with and without Alzheimer’s disease. Int J Geriatr Psychiatry. 2009;24(10):1174–6.Google Scholar
12.Feldman, H, Levy, AR, Hsiung, GY, et al.A Canadian Cohort study of Cognitive Impairment and Related Dementias (ACCORD): study methods and baseline results. Neuroepidemiology. 2003; 22:265–74.Google Scholar
13.Woodward, M, Mackenzie, IRA, Hsiung, GY, et al.Multiple brain pathologies in dementia are common. Eur Geriatr Med. 2010;1: 259–65.Google Scholar
14.Wisniewski, HM, Silverman, W.Diagnostic criteria for the neuropathological assessment of Alzheimer’s disease: current status and major issues. Neurobiol Aging. 1997;18(4 suppl): s43–50.Google Scholar
15.Newell, KL, Hyman, BT, Growdon, JH, et al.Application of the National Institute on Aging (NIA)-Reagan Institute criteria for the neuropathological diagnosis of Alzheimer disease. J Neuropathol Experimental Neurol. 1999;58(11):1147–55.Google Scholar
16.McKeith, IG, Fairbairn, AF, Bothwell, RA, et al.An evaluation of the predictive validity and inter-rater reliability of clinical diagnostic criteria for senile dementia of Lewy body type. Neurology. 1994;44(5):872–7.Google Scholar
17.Munoz, DG.The pathological basis of multi-infarct dementia. Alzheimer Dis Assoc Disord. 1991;5(2):77–90.Google Scholar
18.Jellinger, KA, Attems, J.Is there pure vascular dementia in old age? J Neurol Sci. 2010;299(1-2):150–4.Google Scholar
19.Cairns, NJ, Taylor-Reinwald, L, Morris, JC.Autopsy consent, brain collection, and standardized neuropathologic assessment of ADNI participants: the essential role of the neuropathology core Alzheimers Dement. 2010;6(3):274–9.Google Scholar
20.Esiri, MM, Nagy, Z, Smith, MZ, et al.Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer’s disease Lancet. 1999;354(9182):919–20.CrossRefGoogle ScholarPubMed
21.Jellinger, KA, Attems, J.Prevalence and impact of cerebrovascular pathology in Alzheimer’s disease and parkinsonism Acta Neurol Scand. 2006;114(1):3846.Google Scholar
22.Reed, BR, Mungas, DM, Kramer, JH, et al.Profiles of neuropsychological impairment in autopsy-defined Alzheimer’s disease and cerebrovascular disease. Brain. 2007;130(Pt 3): 731–9.Google Scholar
23.McGuinness, B, Barrett, SL, Craig, D, et al.Executive functioning in Alzheimer’s disease and vascular dementia. Int J Geriatr Psychiatry. 2010;25(6):562–8.Google Scholar
24.Baillon, S, Muhommad, S, Marudkar, M, et al.Neuropsychological performance in Alzheimer’s disease and vascular dementia: comparisons in a memory clinic population. Int J Geriatr Psychiatry. 2003;18(7):602–8.Google Scholar
25.Tartaglia, MC, Rosen, HJ, Miller, BL.Neuroimaging in dementia. Neurotherapeutics. 2011;8(1):82–92.Google Scholar
26.Whitwell, JL, Jack, CR Jr., Neuroimaging in dementia. Neurol Clin. 2007;25(3):843, 57, viii.Google Scholar
27.ADVANCE Collaborative Group, Patel, A, MacMahon, S, et al.Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24): 2560–72.Google ScholarPubMed
28.Ligthart, SA, Moll van Charante, EP, Van Gool, WA, et al.Treatment of cardiovascular risk factors to prevent cognitive decline and dementia: a systematic review. Vasc Health Risk Manag. 2010; 7(6):775–85.Google Scholar
29.Shepherd, J, Blauw, GJ, Murphy, MB, et al.Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002 Nov 23;360(9346): 1623–30.Google Scholar
30.Gorelick, P, Scuteri, A, Black, SE, et al.Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2011;42(9):2672–713.Google Scholar
31.Vuorinen, M, solomon, A, Rovio, S, et al.Changes in vascular risk factors from midlife to late life and white matter lesions: a 20-year follow-up study. Dement Geriatr Cogn Disord. 2011;31(2): 119–25.Google Scholar
32.Bombois, S, Maurage, CA, Gompel, M, et al.Absence of beta-amyloid deposits after immunization in Alzheimer disease with Lewy body dementia. Arch Neurol. 2007;64(4):583–7.CrossRefGoogle ScholarPubMed