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Abstract
Objective: The purpose of this study was to examine the role of multiple pathologies in the expression of dementia in the oldest-old.
Methods: A total of 183 participants of The 90+ Study with longitudinal follow-up and autopsy were included in this clinical-pathologic investigation. Eight pathologic diagnoses (Alzheimer disease [AD], microinfarcts, hippocampal sclerosis, macroinfarcts, Lewy body disease, cerebral amyloid angiopathy, white matter disease, and others) were dichotomized. We estimated the odds of dementia in relation to each individual pathologic diagnosis and to the total number of diagnoses. We also examined dementia severity in relation to number of pathologic diagnoses.
Results: The presence of multiple pathologic diagnoses was common and occurred more frequently in those with dementia compared with those without dementia (45% vs 14%). Higher numbers of pathologic diagnoses were also associated with greater dementia severity. Participants with intermediate/high AD pathology alone were 3 times more likely to have dementia (odds ratio = 3.5), but those with single non-AD pathologies were 12 times more likely to have dementia (odds ratio = 12.4). When a second pathology was present, the likelihood of dementia increased 4-fold in those with intermediate/high AD pathology but did not change in those with non-AD pathologies, suggesting that pathologies may interrelate in different ways.
Conclusions: In the oldest-old, the presence of multiple pathologies is associated with increased likelihood and severity of dementia. The effect of the individual pathologies may be additive or perhaps synergistic and requires further research. Multiple pathologies will need to be targeted to reduce the burden of dementia in the population.
GLOSSARY
- AD=
- Alzheimer disease;
- CAA=
- cerebral amyloid angiopathy;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition);
- H&E=
- hematoxylin & eosin;
- HS=
- hippocampal sclerosis;
- LBD=
- Lewy body disease;
- MMSE=
- Mini-Mental State Examination;
- NIA=
- National Institute on Aging;
- OR=
- odds ratio;
- SAE=
- subcortical arteriolosclerotic leukoencephalopathy;
- UCI=
- University of California, Irvine
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received November 14, 2014.
- Accepted in final form April 14, 2015.
- © 2015 American Academy of Neurology
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