Posted by phillipa on September 27, 2012, at 21:03:35
Seems that White Matter Lesions Not Hippocampal Atrophy Predict Alzheimers Disease. Different Diseases Also Predict. Access with Pet Scans. Phillipa
From Medscape Medical News > Neurology
White Matter Lesions, Not Hippocampal Atrophy, Predict AD
Megan Brooks
Authors and Disclosures
September 26, 2012 Regional white matter hyperintensity volume may be a more important predictor of Alzheimer's disease (AD) than hippocampal atrophy, a new study hints.
"Our study suggests that small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI), may contribute to the clinical presentation of AD," Adam M. Brickman, PhD, from the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University in New York City, told Medscape Medical News.
Dr. Adam Brickman
It also suggests that a "high burden of WMHs appears to increase the risk of future dementia better than hippocampus atrophy, traditionally thought of as a radiological marker of the neurodegenerative changes associated with AD," he added.
Their results were published online September 3 in Archives of Neurology.
Implications for Prevention
The findings have clinical implications, particularly for prevention of dementia, Dr. Brickman said.
"Many of the risk factors for small vessel cerebrovascular disease, including hypertension, diabetes, obesity, and others, have been identified. Controlling some of these peripheral vascular factors, either through lifestyle choices, behavioral intervention, or pharmacological treatment, may reduce the risk of small vessel cerebrovascular disease, which, in turn, may reduce the risk for dementia," he explained.
WMH burden, particularly in posterior brain regions, is elevated in individuals at risk for AD and those with AD, and has been shown to predict the rate of cognitive decline in individuals with AD, the authors explain in their article.
Some population-based studies have suggested that WMH burden is associated with future development of AD, yet it is unclear whether this association is independent of "hypothesized biological etiological markers" such as hippocampal atrophy.
Dr. Brickman and colleagues used the Washington Heights/Inwood Columbia Aging Project (WHICAP), an ongoing longitudinal community-based study of aging and dementia in northern Manhattan, in New York City, to investigate.
As part of the study, 717 dementia-free participants underwent MRI between 2005 and 2007; 503 returned an average of 40 months later for follow-up examinations. At this time, 46 met criteria for dementia (27 probable AD, 6 probable AD with stroke, 2 probable AD with Parkinson's disease, and 9 probable AD with other concomitant disease). The remaining patients had Lewy bodies.
The researchers say WMH volume in the parietal lobes predicted time to incident dementia (hazard ratio [HR], 1.194; P = .03), whereas distribution of WMHs in other regions did not.
They calculate that for every every 1 cubic centimeter increase in WMH volume in the parietal lobe there is an associated 19% increase in the risk of incident dementia.
Relative hippocampal volume did not predict dementia when considered alone (HR, 0.419; P = .77) or with WMH volume (HR, 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR, 1.197; P = .049), the researchers say.
"Although previously thought to be of little clinical relevance, WMHs have emerged in recent years as particularly salient radiological correlates of cognitive aging," Dr. Brickman and colleagues conclude. "Our observation that WMHs predict future AD is in line with other recent studies that have shown increased WMHs in prevalent AD and mild cognitive impairment, as well as recent observations that WMHs predict rate of cognitive decline among individuals with prevalent AD."
The fact that their findings were restricted to the parietal lobes "raises questions about the unique role parietal lobe pathology may play in AD," they add.
Parietal Lobe Finding "Novel"
Lisa C. Silbert, MD, from the Layton Aging and Alzheimer's Disease Center and Department of Neurology at Oregon Health and Science University in Portland, agrees. She told Medscape Medical News that the finding that parietal lobe WMHs were most predictive of dementia is "novel and emphasizes the importance of examining regional changes in white matter integrity."
Dr. Silbert, who was not involved in the study, said that overall, she found it "very interesting and definitely unique."
The authors, she explained, were able to examine "a fairly large number of subjects (700+) with MRI until conversion to dementia. Their findings may stem in part by the use of a definition of probable AD that included those with stroke and other pathologies that contribute to dementia (Parkinson's, etc). This likely explains differences in findings from other studies that had more pure AD populations, and thus more hippocampal atrophy."
The importance of this article, Dr. Silbert added, "is in the examination of dementia stemming from mixed pathologies, which in several population-based pathological studies...has been found to be the most common form of dementia (i.e., mixed AD/vascular disease is much more common than dementia from just AD or just vascular disease alone) particularly in older populations."
In their article, Dr. Brickman and colleagues say there are 3 "notable" potential reasons for the negative predictive value of hippocampal atrophy for incident AD in this community-based sample.
First, the sample is older than typical aging and dementia cohorts (mean age, 79.6 years). Within this age group, it is possible that the neurobiological underpinnings of AD are driven primarily by vascular factors rather than neurodegenerative or atrophic changes in the hippocampus.
Second, clinic-based samples often exclude patients with significant vascular disease history; thus, other samples may be restricted to a subset of patients in whom hippocampal atrophy is more relevant.
And third, "cross-sectional calculations of relative hippocampal volume may underestimate or overestimate atrophy particularly among older adults from diverse backgrounds in whom variance in brain morphology may reflect a combination of developmental and degenerative processes," they write.
Dr. Brickman said he and his colleagues will continue to pursue this line of investigation in a number of ways. These include examining the longitudinal progression of WMHs and hippocampus atrophy in relation to the onset of the symptoms of AD and looking at how small vessel cerebrovascular disease interacts with primary AD pathology measured both in vivo and postmortem.
Dr. Silbert said, "An extremely important remaining question is whether or not these findings represent small vessel atherosclerotic disease, amyloid angiopathy, secondary Wallerian degeneration from cortical pathology, or some combination of these etiologies."
The study was supported by grants from the National Institutes of Health. The study authors and Dr. Silbert have disclosed no relevant financial relationships.Arch Neurol. 2012. Published online September 3, 2012.
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