White matter pathology in Alzheimer's disease and vascular dementia: quantification by amyloid‐β precursor protein immunocytochemistry

Abstract

Alzheimer's disease (AD) and vascular dementia (VaD) are two of the common dementias in the elderly. Imaging studies have demonstrated white matter changes of vascular etiology to occur in both disorders. While there have increased efforts to differentiate white matter pathology by quantitative magentic resonance imaging in these disorders there is no clear consensus. We assessed white matter lesions in brains of the first 100 demented patients who came to autopsy from our prospectively evaluated series. We examined the extent of axonal pathology by conventional methods including LFB for myelin, and amyloid‐β precursor protein (AβPP) immunocytochemistry with antibodies to 22C11. AβPP has recently been used to examine axonal injury in head trauma. Our results indicated AβPP reactive accumulation along white matter tracts in the temporal cortex encompassing the hippocampal formation to be common. The highest reactivity was evident in tissue from VaD subjects compared with that from AD or dementia with Lewy bodies (DLB). Compared with conventional myelin stains, AβPP immunocytochemistry was more sensitive to visualize subtle changes. We suggest AβPP immunocytochemistry is a useful index to assess ischaemic white matter lesions to differentiate dementias. Acknowledgements: Supported by the MRC (UK), Alzheimer's Research Trust (UK) and Alzheimer's Association (USA).

White Matter Hyperintensities Are Associated With Impairment of Memory, Attention, and Global Cognitive Performance in Older Stroke Patients

“…31 Severe WHM were associated with global cognitive impairment. These findings are potentially important because they indicate that in stroke patients without dementia, WMH are a substrate of a broad range of core cognitive functions and emphasize the potential value of WMH as a target for preventing dementia in these individuals, with stringent control of blood pressure or cholinergic therapies among the exciting opportunities for clinical trials.…”

NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and without dementia

“…For example, a recent report 25 highlighted the potential importance of concurrent atrophy as an association of dementia in stroke patients and postulated that this may be more important in older patients. Supporting this hypothesis, recent neuropathologic work has indicated greater deposition of amyloid in older compared with younger patients with VaD, 26 suggesting a greater overlap of cerebrovascular and neurodegenerative processes in older individuals. As stroke patients over age 75 are those at greatest risk of dementia, it is important to specifically clarify the substrates of dementia in these patients.…”