Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly

Abstract

The relative importance of vascular and Alzheimer's disease (AD) lesions, their interaction in the development of cognitive impairment and the very existence of mixed dementia induced by the potentiation of both mechanisms remain controversial. The aim of this study was to assess whether the patients with infarcts and lacunes have fewer plaques and tangles than those without vascular lesions, for similar severity of clinical dementia. We performed a prospective clinicopathological study in elderly patients of a long-stay care unit. The severity of clinical dementia was assessed by psychometry performed according to standardized methods less than 6 months before death. A volumetric study of cerebral vascular lesions was performed at post-mortem study of the brain. The density of neuritic plaques (SP), Amyloid beta focal deposits (A beta FD), and neurofibrillary tangles (NFT) in the temporal and frontal isocortex was quantified. According to DSM III criteria, 28 of the 33 patients for whom autopsies were performed had dementia. Twenty-four of the included patients had degenerative or vascular lesions, or both. The volume of infarcts and lacunes was significantly correlated with the severity of cognitive impairment. The density of SP, A beta FD and NFT in the temporal and frontal isocortex was significantly lower when vascular lesions were present. For similar clinical severity of dementia, there were fewer AD lesions in patients with vascular lesions than in those without vascular lesions.

Multiple pathologies are common and related to dementia in the oldest-old

“…31 Moreover, in individuals with the same level of cognitive impairment, studies show that those with mixed pathologies have lower levels of AD pathology compared with individuals who have AD pathology alone. [32][33][34] Together, these investigations add further support to the notion that the effect of multiple pathologies may be additive or perhaps may interact in some way.…”

Age effects on atrophy rates of entorhinal cortex and hippocampus

“…Furthermore, since an effect of lacunes on the rate of ERC atrophy was not detectable, our finding suggests that ERC atrophy rate may be more specific for AD pathology than hippocampal atrophy rate. However, AD patients have often co-existing cerebrovascular pathology, and further, AD and cerebrovascular disease may have an additional or even synergetic effect on dementia development [37,58]. Effect of lacunes on hippocampal atrophy rate but not ERC atrophy rate suggests that hippocampal atrophy rate may be a better marker for predicting the onset of dementia in subjects with cerebrovascular diseases than ERC atrophy rate.…”

“…Another risk factor for cognitive impairment, in addition to advanced age, is subcortical cerebral vascular disease, manifested as subcortical infarcts/lacunes and white matter hyperintensities (WMH) on MRI images [8,13,37,46,50,58]. A recent clinical study demonstrated that elderly individuals with silent brain infarcts were at greater risk for dementia and cognitive decline than elderly individuals without such lesions [53].…”

White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy

“…Clinicopathological studies have found that, for any level of cognitive deficit, the density of neuritic plaques and neurofibrillary tangles in the neocortex is Du 4 significantly lower in cases of AD mixed with cerebrovascular disease than in cases of AD without cerebrovascular disease [32,35,40], suggesting that cerebrovascular disease has effects in addition to AD pathology on cognition. Furthermore, Esiri et al found that vascular disease had a greater impact on cognitive performance at early stages of AD than at more advanced AD stages [14].…”