The underdiagnosis of vascular contribution to dementia

The Sieratzki Chair of Neurology, Tel-Aviv University Medical School, Ramat-Aviv 69978, Israel.
Journal of the Neurological Sciences (Impact Factor: 2.47). 04/2005; 229-230:3-6. DOI: 10.1016/j.jns.2004.11.011
Source: PubMed


The existence of vascular dementia (VaD) was first identified by Marie, who described the etat lacunaire, and by Binswanger, who identified white matter lesions in the brain subcortical areas. Alois Alzheimer, when defining the disease now bearing his name, did so in a patient with a presenile onset. The majority of demented elderly people were then believed to have cerebral arteriosclerosis underlying their cognitive decline. The role of cortical vascular lesions, while clear to clinicians, was highlighted only later, by the pathological studies of Tomlinson et al. and the clinical demonstrations of Hachinski et al. who have defined multi-infarct dementia. Lately, the emphasis shifted to pathogenic mechanisms for vascular brain disease with the identification of a multitude of processes, such as lipohyalinosis, cardiac dysfunction and genetic causes, to name only a few. Epidemiologic studies have demonstrated the high frequency of vascular lesions in brains of demented individuals, as well as the fact that vascular factors can contribute to Alzheimer's disease (AD). Moreover, many factors, which were identified as contributing to cerebrovascular disease in general and VaD in particular, are frequently suspected as predisposing to AD as well. All these considerations converge to the realization that vascular components are extremely important in the pathogenesis of old-age dementia and that prevention and perhaps treatment of dementia are within reach. These surprising findings highlight the importance of mixed vascular-degenerative dementia as a disorder that has to be properly defined.

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    • "AD is neuropathologically heterogeneous with differences in cerebovascular disease and reductions in cerebral blood flow (CBF)[3]. VaD is also clinically and pathologically heterogeneous and results from an array of different types of cerebral ischemic disease and damage, many of which coincide with diminished CBF due to abnormal cardiac function[4] [5]. The pathologies of both forms of dementia can co-exist, making differential diagnosis of AD or VaD very challenging, especially in the elderly, so the condition is often referred to as mixed dementia [3] [6] [7]. "
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    ABSTRACT: We investigated whether angiotensin II receptor blockers and angiotensin converting enzyme inhibitors were associated with risk of mortality or inpatient hospitalization for patients with dementia compared to other antihypertensive medications. We extracted a clinical cohort of 6,290 patients with dementia from the United Kingdom General Practice Research Database, prescribed antihypertensive medication at diagnosis of dementia with around 10 years follow-up. Using survival analysis we estimated associations of exposure to antihypertensive medication with subsequent hospitalization and mortality risk, stratified by dementia type (Alzheimer's disease, vascular and other dementias). Angiotensin converting enzyme inhibitors (but not angiotensin II receptor blockers) were associated with an increased risk of mortality in patients with Alzheimer's disease (adjusted hazard ratio: 1.19; 95% CI 1.07, 1.33, p = 0.002), but no convincing evidence of increased hospitalization. Angiotensin II receptor blockers were inversely associated with hospitalization for any form of dementia, but after adjustment for covariates, these associations became consistent with chance. Further evidence is required to either support or refute the observation that exposure to angiotensin converting enzyme inhibitors in patients with dementia is associated with increased mortality.
    Journal of Alzheimer's disease: JAD 10/2012; 33(4). DOI:10.3233/JAD-2012-121090 · 4.15 Impact Factor
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    • "Alzheimer's disease (AD) is among the most common diseases in aging societies, and its prevalence is expected to quadruple by the year 2047. [1] Vascular risk factors and stroke, which are highly prevalent in ageing societies, are clearly associated to a higher risk of vascular dementia (VaD), [2] [3] but are also associated with a higher risk of AD. [4] [5] We previously reported associations of stroke, [6] hyperinsulinemia, [7] diabetes, [8] current smoking, [9] and hypertension, [10] to a higher risk of cognitive impairment or AD. We sought to explore how the presence of vascular risk factors modifies the neuropsychological profile of clinically diagnosed AD. "
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    ABSTRACT: Vascular risk factors increase the risk of Alzheimer's disease (AD). The mechanisms for these associations are unclear, and may be due to misdiagnosis of a vascular dementia syndrome as AD. To examine differences in neuropsychological profile among persons diagnosed clinically with AD with and without vascular risk factors or stroke. Community based cohort study. Individual and composite scores of neuropsychological tests at the time of clinical diagnosis of incident AD were compared among 243 persons with and without vascular risk factors or stroke. Among subjects with incident AD, diabetes was associated with lower performance in Delayed Recall of the Selective Reminding Test (SRT), while persons diagnosed with hypertension scored lower in consistent long term recall (CLTR) of the SRT and current smokers scored lower in Category Fluency. None of the risk factors was associated with differences in composite scores in memory, abstract/visuospatial or language domain, nor was the number of risk factors per person. Persons with stroke had a higher delayed recall score at the time of AD diagnosis. The presence of vascular risk factors among persons with clinically diagnosed AD was associated with subtle differences in neuropsychological profile at the time of diagnosis. This study needs to be replicated in samples with brain imaging, a comprehensive executive abilities battery, and pathological diagnosis of AD.
    Journal of the Neurological Sciences 07/2007; 257(1-2):194-201. DOI:10.1016/j.jns.2007.01.030 · 2.47 Impact Factor
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    ABSTRACT: The purpose of this review is to highlight existing literature on the epidemiology, pathophysiology, and novel risk factors for vascular dementia. We further examine the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular diseases to the development of vascular dementia. In the elderly, in whom cerebral perfusion is diminished by the aging process, additional reduction in cerebral blood flow stemming from exposure to potentially modifiable vascular risk factors increases the probability of developing vascular dementia. Finally, we discuss the association between obstructive sleep apnea, an underrecognized risk factor for stroke, and vascular dementia. Obstructive sleep apnea is linked to cerebrovascular disease through many intermediary vascular risk factors and may directly cause cerebrovascular damage through microvacular disease. Insight into how cardiovascular risk factors induce vascular dementia offers an enhanced understanding of the multifactorial pathophysiology by this disorder and ways of preventing and managing the cerebrovascular precursors of vascular dementia. Many vital questions about the relation of obstructive sleep apnea with stroke and vascular dementia are still unanswered and await future well-designed studies.
    09/2013; 2(3). DOI:10.1007/s13670-013-0054-5
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