Vascular dementia: Different forms of vessel disorders contribute to the development of dementia in the elderly brain
Highlights
► Vascular dementia is the net results of vascular tissue lesions. ► Vascular and neurodegenerative lesions frequently co-occur in the elderly brain. ► Development of dementia is often due to both pathologies. ► Diagnosis and treatment of coexisting neurodegenerative lesions in vascular dementia.
Introduction
Vascular cognitive impairment (VCI) is a syndrome with evidence of clinical stroke or subclinical vascular brain injury and cognitive impairment affecting at least one cognitive domain. The most severe form of VCI is vascular dementia (VaD) (Gorelick et al., 2011, Roman et al., 1993). Most authors distinguish familial and sporadic forms of VaD (Ferrer, 2010, Gorelick et al., 2011, Ince, 2005, Kalimo and Kalaria, 2005). Familial VaD is usually caused by gene mutations. The most frequent subtype of familial VaD is the “cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy” (CADASIL) (Ferrer, 2010, Gorelick et al., 2011, Kalimo and Kalaria, 2005). However, CADASIL that is caused by mutations in the Notch 3 gene (Joutel et al., 1996) and other types of familial VaD are not within the scope of this article. Here, we want to review the relationship of the three major types of sporadic VaD, i.e. 1. multi infarct dementia, 2. strategic infarct dementia, and 3. subcortical vascular encephalopathy (synonymous with Binswanger's disease) (Ferrer, 2010, Ince, 2005), with their underlying vascular pathologies. In addition, we will discuss VaD overlapping with other age-related pathologies leading to dementia, e.g. Alzheimer's disease (AD)-related changes.
Section snippets
Vessel disorders
The vessel disorders that are most frequently associated with VaD are atherosclerosis of cerebral arteries (AS), cerebral small vessel disease (SVD), and cerebral amyloid angiopathy (CAA) (Ferrer, 2010, Gorelick et al., 2011, Hachinski et al., 2006, Ince, 2005, Kalaria, 2003, Kalaria and Erkinjuntti, 2006, Roman et al., 1993). These vessel disorders frequently occur in the brains of elderly individuals and become more prevalent and severe with advancing age (Table 1) (Jellinger and Attems, 2010
Types of vascular dementia (VaD) and their relation to vessel disorders and vascular lesions
VaD is the net result of vascular lesions that lead to an impairment of brain function (Ferrer, 2010, Ince, 2005, Roman et al., 1993). Hypoperfusion is thereby, considered to contribute significantly to cognitive decline (Kitamura et al., 2012, Suter et al., 2002). Pure VaD (extensive vascular lesions without widespread AD pathology, i.e., no AD or low degree of AD pathology with Braak NFT stage III or less, CERAD score for neuritic plaque pathology 1 or less, and Aβ phase 2 or less according
Dementia as a result of reduced brain capacity by vascular types of dementia and neurodegeneration
VaD is usually a disease of elderly individuals (Ferrer, 2010, Gorelick et al., 2011, Hachinski et al., 2006, Ince, 2005, Jellinger, 2008, Kalaria and Erkinjuntti, 2006, Roman et al., 1993). In the elderly brain, Alzheimer's disease (AD)-related pathological changes and argyrophilic grain disease (AGD) frequently occur (Braak and Braak, 1997, Braak et al., 2011, Jellinger and Attems, 2012, Thal et al., 2008a, Togo et al., 2002, Tolnay et al., 2001) in addition to CAA, AS, and SVD (Table 1,
Conclusions
This review of the current literature and of our case collection revealed that vascular lesions and vessel disorders are prevalent in most demented elderly individuals often combined with concurrent AD-related lesions (Table 2). The frequent coexistence of AD pathology with SVD and its associated white matter lesions suggests that SVD is a risk factor for AD. As such, it seems to be important for clinical practice to consider the prevalence of AD-related brain lesions in patients with vascular,
Acknowledgments
Dietmar R. Thal received research grants from the Deutsche Forschungsgemeinschaft (DFG: Grant Nos. TH624/4-1,2; TH624/6-1) and the Alzheimer Forschung Initiative (AFI: Grant No. #10810). Johannes Attems is grateful for the support of the Dunhill Medical Trust (R173/1110). Lea Tenenholz Grinberg receives research grants from the National Institute of Health (1R01AG040311-01A1 and 2 P50 AG023501-06), John Douglas French Alzheimer Foundation and Albert Einstein Research Institute —São Paulo.
The
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LTG and JA contributed equally.