Memory after silent stroke Hippocampus and infarcts both matter

Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, NY, USA.
Neurology (Impact Factor: 8.29). 01/2012; 78(1):38-46. DOI: 10.1212/WNL.0b013e31823ed0cc
Source: PubMed


Memory decline commonly occurs among elderly individuals. This observation is often attributed to early neurodegenerative changes in the hippocampus and related brain regions. However, the contribution of vascular lesions, such as brain infarcts, to hippocampal integrity and age-associated memory decline remains unclear.
We studied 658 elderly participants without dementia from a prospective, community-based study on aging and dementia who received high-resolution structural MRI. Cortical and subcortical infarcts were identified, and hippocampal and relative brain volumes were calculated following standard protocols. Summary scores reflecting performance on tasks of memory, language, processing speed, and visuospatial function were derived from a comprehensive neuropsychological battery. We used multiple regression analyses to relate cortical and subcortical infarcts, hippocampal and relative brain volume, to measures of cognitive performance in domains of memory, language, processing speed, and visuospatial ability.
Presence of brain infarcts was associated with a smaller hippocampus. Smaller hippocampus volume was associated with poorer memory specifically. Brain infarcts were associated with poorer memory and cognitive performance in all other domains, which was independent of hippocampus volume.
Both hippocampal volume and brain infarcts independently contribute to memory performance in elderly individuals without dementia. Given that age-associated neurodegenerative conditions, such as Alzheimer disease, are defined primarily by impairment in memory, these findings have clinical implications for prevention and for identification of pathogenic factors associated with disease symptomatology.

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    • "Symptoms of silent stroke, therefore, may go unreported in spite of lasting tissue damage. Considering the particular vulnerability of regions of the HPC to ischemic events (Johansen et al., 1987; Schmidt-Kastner and Freund, 1991; Hsu and Buzsáki, 1993), the association of smaller hippocampi and memory decline in silent stroke (Blum et al., 2012), the HPC represents a clinically relevant target for pre-clinical studies in silent stroke. Intracerebral infusion of ET-1 may represent a particularly suitable method due to its properties to reduce local blood flow and produce ischemic lesions in a dose-dependent manner (Yanagisawa et al., 1988). "
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    ABSTRACT: Silent focal ischemic mini infarcts in the brain are thought to cause no clinically overt symptoms. Some populations of hippocampal cells are particularly sensitive to ischemic events, however, rendering hippocampal functions especially vulnerable to ischemia-induced deficits. The present study investigated whether an otherwise silent ischemic mini infarct in the hippocampus (HPC) can produce impairments in spatial performance in rats. Spatial performance was assessed in the ziggurat task (ZT) using a 10-trial spatial learning protocol for 4 days prior to undergoing hippocampal ischemic lesion or sham surgery. Hippocampal silent ischemia was induced by infusion of endothelin-1 (ET-1), a potent vasoconstrictor, into either the dorsal or the ventral hippocampus (dHPC and vHPC). When tested postoperatively in the ZT using a standard testing protocol for 8 days, rats with hippocampal lesions exhibited no spatial deficit. Although spatial learning and memory in the ZT were not affected by the ET-1-induced silent ischemia, rats with dHPC stroke showed more returns when navigating the ZT as opposed to the vHPC rats. Comparison of region-specific HPC lesions in the present study indicated that dorsal hippocampal function is critically required for topographic orientation in a complex environment. Topographic disorientation as reflected by enhanced return behaviors may represent one of the earliest predictors of cognitive decline after silent ischemic insult that may be potentially traced with sensitive clinical examination in humans.
    Frontiers in Behavioral Neuroscience 08/2014; 8:261. DOI:10.3389/fnbeh.2014.00261 · 3.27 Impact Factor
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    • "Cognitive impairments are among the better characterized sequelae following brain ischemia, with memory being the most affected domain, followed by attention and executive function (Zola-Morgan et al. 1986; Kartsounis et al. 1995; Moulaert et al. 2010; Mateen et al. 2011). Post mortem studies have suggested that hippocampal damage may be a key factor associated with cognitive impairment after ischemic events (Zola-Morgan et al. 1986; Bachevalier and Meunier 1996; Blum et al. 2012). Despite intense efforts, few pharmacological treatments have effectively minimized the functional impairments following cerebral ischemia (Auriel and Bornstein 2010). "
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    ABSTRACT: The present study investigated whether cannabidiol (CBD), a major non-psychoactive constituent of marijuana, protects against hippocampal neurodegeneration and cognitive deficits induced by brain ischemia in adult mice. Male Swiss mice were subjected to a 17 min of bilateral common carotid artery occlusion (BCCAO) and tested in the Morris water maze 7 days later. CBD (3, 10, and 30 mg/kg) was administered 30 min before and 3, 24, and 48 h after BCCAO. After behavioral testing, the brains were removed and processed to evaluate hippocampal cell survival and degeneration using Nissl staining and FluoroJade C histochemistry, respectively. Astroglial response was examined using immunohistochemistry for glial fibrillary acidic protein (GFAP). CBD (3-30 mg/kg) improved spatial learning performance in BCCAO mice. The Nissl and FJC staining results showed a decrease in hippocampal neurodegeneration after CBD (10 and 30 mg/kg) treatment. GFAP immunoreactivity was also decreased in ischemic mice treated with CBD (30 mg/kg). These findings suggest a protective effect of CBD on neuronal death induced by ischemia and indicate that CBD might exert beneficial therapeutic effects in brain ischemia. The mechanisms that underlie the neuroprotective effects of CBD in BCCAO mice might involve the inhibition of reactive astrogliosis.
    Neurotoxicity Research 02/2014; 26(4). DOI:10.1007/s12640-014-9457-0 · 3.54 Impact Factor
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    • "Medical Research Council Cognitive Function and Aging Study, 2001). These covert strokes are not clinically silent as was earlier thought, but are associated with cognitive deficits, particularly executive dysfunction (Werring et al., 2004; Prins et al., 2005), and memory loss (Blum et al., 2012). Covert strokes and white matter lesions each more than double the risk of stroke and the risk of dementia (Vermeer et al., 2003a,b; Debette and Markus, 2010). "
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    ABSTRACT: Demographic changes and improvements in health care are projected to result in dramatic increases in the prevalence of dementia. Alzheimer's disease is widely considered to be the primary cause of dementia - a disease for which there is currently no cure nor effective treatment, and for which it is thought that little can be done to mitigate risk. However, an increasing understanding of the role and extent of vascular contributions to the development of dementia, and appreciation of the interactions between stroke and Alzheimer's disease, suggest that targeting vascular risk factors may be very beneficial in reducing the impact of dementia. We also describe how active stimulation of the brain throughout the life course builds cognitive reserve that can offset or compensate for cognitive decline in later life. Finally, we discuss the implications of these emerging approaches for dementia prevention and advocate for the urgent implementation of more extensive public health strategies to improve vascular health.
    Frontiers in Neurology 03/2013; 4:13. DOI:10.3389/fneur.2013.00013
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