Post-mortem assessment guidelines for vascular cognitive impairment

New research, led by academics at the University of Bristol, has outlined the first validated set of pathological criteria for assessing the likelihood that cognitive impairment was caused by vascular disease.

07 sept 2016--The term vascular cognitive impairment (VCI) refers to a diverse group of conditions in which memory problems and other impairments of mental function result from inadequate blood flow through the brain. Vascular dementia is a severe form of VCI.
Confirmation of the clinical diagnosis of most diseases that cause dementia depends on post-mortem examination of the brain. The finding of brain tissue damaged by impaired blood supply, or of widespread hardening of the arteries in the brain suggests that the cognitive impairment was caused by vascular disease. However, these pathological abnormalities are also often found in combination with other dementing diseases such as Alzheimer's disease and, until recently, the contribution of different vascular abnormalities to cognitive impairment was difficult to quantify, as there were no validated criteria for determining this.
A large group of UK neuropathologists and other scientists, led by the University of Bristol Dementia Research Group and supported by Alzheimer's Society and Alzheimer's Research UK, has developed a set of Vascular Cognitive Impairment Neuropathology guidelines (VCING) for assessing vascular pathologies in post-mortem brain tissue. The researchers, using brains that had been donated through a scheme called Brains for Dementia Research (BDR), have identified a set of neuropathological determinants that can reproducibly be used to assign a low, intermediate or high likelihood that vascular disease contributed to cognitive impairment in an individual case.
Seth Love, Professor of Neuropathology in the University of Bristol's School of Clinical Sciences, said: "VCING represent a major advance in our ability to assess the contribution of vascular pathology to cognitive impairment and open the way to a range of studies of the determinants of VCI, including of processes that are potentially preventable or modifiable.
"More accurate determination of the contribution of cerebrovascular disease to cognitive impairment and dementia is likely to inform healthcare policy and prioritisation of resources for patients with VCI, and lead to more funding of VCI-related research. It also opens the way to a range of mechanistic studies of pathophysiological determinants of VCI, with a view to identifying processes that are potentially preventable or modifiable."
Dr Rosa Sancho, Head of Research at Alzheimer's Research UK, added: "This collaborative effort has produced a common approach for researchers working to understand the changes that take place in blood vessels that can contribute to cognitive decline. The guidelines developed through this project have the potential to help researchers and clinicians across the globe to streamline their research into dementia, taking a step forward in improving the accuracy and reliability of their work. With a growing international focus on dementia research, it's crucial that researchers are co-ordinated in their approach to studying the condition to ensure we make progress as quickly as possible for the millions affected worldwide."
It is estimated that vascular dementia accounts for around ten to 20 per cent of patients with dementia and it is the second most common cause of dementia after Alzheimer's disease.

More information: Olivia A. Skrobot et al. Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment, Brain (2016).DOI: 10.1093/brain/aww214


Provided by University of Bristol

Physical Activity Linked to Lower Risk of Vascular Dementia But Not AD

Susan Jeffrey
December 21, 2007 — Results of a new prospective study have found an association between increasing levels of physical activity and a lower risk for vascular dementia, but not for Alzheimer's disease (AD). "Our findings show moderate physical activity such as walking and all physical activities combined lowered the risk of vascular dementia in the elderly, independent of several sociodemographic, genetic, and medical factors," first author Giovanni Ravaglia, MD, from University Hospital S. Orsola-Malpighi, in Bologna, Italy, said in a statement from the American Academy of Neurology. "It's important to note that an easy-to-perform moderate activity like walking provided the same cognitive benefits as other more demanding activities."
Unlike some previous reports, they did not find a relationship between increased activity and reduced Alzheimer's disease risk. However, the researchers note they cannot rule out that they may have missed such an association because of a lack of statistical power.
Their findings are published online December 19 in Neurology.
Walking Away from Dementia?
Observational and intervention studies have consistently shown an association between physical exercise and better cognitive performance in selected samples of older adults, although not all studies have confirmed this finding, the authors write.
Longitudinal studies of this link in the elderly are fewer and have had inconsistent results, they note. "A lower risk of all-cause dementia and AD among subjects regularly practicing low- to medium-intensity physical activities was found in some population-based studies but not in others," they write. "Moreover, only a few investigations examined the effect of physical activity on vascular dementia (VaD) risk, and none reported an association."
To look at the effect of physical activity on the risk for AD and VaD, Dr. Ravaglia and colleagues used data from the Conselice Study of Brain Aging (CSBA), a prospective, population-based cohort of 749 Italian subjects aged 65 years and older who were cognitively normal in 1999–2000 after an extensive assessment for clinically overt and preclinical dementia. Baseline physical activity was measured as energy expenditure on activities of different intensities, including walking, stair climbing, moderate activities, vigorous activities, and total physical activity.
During 2003–2004, subjects underwent a follow-up examination looking for overt dementia. Over nearly 4 years of follow-up, there were 86 incident cases of dementia, including 54 cases of AD and 27 of VaD.
The researchers found that, after adjustment for sociodemographic and genetic confounders, the risk for VaD was significantly lower for the upper vs lower tertiles for walking, moderate activity, and total physical activity, associations that persisted after vascular risk factors and overall health status were accounted for.
After similar adjustment for sociodemographic and genetic confounders, the risk for AD was not associated with measures of physical activity, they write. These results did not change after further adjustment for vascular risk factors and overall health and functional status.
"However, because of the width of the CIs for AD found in the CSBA study, it cannot be excluded that significant results for this dementia subtype may have been missed by lack of statistical power," Dr. Ravaglia and colleagues write. "Therefore, we caution the reader against concluding that this study provides definite evidence that AD is not preventable through exercise."
More research on the biologic mechanisms linking physical activity and cognition is needed, they note, but they float a variety of "not mutually exclusive" hypotheses on how cognition may benefit from physical activity. For example, physical activity may improve cerebral blood flow and lower the risk for cerebrovascular disease. Alternatively, activity may stimulate synaptic plasticity, secretion of trophic factors, neurotransmitter synthesis, and neurogenesis to increase cognitive reserve or decrease the secretion of stress hormones such as cortisol that may be toxic.
"Finally, more than from exercise itself, the beneficial effects of physical activity on cognition might result, all or in part, from the mental and social stimulation related to an active lifestyle."
The study was supported by grants from the Italian Ministry of University and Scientific Research (basic-oriented research funds). The authors report no conflicts of interest.
Neurology. Published online December 19, 2007.

Moderate exercise may stall vascular dementia


Older adults who regularly walk for exercise may help lower their risk of vascular dementia, the second-most common form of this disorder after Alzheimer's disease, a study published Wednesday suggests.
In a group of 749 adults who were 65 years of age or older, the Italian researchers found that those who regularly walked or got other forms of moderate exercise were less likely to develop vascular dementia over the next 4 years.
Compared with their sedentary counterparts, active adults had about one quarter the risk of developing vascular dementia. Vascular dementia is caused by an impaired blood flow to the brain. Blockages that narrow the blood vessels supplying the brain or complete blockages that cause a stroke, may also lead to vascular dementia. People with conditions that damage blood vessels throughout the body -- such as high blood pressure or diabetes -- are also at increased risk.
The new findings, published in the online edition of the journal Neurology, build on evidence that lifestyle habits are important in dementia risk. A number of studies have suggested that the same habits that are good for the heart -- such as a healthy diet and regular exercise -- may benefit the aging brain as well.
Although moderate exercise had no effect on Alzheimer's disease, the findings do not mean that exercise has no effect on the risk of Alzheimer's, according to the researchers, led by Dr. Giovanni Ravaglia of the University Hospital S. Orsola-Malpighi in Bologna.
The study included Italian adults with no evidence of mental decline at the outset. The patients were interviewed about their physical activity levels, medical history and any depression symptoms, among other health factors.
Over the next 4 years, 86 study participants were diagnosed with dementia, including 27 with vascular dementia.
Ravaglia's team found that, compared with participants who walked the least often at the study's start, those who logged the most miles were 73-percent less likely to develop vascular dementia.
Similarly, those who got the most moderate exercise of any type -- such as gardening, bicycling and housework -- had a 76 percent lower risk of vascular dementia.
Exercise may benefit mental functioning for a number of reasons, according to the researchers. Aside from improving blood from improving the blood flow to the brain, it may also stimulate the release of key brain chemicals, and enhance the development of new nerve cells or the connections among those cells.
It's also possible, Ravaglia and his colleagues note, that an active lifestyle helps protect the aging brain by keeping older adults mentally stimulated and socially active.
In general, experts advise that all healthy adults try to accumulate at least 30 minutes of moderate exercise on most, if not all, days of the week. Older adults who want to start a new exercise routine should talk with their doctors first.
SOURCE: Neurology, online December 19, 2007.