Abstract and Introduction
Abstract
Objectives To investigate the relationship between frailty and incident vascular dementia (VaD).
Design Seven-year longitudinal study.
Setting Three-City Study, a French prospective study designed to evaluate the risk of dementia and cognitive decline attributable to vascular risk factors.
Participants Five thousand four hundred eighty community-dwelling persons aged 65 to 95.
Measurements An expert committee established a clinical diagnosis of VaD. Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Participants with prior stroke or prevalent dementia at baseline were excluded from analyses. Multivariate models were used to evaluate the relationship between frailty and incident VaD.
Results At baseline, 6.5% of participants were classified as frail. After 7 years of follow-up, 54 persons were diagnosed with VaD, seven of whom where frail. In the proportional hazards models, frailty was marginally associated with greater risk of all types of dementia and was not associated with incident Alzheimer's disease, but frailty status was independently associated with incident VaD.
Conclusion Frailty is a major risk factor for incident VaD, so its identification could contribute to better estimates of the risk of VaD in elderly adults.
Introduction
The concept of frailty has gained general interest. It is a clinical syndrome characterized by physiological loss of reserves and resilience that puts elderly adults at greater risk of catastrophic decline in health and function. Its most widely used operational definition is that proposed by Fried and colleagues, according to which frailty is defined, i.e., the presence of at least three of the five following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Nonetheless, studying the frailty concept across the large spectrum of population-based studies and its possible relationships with other clinical and biological measures may contribute to a better understanding and definition of this syndrome.
An important role of the central nervous system in manifestations of frailty has been postulated because the central components of frailty, such as problems with gait, balance, and strength, can be related to neurological disturbances. Regarding dementia and cognitive aging in particular, several epidemiological studies have shown that frailty is associated with low cognitive performances. Frailty has also been proposed as a risk factor for cognitive decline, mild cognitive impairment, and Alzheimer's disease (AD). Nonetheless, the relationship between frailty and cognitive impairment has been inconsistently reported and a recent study suggested that poor cognitive performance was a risk factor for dementia rather than frailty per se because the risk was present only in the subgroups of participants presenting with frailty syndrome criteria and poor cognitive performance but not in those only with the frailty phenotype. The association between frailty and the other non-Alzheimer's dementias such as vascular dementia (VaD) has not been studied, yet a wide range of subclinical and clinical cardiovascular abnormalities such as myocardial infarction, low ankle-arm index, and cerebral white matter disease have been associated with the phenotype of frailty, which suggests that frailty could be a clinical manifestation of cardiovascular disease. Chronic inflammation (e.g., atherosclerosis), resulting in a catabolic state, with its systemic manifestation contributing to frailty, partially explains this relationship. Demonstrating an association between frailty and the risk of VaD would be of major importance because it could lead to possible intervention strategies to prevent the development of this type of dementia. Thus, the purpose of this research was to investigate the association between frailty and incident VaD in a large sample of community-dwelling elderly adults from the Three-City Study, a French prospective cohort specifically designed to evaluate the risk of dementia and cognitive decline attributable to vascular risk factors.