Impact of Age-Related Cerebral White Matter Changes on the Transition to Disability – The LADIS Study: Rationale, Design and Methodology

Abstract

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65–84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 ± 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Heterogeneity in age-related white matter changes

“…The Leukoaraiosis and Disability (LADIS) Study provides evidence for such differences. The study investigated risk factor profile effects on heterogeneous white matter lesion types and is the only study that systematically compared equally sized groups of individuals with punctate, early confluent, and confluent white matter changes [53]. Individuals with coalescent white matter lesions were significantly older and more frequently had hypertension and a history of stroke as compared to subjects with punctate abnormalities.…”

Cerebral Blood Flow by Using Pulsed Arterial Spin-Labeling in Elderly Subjects with White Matter Hyperintensities

“…8 The current study was approved by both the local and the LADIS study institutional review boards, as well as by the LADIS study steering committee. All subjects gave written informed consent.…”

White Matter Changes Contribute to Corpus Callosum Atrophy in the Elderly: The LADIS Study

“…25 The study involved a total of 11 European centers, either specialized memory clinics or geriatric or neurologic departments with a similar specialization. Briefly, the objective of the LADIS study was to assess the role of ARWMC as an independent predictor of the transition to disability in the initially nondisabled elderly and to describe health-related consequences of ARWMC.…”