JAMDA 16 (2015) 441e443
JAMDA journal homepage: www.jamda.com
Editorial
White Matter Lesions (Leukoaraiosis): A Major Cause of Falls John E. Morley MB, BCh * Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, St. Louis, MO
The concept of vascular lesions in the brain leading to cognitive dysfunction was first shown by Otto Binswagner in 1894.1 Little attention was paid to these asymptomatic vascular lesions until 1986 when both Hachinski2,3 and Awad4,5 separately noted subcortical lesions on brain scans and related these to vascular disease and impaired cognition. Hachinski was the first to use the term leukoaraiosis (“leuko” ¼ white and “araios” ¼ rarefied) indicating that these lesions resulted in reduced x-ray absorption in the white matter. On magnetic resonance imaging using fluid attenuated inversion recovery (FLAIR) the T2-weighted images allow visualization of changes in cerebral white matter, as the cerebrospinal fluid signal is suppressed.6,7 These abnormal regions are called white matter hyperintensities. White matter lesions increase with aging and with cardiovascular risk factors, especially hypertension.8 They are due to the endothelial damage, which results in vessel wall narrowing and tissue ischemia. Damage to the endothelium leads to disruption of the blood brain barrier allowing leakage of toxic substances into the brain (Figure 1). They also have associated lacunar infarcts and large perivascular spaces. These can lead to cerebral microbleeds. The tissue damage leads to oxidative damage to surrounding tissue, which results in release of inflammatory cytokines.9,10 Cytokines stimulate the production of amyloid precursor protein and amyloid-beta, accounting for the common association of Alzheimer disease and vascular dementia.11,12 Tissue damage also results in interruption of connections between the cortex and subcortex. This leads to gray matter atrophy. The combination of damage to the cortex and subcortex leads to cerebral atrophy and an increase in the size of the ventricles.8 There is increasing awareness that mild cognitive impairment (MCI) is a prodromal phase for persons who will go on to develop dementia.13 In 1 study with appropriate treatment, 74% of persons with MCI reversed to normal cognition over a 7.5-year period.14 It would appear that white matter lesions may represent another potentially reversible cause of cognitive dysfunction.15 These lesions in all areas, except the occipital cortex, are associated with a decline in executive function.16 There is some evidence that white matter hyperintensities may be related to poor outcomes from delirium, as well as increasing the propensity for delirium.17 A number of studies have demonstrated, both cross-sectionally and longitudinally, that white matter lesions are strongly related to cognitive decline.18e20 In
* Address correspondence to John E. Morley MB, BCh, Division of Geriatric Medicine, Saint Louis University School of Medicine, 1402 S. Grand Blvd., M238, St. Louis, MO 63104. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.jamda.2015.03.023 1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
particular, they are associated with delayed processing speed and poor attention. These defects then lead to a decline in activities of daily living.21 Because of the early development of leukoaraiosis, it is important to avoid anticholinergic drugs in this population.22e25 These data support the treatment of hypertension to delay progression of cognitive dysfunction. Most data suggest that in older persons a systolic blood pressure of
JAMDA journal homepage: www.jamda.com
Editorial
White Matter Lesions (Leukoaraiosis): A Major Cause of Falls John E. Morley MB, BCh * Divisions of Geriatric Medicine and Endocrinology, Saint Louis University School of Medicine, St. Louis, MO
The concept of vascular lesions in the brain leading to cognitive dysfunction was first shown by Otto Binswagner in 1894.1 Little attention was paid to these asymptomatic vascular lesions until 1986 when both Hachinski2,3 and Awad4,5 separately noted subcortical lesions on brain scans and related these to vascular disease and impaired cognition. Hachinski was the first to use the term leukoaraiosis (“leuko” ¼ white and “araios” ¼ rarefied) indicating that these lesions resulted in reduced x-ray absorption in the white matter. On magnetic resonance imaging using fluid attenuated inversion recovery (FLAIR) the T2-weighted images allow visualization of changes in cerebral white matter, as the cerebrospinal fluid signal is suppressed.6,7 These abnormal regions are called white matter hyperintensities. White matter lesions increase with aging and with cardiovascular risk factors, especially hypertension.8 They are due to the endothelial damage, which results in vessel wall narrowing and tissue ischemia. Damage to the endothelium leads to disruption of the blood brain barrier allowing leakage of toxic substances into the brain (Figure 1). They also have associated lacunar infarcts and large perivascular spaces. These can lead to cerebral microbleeds. The tissue damage leads to oxidative damage to surrounding tissue, which results in release of inflammatory cytokines.9,10 Cytokines stimulate the production of amyloid precursor protein and amyloid-beta, accounting for the common association of Alzheimer disease and vascular dementia.11,12 Tissue damage also results in interruption of connections between the cortex and subcortex. This leads to gray matter atrophy. The combination of damage to the cortex and subcortex leads to cerebral atrophy and an increase in the size of the ventricles.8 There is increasing awareness that mild cognitive impairment (MCI) is a prodromal phase for persons who will go on to develop dementia.13 In 1 study with appropriate treatment, 74% of persons with MCI reversed to normal cognition over a 7.5-year period.14 It would appear that white matter lesions may represent another potentially reversible cause of cognitive dysfunction.15 These lesions in all areas, except the occipital cortex, are associated with a decline in executive function.16 There is some evidence that white matter hyperintensities may be related to poor outcomes from delirium, as well as increasing the propensity for delirium.17 A number of studies have demonstrated, both cross-sectionally and longitudinally, that white matter lesions are strongly related to cognitive decline.18e20 In
* Address correspondence to John E. Morley MB, BCh, Division of Geriatric Medicine, Saint Louis University School of Medicine, 1402 S. Grand Blvd., M238, St. Louis, MO 63104. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.jamda.2015.03.023 1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
particular, they are associated with delayed processing speed and poor attention. These defects then lead to a decline in activities of daily living.21 Because of the early development of leukoaraiosis, it is important to avoid anticholinergic drugs in this population.22e25 These data support the treatment of hypertension to delay progression of cognitive dysfunction. Most data suggest that in older persons a systolic blood pressure of
