Incidence, Manifestations, and Predictors of Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly

Longstreth, W. T.; Arnold, Alice M.; Beauchamp, Norman J.; Manolio, Teri A.; Lefkowitz, David; Jungreis, Charles A.; Hirsch, Calvin H.; O’Leary, Daniel H.; Furberg, Curt D.

doi:10.1161/01.str.0000149625.99732.69

Cited by 438 publications

(407 citation statements)

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“…Longstreth et al (2005), for example, showed that subjects with worsening white matter grade experienced a greater decline on the Digit Symbol Substitution Test (Smith, 1973) than did subjects with no change in white matter grade. The mechanisms underlying this effect are not clear but potentially include disruption of frontal-subcortical circuits (Cummings, 1998;Owen, 2004), cortical atrophy secondary to deinervation, or concomitant microvascular changes in the cortex.…”

Section: Discussionmentioning

confidence: 99%

“…Cortical and frontal lobe atrophy have also been shown to correlate with global cognition and measures of executive functioning (Raz, Williamson, Gunning-Dixon, Head, & Acker, 2000). A significant association has been established between white matter signal hyperintensities and cognition in several studies (Baum, Schulte, Girke, Reischies, & Felix, 1996;Breteler et al, 1994;Cook et al, 2004;DeCarli et al, 2005;De Groot et al, 2002;Fukui, Sugita, Sato, Takeuchi, & Tsukagoshi, 1994;Kovari et al, 2004;Kramer, Reed, Mungas, Weiner, & Chui, 2002;Longstreth et al, 2005;Matsubayashi, Shimada, Kawamoto, & Ozawa, 1992;Ylikoski et al, 2000) but not in others (Boone et al, 1992;Burns et al, 2005;Fein et al, 2000;Wahlund, Almkvist, Basun, & Julin, 1996). Similarly, the role of lacunae in cognition has not been well defined, with some studies showing a negative relationship between lacunae and cognition (Gold et al, 2005;Kramer et al, 2002;Longstreth et al, 2005;Price et al, 1997), whereas others have not, particularly when accounting for the presence of other important pathological markers, such as white matter disease (Fein et al, 2000;Mungas et al, 2001).…”

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Longitudinal MRI and cognitive change in healthy elderly.

et al. 2007

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Cross-sectional studies of normal aging indicate an association between memory and hippocampal volume, and between executive functioning and subcortical-frontal circuits. Much less is known, however, about the relationship between longitudinal MRI changes and cognitive decline. The authors hypothesized that longitudinal change in memory would be best predicted by change in hippocampal volumes, whereas change in executive functioning would be best predicted by cortical atrophy and progression of MRI markers of cerebrovascular disease. For this study, 50 healthy elderly subjects underwent structural MRI and cognitive testing at baseline and again at follow-up, with a mean follow-up interval of 45 months. Volumetric MRI measures were hippocampus, cortical gray matter, white matter signal hyperintensity (WMSH), and lacunae. Neuropsychological measures were psychometrically robust composite scores of episodic memory (MEM) and executive functioning (EXEC). Hierarchical multiple regression indicated that a decrease in hippocampus was associated with a decline in MEM, whereas decreased cortical gray matter and increased WMSH were independently associated with a decline in EXEC. Results suggest that in normal aging, cognitive functioning declines as cortical gray matter and hippocampus decrease, and WMSH increases. The association between WMSH and EXEC further highlights the cognitive sequealae associated with cerebrovascular disease in normal elderly.Correspondence concerning this article should be addressed to Joel H. Kramer , 1997). There are also age-related increases in subcortical ischemic vascular disease that can independently contribute to cognitive decline and dementia (Román, Erkinjuntti, Wallin, Pantoni, & Chui, 2002). Population-based studies have reported "silent" (i.e., asymptomatic) lacunae in 11%-28% of clinically asymptomatic elderly (Longstreth et al., 1998;Price et al., 1997;Vermeer et al., 2003), whereas the prevalence of white matter signal hyperintensities on MRI has ranged from 30% to 100% across studies of healthy elderly samples (Breteler et al., 1994;Longstreth et al., 1998;Ylikoski et al., 2000). Diffusion tensor MRIs have shown a progressive reduction in fractional anisotropy and an increase in diffusivity with age (Charlton et al., 2006).Despite the co-occurrence of age-related cognitive decline and brain changes, associations between brain volume and cognitive ability in healthy subjects have been difficult to establish. Although several studies have reported that hippocampal atrophy is associated with poorer episodic memory performance in older subjects (De Leon et al., 1997;Golomb et al., 1996), an extensive review and meta-analysis by Van Petten (2004) noted considerable variability across studies. The common correlation between hippocampal volume and memory performance across 33 studies was statistically significant but quite low, leading to the conclusion that the evidence for a positive relationship between hippocampal volume and memory performance was weak. Divergent result...

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Section: Discussionmentioning

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Longitudinal MRI and cognitive change in healthy elderly.

et al. 2007

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“…31 We have shown that progression of PV WMH volume is associated with increased gait slowing over time. The relationship between increased rate of WMH burden and worse performance on gait testing over time has been reported, 15,32 although previous studies did not examine the potential differential relationships between subcortical and PV WMH volume change and progressive gait dysfunction. Increased progression of subcortical WMH lesions was associated with increased rate of memory decline, independent of cerebral or hippocampal atrophy.…”

Section: Figurementioning

confidence: 99%

Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline

Silbert¹,

Nelson²,

Howieson³

et al. 2008

Neurology

227

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“…In the Austrian Stroke Prevention Study, WMH levels increased steadily over 6 years, and while cognition was stable at 3 years (Schmidt et al 1999), it was significantly impaired after 6 years (Schmidt et al 2005; also see Prins et al 2005). The longitudinal increase of WMH can negatively affect several cognitive domains (Longstreth et al 2005), including executive function, with an increase of subcortical WMH ) and mental processing speed, when accompanied by an increase in periventricular WMH (van den Heuvel et al 2006). A high baseline level of WMH in deep and periventricular WM was most predictive of a longitudinal progression of WMH in the elderly (Sachdev et al 2007).…”

Section: Longitudinal Imaging Studies In Humansmentioning

confidence: 99%

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

Kohama

Rosene

Sherman

2011

AGE

121

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The cognitive decline associated with normal aging was long believed to be due primarily to decreased synaptic density and neuron loss. Recent studies in both humans and non-human primates have challenged this idea, pointing instead to disturbances in white matter (WM) including myelin damage. Here, we review both cross-sectional and longitudinal studies in humans and non-human primates that collectively support the hypothesis that WM disturbances increase with age starting at middle age in humans, that these disturbances contribute to age-related cognitive decline, and that age-related WM changes may occur as a result of free radical damage, degenerative changes in cells in the oligodendrocyte lineage, and changes in microenvironments within WM.

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Incidence, Manifestations, and Predictors of Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly

Abstract: Background and Purpose-Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging. Methods-The

Cited by 438 publications

References 17 publications

Longitudinal MRI and cognitive change in healthy elderly.

Longitudinal MRI and cognitive change in healthy elderly.

Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

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