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- Macfarlane, M. D., et al.
(författare)
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Shape abnormalities of the caudate nucleus correlate with poorer gait and balance: Results from a subset of the ladis study
- 2015
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Ingår i: The American journal of geriatric psychiatry. - : Elsevier BV. - 1064-7481. ; 23:1, s. 59-U90
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Tidskriftsartikel (refereegranskat)abstract
- Objective Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in frontostriatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter hyperintensities (WMHs) on magnetic resonance imaging has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction. Methods Magnetic resonance imaging scans and clinical gait/balance data (scores from the Short Physical Performance Battery [SPPB]) were sourced from 66 subjects in the previously published LADIS trial, performed in nondisabled individuals older than age 65 years with WMHs at study entry. Data were obtained at study entry and at 3-year follow-up. Caudate nuclei and putamina were manually traced using a previously published method and volumes calculated. The relationships between volume and physical performance on the SPPB were investigated with shape analysis using the spherical harmonic shape description toolkit. Results There was no correlation between the severity of WMHs and striatal volumes. Caudate nuclei volume correlated with performance on the SPPB at baseline but not at follow-up, with subsequent shape analysis showing left caudate changes occurred in areas corresponding to inputs of the dorsolateral prefrontal, premotor, and motor cortex. There was no correlation between putamen volumes and performance on the SPPB. Conclusion Disruption in frontostriatal circuits may play a role in mediating poorer physical performance in individuals with WMHs. Striatal volume and shape changes may be suitable biomarkers for functional changes in this population. © 2015 American Association for Geriatric Psychiatry.
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| 2. |
- Schmidt, R., et al.
(författare)
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White Matter Lesion Progression in LADIS Frequency, Clinical Effects, and Sample Size Calculations
- 2012
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 43:10, s. 2643-2647
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. Methods-Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale. Results-WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm. Conclusions-WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure. (Stroke. 2012; 43:2643-2647.)
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| 3. |
- Benisty, S, et al.
(författare)
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Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study.
- 2009
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:5, s. 478-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. METHODS: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. RESULTS: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (beta = -0.61; p = 0.043), and worse compound scores for speed and motor control (beta = -0.25; p = 0.006), executive functions (beta = -0.19; p = 0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/pallidum and the memory compound Z score (beta = -0.13; p = 0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. CONCLUSION: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH.
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| 4. |
- Jokinen, H., et al.
(författare)
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Diffusion changes predict cognitive and functional outcome: The LADIS study
- 2013
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134. ; 73:5, s. 576-583
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Tidskriftsartikel (refereegranskat)abstract
- Objective A study was undertaken to determine whether diffusion-weighted imaging (DWI) abnormalities in normal-appearing brain tissue (NABT) and in white matter hyperintensities (WMH) predict longitudinal cognitive decline and disability in older individuals independently of the concomitant magnetic resonance imaging (MRI) findings. Methods A total of 340 LADIS (Leukoaraiosis and Disability Study) participants, aged 65 to 84 years, underwent brain MRI including DWI at baseline. Neuropsychological and functional assessments were carried out at study entry and repeated annually over a 3-year observational period. Linear mixed models and Cox regression survival analysis adjusted for demographics, WMH volume, lacunes, and brain atrophy were used to evaluate the independent effect of the DWI measures on change in cognitive performance and functional abilities. Results The mean global apparent diffusion coefficient (ADC) and the relative peak height and peak position of the ADC histogram in NABT predicted faster rate of decline in a composite score for speed and motor control. Higher mean ADC and lower peak height were also related to deterioration in executive functions and memory (specifically working memory), with peak height also being related to more rapid transition to disability and higher rate of mortality. Mean ADC in WMH had less pronounced effects on cognitive and functional outcomes. Interpretation DWI microstructural changes in NABT predict faster decline in psychomotor speed, executive functions, and working memory regardless of conventional MRI findings. Moreover, these changes are related to functional disability and higher mortality. Ann Neurol 2013;73:576–583
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