Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort

The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly.     

Brain atrophy and white matter hyperintensities in early Parkinson's disease

The purpose of this research was to examine the extent of global brain atrophy and white matter hyperintensities (WMH) in early Parkinson's disease (PD) compared to normal controls (NC), to explore the relationship between the MRI variables and cognition in PD. In this multicenter study we included 155 PD patients (age 65.6 ± 9.1 years, disease duration 26.7 ± 19.9 months) and 101 age‐matched NC. On 3D‐T1‐WI, we calculated normalized brain volumes using SIENAX software. WMH volumes were assessed semiautomatically. In PD patients, correlation and regression analyses investigated the association between atrophy and WMH outcomes and global, attention‐executive, visuospatial, and memory cognitive functions. Regression analysis was controlled for age, education, depression score, motor severity, cerebrovascular risk, and sex. No significant MRI variable volume group differences were found. The models did not retain any of the imaging variables as significant predictors of cognitive impairment. There was no evidence of brain atrophy or higher WMH volume in PD compared to NC, and MRI volumetric measurements were not significant predictors of cognitive functions in PD patients. We conclude that global structural brain changes are not a major feature in patients with incident PD. © 2009 Movement Disorder Society     

Corpus callosum atrophy,white matter lesions,and frontal executive dysfunction in normal aging and Alzheimer's disease. A community-based study: the Tajiri Project

BACKGROUND AND OBJECTIVES: Cerebral MRIs of normal aging and Alzheimer's disease (AD) frequently reveal corpus callosum (CC) atrophy, white matter hyperintensity (WMH), and hippocampal atrophy. However, their relationship or the relationship between these findings and cognitive function has not been fully studied. We investigated the relationship between CC atrophy, WMH, and hippocampal atrophy, together with frontal executive dysfunction in both normal aging and AD. METHOD: We examined 170 randomly selected residents from a designated community: 99 Clinical Dementia Rating (CDR) 0 (healthy, control group, HC) participants, 54 CDR 0.5 (very mild AD) patients, and 17 CDR 1 & 2 (probable AD) patients. By means of MRI, WMH and CC atrophy were visually rated. Four portions of the CC and the hippocampal width were measured. A Mini-Mental State Examination and Cognitive Abilities Screening Instrument (CASI) were performed to assess global function. For the frontal function, the CASI subitems of attention and word fluency, letter-based fluency, the Digit Symbol test of the WAIS-R, and Trail Making Tests were performed. RESULTS: Those patients with CDR 1 & 2 had both hippocampal and CC atrophy, whereas the CDR 0.5 patients had only hippocampal atrophy. Frontal executive dysfunction was associated with CC atrophy in both the HC and AD groups. Significant Spearman correlations were noted between CC atrophy and WMH in both groups. The combined effect of CC atrophy and WMH was noted only in the verbal fluency test in the HC group. CONCLUSION: In both groups, CC atrophy was associated with frontal executive dysfunction. The combined effect of CC atrophy and WMH in normal aging was probably due to subclinical ischemic conditions.     

Increased brachial-ankle pulse wave velocity is independently associated with white matter hyperintensities

Background: White matter hyperintensities (WMHs) are a risk factor for stroke. Their etiology is considered to be cerebral microvascular abnormality. However, the association between WMHs and arteriosclerosis is not yet clear. The aim of this hospital-based cohort study was to identify the arteriosclerotic characteristics associated with WMHs. Methods: We cross-sectionally included 240 consecutive patients with no history of stroke. We measured the brachial-ankle pulse wave velocity (baPWV), ankle brachial pressure index, and intima-media thickness of the common carotid artery, and we performed magnetic resonance brain imaging. WMHs were defined as periventricular hyperintensity (Fazekas grade ≥3) and/or separate deep white matter hyperintense signals (Fazekas grade ≥2). We determined the prevalence of WMHs, silent brain infarction (SBI), hypertension, hypercholesterolemia, diabetes mellitus, ischemic heart disease, and smoking. We compared 2 groups of patients, defined by the presence or absence of WMHs, using multiple logistic regression analyses. Results: In multivariable analysis, SBI (OR 3.38; 95% CI 1.52-7.72), hypertension (OR 2.23; 95% CI 1.03-5.15), female sex (OR 1.95; 95% CI 1.03-3.76), baPWV (OR 1.12; 95% CI 1.02-1.23), and age (OR 1.09; 95% CI 1.04-1.14) were independently associated with WMHs. Conclusions: An increased baPWV is associated with WMHs. Management of increased baPWV may help to prevent the progression of WMHs and stroke.     

Associations of microalbuminuria with brain atrophy and white matter hyperintensities in hypertensive sibships

BACKGROUND: Because of similarities between brain and kidney microvascular disease, there may be a relationship between measures of renal microvascular disease and brain structural changes in middle aged or elderly individuals. OBJECTIVE: To determine whether the urine albumin/creatinine ratio (UACR), a measure of renal microvascular disease, is associated with brain atrophy and white matter hyperintensities. METHODS: As part of a larger study of the genetics of hypertension, we performed brain imaging and assessed microalbuminuria and other vascular risk factors including diabetes, hypertension, hyperlipidemia and hyperhomocysteinemia in 1253 individuals from hypertensive sibships (age mean 63.8 years, range 50 to 91; 65% women; 49% African-American; 78% hypertensive). Semi-automated quantitative measurements of brain atrophy (BA) ventricular volume, and white matter hyperintensities (WMH) were carried out on the brain MR scans. RESULTS: In logistic regression models, elevated UACR was associated with greater BA (odds ratio (OR)=1.70 (95% CI 1.14, 2.54) and burden of WMH (OR=2.06 (95% CI 1.37, 3.10) after controlling for demographic factors, blood glucose, hypertension severity, duration of smoking and serum homocysteine. In contrast to elevated UACR, the associations with elevated creatinine or reduced glomerular filtration rate and WMH were not significant in the fully adjusted models. CONCLUSIONS: In this cohort with an overrepresentation of hypertensives, elevated UACR was independently associated with both brain atrophy and white matter hyperintensities. Brain volume loss and WMH burden might represent expressions of microvascular disease that share common mechanisms with nephrosclerosis.     

Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study

Background White matter hyperintensities (WMH) on MRI are associated with disorders of gait and balance and with cognitive impairment. The most suitable method to assess WMH in relation to the clinical evaluation of disturbances in these areas has not yet been established. Aim To compare a simple visual rating scale, a detailed visual rating scale and volumetric assessment of WMH with respect to their associations with clinical measures of physical performance and cognition. Methods Data were drawn from the multicentre, multinational LADIS study. Data of 574 subjects were available. MRI analysis included assessment of WMH using the simple Fazekas scale, the more complex Scheltens scale and a semi-automated volumetric method. Disturbances of gait and balance and general cognitive function were assessed using the Short Physical Performance Battery (SPPB) and the Mini Mental State Examination (MMSE), respectively. Results Irrespective of the method of measuring WMH, subjects with disturbances of gait and balance (SPPB≤10) had more WMH than subjects with normal physical performance. Subjects with mild cognitive deficits (MMSE≤25) had more WMH than subjects with normal cognition. Correlations between clinical measures and WMH were equal across methods of WMH measurement (SPPB: Spearman r=−0.22, −0.25, −0.26, all p<0.001; MMSE: Spearman r=−0.11, −0.10, −0.09, all p<0.05, for Fazekas scale, Scheltens scale and volumetry, respectively). These associations remained significant and comparable after correcting for age, gender and education in multivariate linear regression analyses. Conclusion Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition. This suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting. R. Schmidt: on behalf of the LADIS study group Received in revised form: 25 November 2005     

Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD

The authors investigated the interaction between medial temporal lobe (MTL) atrophy and white matter hyperintensities (WMH) in Alzheimer disease (AD). They measured the MTL and WMH on MRI in 58 AD patients and 28 controls. MTL atrophy was associated with an increased risk of AD (OR = 6.2), but there was no significant association between WMH and AD. Moreover, there was an interaction between MTL and WMH (p = 0.045). These results suggest that vascular and Alzheimer-type pathology act in synergy in the clinical syndrome of AD.     

Memory and executive function in older adults: relationships with temporal and prefrontal gray matter volumes and white matter hyperintensities

Forty-eight healthy adults aged 65-85 were recruited for structural magnetic resonance scans after an extensive neuropsychological battery that ensured a high degree of variability across the sample in performance on long-term memory tests, and on tests traditionally thought to rely on prefrontal cortex. Gray matter volumes were measured for three gyri in the frontal lobe (superior, middle, inferior), six gyri in the temporal lobe (superior, middle, inferior, fusiform, parahippocampal, and hippocampus), and the occipital lobe. Gray matter volumes declined across the age range evaluated, but with substantial regional variation--greatest in the inferior frontal, superior temporal, and middle temporal gyri but negligible in the occipital lobe. Both memory performance and executive function declined as the number of hyperintense regions in the subcortical white matter increased. Memory performance was also significantly correlated with gray matter volumes of the middle frontal gyrus (MFG), and several regions of temporal neocortex. However, the correlations were all in the negative direction; better memory performance was associated with smaller volumes. Several previous reports of significant negative correlations between gray matter volumes and memory performance are described, so that the possible reasons for this surprising finding are discussed.     

White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease

BACKGROUND AND OBJECTIVE: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and examined the association between WMH and structural and cognitive variables. METHODS: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates. RESULTS: Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R(2) = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks. CONCLUSION: Objective measurements of tissue volumes in AD demonstrated that WMH are significantly related to cortical atrophy and neuropsychological impairment.     

Increased frontal white matter diffusion is associated with glial metabolites and psychomotor slowing in HIV

Diffusion-weighted imaging (DWI) measures brain water diffusion that is sensitive to microscopic brain injury. A total of 11 HIV seropositive patients were compared to 14 seronegative subjects using DWI, proton magnetic resonance spectroscopy (1H MRS), and neuropsychological tests. The apparent diffusion coefficient (ADC) was significantly increased in the HIV patients, primarily in the frontal white matter (FWM; +5%, p=0.01). Diffusivity correlated positively with the glial marker myo-inositol (r=0.5, p=0.008) and negatively with cognitive performance (NPZ-8 composite score; r=-0.43, p=0.05). These findings suggest increased brain water diffusion may reflect increased glial activation or inflammation, which in turn, may contribute to the cognitive deficits in HIV patients.     

Subclinical white matter lesions and medial temporal lobe atrophy are associated with EEG slowing in a memory clinic cohort

Objective

The aim of the study was to describe the relationship between electroencephalographic (EEG) findings obtained by standardized visual analysis, subclinical white matter lesions (WML) and brain atrophy in a large memory clinic population.

Late onset bipolar disorder associated with white matter hyperintensities: a pathophysiological hypothesis

Vascular depression is, nowadays, a well-established concept in the literature. However, the possible emergence of late onset bipolar disorder in subjects with no antecedents of mood disorder or after a chronic or recurrent course of unipolar depression constitutes a poorly studied issue, despite its importance in clinical practice. Here, we present the case of a 72-year-old female patient who began to present recurrent major depressive symptoms, resistant to pharmacological treatment, from the age of 58. Three years later, she started to present phases of mania with rapid cycling features. A brain MRI scan showed prominent white matter hyperintensities (WMH). WMH are frequently found in the elderly population, but with greater burden in individuals with hypertension and cerebrovascular disease. WMH impair cortical function and damage the cerebral tissue. WMH have been associated with adult-onset bipolar disorder and late onset depression, and are linked to a worse prognosis of both conditions. The present case report highlights the possibility that vascular-related WMH may provoke late onset bipolar disorder by damaging frontolimbic circuits implicated in the pathophysiology of mania.     

Cerebral white matter changes are associated with abnormalities on neurological examination in non-disabled elderly: the LADIS study

Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a 3-year period and their possible associations with WMC in a cohort of initially non-disabled elderly subjects. Data from the multicenter Leukoaraiosis And DISability study were used. A standard neurological examination was performed at baseline and at each of the annual follow-up visits. A standard MRI scan was performed at baseline and after 3-years. WMC severity was graded as mild, moderate, or severe on the Fazekas scale, while the Rotterdam scale was used to assess progression. Infarcts and their occurrence were also assessed. Six hundred and thirty-nine non-disabled subjects were enrolled (mean age 74.1 ± 5.0, M/F: 288/351). Severe WMC at baseline were associated with gait and stance abnormalities, upper motor signs, and fingertap slowing. This effect was independent of age, sex, lacunar and non-lacunar infarcts. The occurrence of stance abnormalities, upper motor signs, primitive reflexes and fingertap slowing during the 3-year follow-up period was associated with both baseline WMC load and their progression. The occurrence of the same abnormalities plus extrapyramidal and primitive reflexes was associated with incident lacunar infarcts. In our cohort of non-disabled elders, severe WMC were associated with the presence and the occurrence of neurological signs, independently of other vascular brain lesions, confirming that these lesions have clinical relevance.