White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy

This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5‐T MRI. CSF Aβ₄₂ and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ₄₂ and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

White matter hyperintensities in patients with multiple system atrophy

IntroductionAlthough white matter hyperintensities (WMHs) are prevalent in the elderly, the clinical significance and the underlying pathophysiological mechanisms of WMHs in neurodegenerative disorders have not been fully clarified.ObjectiveThe present study aimed to determine the degree of WMHs in patients with multiple system atrophy (MSA), and analyze the predisposing factors for WMHs.MethodsTwo raters blinded to clinical information assessed cerebrovascular lesions in brain MRIs from patients with MSA and age-matched controls. Patients with Parkinson’s disease (PD) were similarly studied as a disease control. The results obtained were compared with the clinical characteristics of the patients and statistically analyzed.ResultsWMHs in patients with MSA were statistically greater compared with PD patients or controls. There were no significant differences in either lacunar or territorial infarcts. Multiple linear regression analysis demonstrated that age, supine systolic blood pressure, and a drop in orthostatic blood pressure were significantly and independently correlated with WMH scores in MSA.ConclusionsThe present study suggests that white matter is differentially involved in MSA. In addition to aging, cerebral hypoperfusions caused by fluctuations of blood pressure may be a significant contributing factor to WMHs in MSA, although the possibility that degenerative processes occurring in oligodendrocytes may be associated with WMHs should not be excluded.     

White matter hyperintensities in patients with multiple system atrophy

Recent studies have reported that the majority of patients with multiple system atrophy (MSA) had hypertensive heart disease. However, the effect of autonomic failure on the brain in MSA has not been studied. We consecutively enrolled 63 patients with MSA and selected 63 age- and sex-matched healthy subjects. We performed a comparative analysis of cerebrovascular lesions between the patients with MSA and the control subjects and analyzed predisposing factors for cerebrovascular lesions in the patients with MSA. There was no significant difference in lacune and territorial infarcts between the patients with MSA and the control subjects. The median grading score of white matter hyperintensity (WMH) was significantly higher in the patients with MSA (1.0, interquartile range 0.5–2.0) than the control subjects (0.0, interquartile range 0.0–1.0; P < 0.01). In the patients with MSA, there was strong correlation between the grading score of WMH and supine systolic blood pressure (r = 0.529, P < 0.001) after adjusting for age. Multiple linear regression analysis showed that age and supine systolic blood pressure was significantly and independently correlated with the grading score of WMH. The present study demonstrates that patients with MSA had more severe WMH and that supine systolic pressure is a major contributing factor for the severity of WMH, suggesting that patients with MSA have target-organ damage of the brain.     

White matter lesions and hippocampal atrophy in Alzheimer's disease

White matter lesions (WML) and hippocampal atrophy (HA) on MRI commonly co-occur in Alzheimer's disease (AD) and are thought to play a role in the etiology of AD. It is still not known whether WML and HA are independent or related. The authors investigated the relation between WML and HA in 179 patients with probable AD who had a cerebral MRI. A linear relation was found between WML and HA, especially for WML in the frontal and parieto-occipital regions. The results suggest that vascular pathology and typical AD pathology (HA) are related.     

Behavioural and psychological symptoms are not related to white matter hyperintensities and medial temporal lobe atrophy in Alzheimer's disease

BACKGROUND: The neuropathology of behavioural and psychological symptoms is much less understood than the neuropathology of cognitive impairment in AD. On MRI, medial temporal lobe atrophy (MTA) is presumed to reflect Alzheimer- type pathology. White matter hyperintensities (WMH) are considered markers of vascular pathology. AIM: We investigated differences in prevalence of behavioural and psychological symptoms in AD according to the presence of MTA and WMH on MRI. METHODS: Behavioural and psychological symptoms of 111 consecutive AD patients were assessed using the Neuropsychatric Inventory (NPI). Symptoms were considered present when the score was > or =1. On MRI, MTA was rated using the five-point Scheltens-scale and WMH using the four-point Fazekas-scale. Both MRI measures were dichotomised (MTA: absent 0/1, present 2-4; WMH absent 0/1, present 2/3). RESULTS: Of the 111 AD patients, 60(55%) had MTA, and 32(29%) had WMH. The presence of MTA was associated with the presence of WMH (chi (2) = 11.8, p < 0.001). The prevalence of behavioural and psychological symptoms--defined as a NPI score of > or =1 on at least one symptom--was 74%.The median NPI score of the total study population was 6(0-41). There was no difference in prevalence according to MTA (p = 0.53) or WMH (p = 0.18). On inspection of individual NPI items, neither MTA, nor WMH was related to any of the symptoms. CONCLUSIONS: There were no differences in prevalence of behavioural and psychological symptoms according to MTA or WMH, as rated on MRI. This suggests that the occurrence of those symptoms depends on other determinants, such as coping style or genetic make-up.     

White matter hyperintensities and cortical acetylcholinesterase activity in parkinsonian dementia

OBJECTIVE: To investigate the relationship between the severity of white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity in parkinsonian dementia (PDem). METHODS: PDem (n = 11) and control subjects (n = 14) underwent [11C]methyl-4-piperidinyl propionate (11C-PMP) AChE brain positron emission tomography and magnetic resonance (MR) imaging. Presence of WMH on proton density and T2 MR images was scored using a modified version of the semi-quantitative rating scale by Scheltens et al. [J Neurol Sci114 (1993)]. RESULTS: Analysis demonstrated significantly lower mean cortical (11)C-PMP k3 hydrolysis rates in PDem (-19.9%) when compared with control subjects (P < 0.0001). PDem subjects had higher mean severity of WMH (+20.1%) when compared with control subjects (P < 0.05). When WMH severity was entered into the analysis of variance model, there was no significant co-variate effect on cortical AChE activity (F = 0.24, ns). CONCLUSIONS: The concomitant presence of mild to moderate WMH in patients with PDem does not have a significant effect on cortical AChE activity.     

White matter changes associated with psychotic symptoms in Alzheimer's disease patients

This study explored the relationship between white matter changes seen on magnetic resonance imaging (MRI) and neuropsychiatric symptoms of Alzheimer's disease patients. Fifty-five probable Alzheimer's disease patients were assessed with Behavioral Rating Scale for Dementia (BRSD) and MRI. White matter changes in the bilateral frontal or parieto-occipital region and left basal ganglia significantly corresponded with the score of the Psychotic Symptoms subscale of BRSD. Secondary analyses revealed that white matter changes were not associated with paranoid delusion and hallucination, but only with delusional misidentification. Our results suggest that white matter changes in Alzheimer's disease patients probably contribute to the development of specific psychotic symptoms, namely delusional misidentification.     

Linking cortical atrophy to white matter hyperintensities of presumed vascular origin

We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tractography was used to define WMH connectivity to cortical regions. Linear mixed-effects models were applied to analyze the relationship between cortical thickness and connectivity to WMH. Factors associated with cortical thickness (age, sex, hemisphere, region, individual differences in cortical thickness) were added as covariates. Median age was 64 [IQR 46–76] years. Visual inspection of surface maps revealed distinct connectivity patterns of cortical regions to WMH. WMH connectivity to the cortex was associated with reduced cortical thickness (p = 0.009) after controlling for covariates. This association was found for periventricular WMH (p = 0.001) only. Our results indicate an association between WMH and cortical thickness via connecting fiber tracts. The results imply a mechanism of secondary neurodegeneration in cortical regions distant, yet connected to subcortical vascular lesions, which appears to be driven by periventricular WMH.     

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     

White matter magnetic resonance imaging hyperintensity in Alzheimer's disease: correlations with corpus callosum atrophy

We have previously demonstrated with MRI that as well as marked white matter involvement in late-onset Alzheimer's disease (AD), atrophy of the corpus callosum may also be present. This finding prompted us to study possible correlations between atrophy of the corpus callosum and white matter hyperintensity (WMH) and between white matter lesions and the severity of the disease. We compared the corpus callosum and white matter lesions on MRI from 15 AD patients and 15 controls. The white matter lesions were scored according to the Scheltens' rating scale. We found a significant reduction of the area of the corpus callosum and more severe white matter lesions in AD patients than in controls. Both atrophy of the corpus callosum and the severity of lesions depended mainly on the diagnosis of senile dementia of the Alzheimer type and on age but not on the diagnosis of presenile AD. We demonstrated a negative correlation between white matter lesions scores and areas of corpus callosum in AD patients and no correlation between the white matter lesions and the severity of the disease. We demonstrated that white matter lesions including WMH and atrophy of the corpus callosum are more frequent in AD than in controls. The predominance of white matter lesions in senile AD may be explained by the combination of aging and disease processes.     

White matter hyperintensities in subjects with bipolar disorder

There have been divergent reports on the prevalence and severity of white matter hyperintensities (WMH) on brain magnetic resonance (MR) images in subjects with bipolar disorder. In the present study, evaluations were made on the prevalence and severity of WMH in subjects with bipolar disorder using contiguous 3-mm thick MR slices as well as fluid attenuated inversion recovery (FLAIR) images. A detailed WMH rating system was employed to assess these WMH. A total of 43 bipolar patients, as diagnosed by the Structured Clinical Interview from the Diagnostic and Statistical Manual-IV (SCID-IV), and 39 healthy comparison subjects were scanned using a 1.5-T whole body GE magnetic resonance scanner. WMH were assessed with a modified composite version of the Fazekas' and Coffey's rating scales to detect less severe WMH. Periventricular and subcortical WMH were coded separately. Subjects with bipolar disorder had greater prevalence of WMH abnormalities than comparison subjects (Bipolar, grade 1 = 11.6%, grade 2 = 9.3%, grade 3 = 7.0%; Comparison, grade 1 = 5.1%, grade 2 = 2.6%, grade 3 = 0%). This difference is mainly due to the differences in deep WMH (Bipolar, grade 1 = 14.0%, grade 2 = 14.0%; Comparison, grade 1 = 7.7%, grade 2 = 0%). The current study confirms the higher prevalence of WMH in subjects with bipolar disorder. Differences of small-sized WMH abnormalities between groups were successfully detected using a large number of bipolar subjects and thinner sliced MR images with FLAIR.     

White matter hyperintensities in mid-adult life

PURPOSE OF REVIEW: White matter hyperintensities on T2-weighted magnetic resonance imaging are frequent incidental findings in the brains of elderly individuals. Recent studies have reported that they may also be common in middle-aged individuals, and their systematic evaluation in younger populations is necessary. RECENT FINDINGS: Incidental white matter hyperintensities are common in brains of healthy individuals in their 60s and may be seen as early as the 30s and 40s. They are associated with subtle functional impairment and higher prevalence of neuropsychiatric disorders. While cerebrovascular risk factors such as hypertension, diabetes, high homocysteine, and so forth, are known risk factors for white matter hyperintensities, a significant proportion of the variance is unexplained. Genetic factors, alone or in interaction with environmental factors, appear to be important. There is a slight excess of white matter hyperintensities in women, the basis for which is not understood. Longitudinal studies show that those with baseline lesions have a greater progression over time. SUMMARY: New imaging techniques present an opportunity to examine white matter pathology in great detail in younger populations. Standardized methods to examine such pathology and its determinants will help inform strategies for their prevention, which is an important component of a healthy ageing agenda.     

Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease

A variety of anatomic and functional neuroimaging findings are associated with Alzheimer's disease (AD). One of the strongest imaging associations identified is between AD and hippocampal atrophy. The ∈4 allele of the apolipoprotein E (ApoE) gene increases the risk of developing AD and lowers the mean age of onset of the disease. The purpose of this study was to assess the association between hippocampal volume and ApoE polymorphisms in elderly control subjects and in patients with probable AD. We performed magnetic resonance imaging–based volume measurements of the hippocampus in 125 cognitively normal elderly controls and 62 patients with probable AD. ApoE genotyping was performed by using standard methods. Hippocampal volumes were significantly smaller in AD cases than in control subjects. Hippocampal volumes did not differ significantly within either clinical group on the basis of ApoE genotype. Both the ∈4 allele of ApoE and hippocampal atrophy were significantly but independently associated with AD.