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      White Matter Changes in Patients with Alzheimer’s Disease and Associated Factors

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          Abstract

          Alzheimer’s disease (AD) is traditionally thought of as a neurodegenerative disease. Recent evidence shows that beta amyloid-independent vascular changes and beta amyloid-dependent neuronal dysfunction both equally influence the disease, leading to loss of structural and functional connectivity. White matter changes (WMCs) in the brain are commonly observed in dementia patients. The effect of vascular factors on WMCs and the relationship between WMCs and severity of AD in patients remain to be clarified. We recruited 501 clinically diagnosed probable AD patients with a series of comprehensive neuropsychological tests and brain imaging. The WMCs in cerebral CT or MRI were rated using both the modified Fazekas scale and the combined CT-MRI age related WMC (ARWMC) rating scale. Periventricular WMCs were observed in 79.4% of the patients and deep WMCs were also seen in 48.7% of the patients. WMC scores were significantly higher in the advanced dementia stage in periventricular WMCs ( p = 0.001) and total ARWMCs ( p < 0.001). Age and disease severity were both independently associated with WMCs score, particularly in the total, frontal and parieto-occipital areas. Vascular factors including hypertension, diabetes mellitus, and gender were not significantly associated with WMCs. In conclusion, both age and severity of dementia were significantly associated with WMCs in AD patients. These associations highlight future research targets.

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          A new rating scale for age-related white matter changes applicable to MRI and CT.

          L Wahlund, F. Barkhof, F Fazekas … (2001)
          MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT. Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using kappa statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas. Interrater reliability was good for MRI (kappa=0.67) and moderate for CT (kappa=0.48). MRI was superior in detection of small ARWMC, whereas larger lesions were detected equally well with both CT and MRI. In the parieto-occipital and infratentorial areas, MRI detected significantly more ARWMC than did CT. In the frontal area and basal ganglia, no differences between modalities were found. When a fluid-attenuated inversion recovery sequence was used, MRI detected significantly more lesions than CT in frontal and parieto-occipital areas. No differences were found in basal ganglia and infratentorial areas. We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity, except for certain regions. The interrater reliability was slightly better for MRI, as was the detectability of small lesions.
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            Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

            D Snowdon, L Greiner, J A Mortimer … (1997)
            To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Convents in the Midwestern, Eastern, and Southern United States. A total of 102 college-educated women aged 76 to 100 years. Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
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              A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study.

              E Englund, A Brun (1986)
              In cases of Alzheimer's presenile and senile dementia, Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT), respectively, we have observed, in addition to the gray matter degeneration, a lesion that has the character of an incomplete infarction confined to the white matter. It is encountered in 60% of both groups, with mild changes in two thirds and moderate or severe changes in one third. It involves the deep white matter symmetrically, tapering off toward the cortex. It is characterized by partial loss of myelin, axons, and oligodendroglial cells; mild reactive astrocytic gliosis; and sparsely distributed macrophages as well as stenosis resulting from hyaline fibrosis of arterioles and smaller vessels. No complete or cavitating infarctions and no hypertensive vascular changes were observed. The white matter changes are thought to be due to hypoperfusion of the concerned white matter territories since, in addition to the white matter hyaline vascular stenosis, these cases show signs of cardiovascular disease, usually with hypotension. The white matter disorder also occurs independent of the gray matter process of AD and SDAT and may be seen as the sole brain lesion in non-AD subjects. Its occurrence is thus neither regularly related to the severity nor to the regional appearance and accentuation of the cortical Alzheimer process and is thus not likely to be just the result of a wallerian degeneration. Histologically it is similar in several respects to Binswanger's disease, although with some distinct differences. It is thus related to the cerebrovascular group of disorders in addition to AD and SDAT. In view of its frequency and severity, this white matter lesion is important to define, to diagnose, and ultimately to prevent or cure.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Clin Med
                Journal ID (iso-abbrev): J Clin Med
                Journal ID (publisher-id): jcm
                Title: Journal of Clinical Medicine
                Publisher: MDPI
                ISSN (Electronic): 2077-0383
                Publication date (Electronic): 01 February 2019
                Publication date Collection: February 2019
                Volume: 8
                Issue: 2
                Electronic Location Identifier: 167
                Affiliations
                [1 ]Department of Neurology, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin 640, Taiwan; blueggobi@ 123456gmail.com
                [2 ]Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City 801, Taiwan; neuro.chou@ 123456gmail.com
                [3 ]Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; mp245@ 123456ms49.hinet.net
                [4 ]Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
                [5 ]Department of Neurology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung City 812, Taiwan
                [6 ]Department of and Master’s Program in Neurology, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
                [7 ]Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
                Author notes
                [* ]Correspondence: endlessyhy@ 123456gmail.com ; or endless@ 123456kmu.edu.tw ; Tel.: +886-7-3162158
                Article
                Publisher ID: jcm-08-00167
                DOI: 10.3390/jcm8020167
                PMC ID: 6406891
                PubMed ID: 30717182
                SO-VID: b1e94429-4a6f-49aa-a1a9-ab82ed4f0dd7
                Copyright © © 2019 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 31 December 2018
                Date accepted : 26 January 2019
                Categories
                Subject: Article

                Keywords: alzheimer’s disease,age,diabetes mellitus,hypertension,leukoaraiosis,white matter changes,vascular risk factor
                Data availability:
                Keywords: alzheimer’s disease, age, diabetes mellitus, hypertension, leukoaraiosis, white matter changes, vascular risk factor

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