Pathologic Study of Intracranial Large Artery Atherosclerosis in 7260 Autopsy Cases
Introduction
Atherosclerosis of the intracranial large arteries, such as the internal carotid artery, anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), vertebral artery (VA), and basilar artery (BA), is one of the main causes of ischemic stroke.1 Intracranial large artery atherosclerosis (ICLAA) occurs more frequently in Asian, Hispanic, and African populations compared with the Caucasian ethnic group.2, 3, 4 Therefore, ICLAA may be an important pathologic condition in clinical settings in Japan. Several large autopsy series also found that ICLAA was associated with age, sex, hypertension, and diabetes mellitus.3, 5, 6, 7, 8
Recent studies have used noninvasive imaging modalities such as magnetic resonance angiography, computed tomographic angiography, and transcranial Doppler ultrasonography, rather than catheter angiography, for evaluating ICLAA in institution- or community-based healthy cohorts or ischemic stroke cases.9, 10, 11, 12, 13, 14, 15, 16, 17 However, there are some discrepancies between findings obtained by noninvasive imaging modalities and pathologic observations.18 Therefore, further studies examining the pathology of ICLAA at autopsy are required.
The risk factors for ICLAA include age,5, 6, 7, 11, 12, 17 race,2, 3 hypertension,3, 5, 6, 12, 17 diabetes mellitus,3, 10, 11, 12, 18, 19 and metabolic syndrome.19, 20 Of these, modifiable risk factors such as hypertension, diabetes mellitus, and metabolic syndrome can be well controlled by changes in lifestyle and medication. In the present study, we hypothesized that the ICLAA pathology of an individual is affected by the era of birth. Indeed, treatment of vascular risk factors, food trends, and living environment have changed over the last 50 years. Further, according to the Honolulu Heart Program,5 the incidence of ICLAA declined from 1965 to 1983. However, these data were obtained from only 198 cases, with a short observation period over 30 years. In our brain bank (Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology [TMGHIG], the Brain Bank for Aging Research, Tokyo, Japan), ICLAA has been regularly observed by neuropathologists in autopsy cases from 1972 to present.21 Thus, the aim of the present study was to determine the chronological changes in ICLAA in consecutive autopsy cases in Japanese subjects.
Section snippets
Case Selection
We analyzed 7260 autopsy cases from subjects ≥50 years old at the time of death from a total of 7307 consecutive Japanese autopsy cases at our Brain Bank for Aging Research. Autopsies were performed in our institute from May 1972 to March 2014. Our brain bank is an official division of the TMGHIG, a general hospital in the northern part of Tokyo that provides advanced medical services for aging individuals.
Severity of ICLAA
From 1972, we assessed ICLAA using autopsy materials after formalin fixation of the
Case Selection
From 1972 to 2014, we analyzed 7307 consecutive autopsy cases in our brain bank. As our brain bank is focused on aging individuals, the number of cases <50 years old at death was small. Thus, we only analyzed cases with an age ≥50 years at death in this study (total of 7260 cases; 3723 men, 3537 women; 51.3% men). A summary of cases is shown in Table 1. The mean age of all cases was 79.5 ± 8.7 years. The majority of cases were in their 70s and 80s at death, whereas a low number of individuals
Discussion
In the present study, we described the demographics of ICLAA in a longitudinal series of autopsy cases from the Brain Bank for Aging Research in Japan. The main findings were that the AS (sum of scores) and the percentage of cases with SA-ICLA (score 2 or 3) increased with age at death, that ICLAA was more severe in women than men in their 80s and 90s at death, and that the AS significantly decreased with later birth year.
Conclusions
Our analysis from a brain bank cohort in Japan showed that intracranial atherosclerosis advanced with age, with differences between sexes (i.e., more severe in men in their 60s at death, and more severe in women in their 80s and 90s at death). In addition, intracranial atherosclerosis was more severe in individuals born earlier, with the incidence of intracranial atherosclerosis decreasing in individuals who were born after the 1930s, independent of age at death.
Acknowledgments
We thank Ms. Yuuki Kimura, Ms. Mieko Harada, and Ms. Maki Obata for technical help.
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Grant support: This study was supported in part by the Comprehensive Brain Science Network (221S0003, SM, MT) and Japan Society for the Promotion of Science KAKENHI (JP 16H-06277).