Cognitive decline and diabetes: a systematic review of the neuropathological correlates accounting for cognition at death

神经病理学 脑淀粉样血管病 认知功能衰退 海马硬化 神经退行性变 医学 糖尿病 病理 高强度 痴呆 疾病 阿尔茨海默病 血管病 认知 内科学 心理学 精神科 颞叶 内分泌学 磁共振成像 癫痫 放射科
作者
Gina Hadley,Jiali Zhang,Eva Harris-Skillman,Zoi Alexopoulou,Gabriele C. DeLuca,Sarah T. Pendlebury
出处
期刊:Journal of Neurology, Neurosurgery, and Psychiatry [BMJ]
卷期号:93 (3): 246-253 被引量:21
标识
DOI:10.1136/jnnp-2021-328158
摘要

Given conflicting findings in epidemiologic studies, we determined the relative contributions of different neuropathologies to the excess risk of cognitive decline in diabetes mellitus (DM) through a systematic review of the literature. Included studies compared subjects with and without DM and reported neuropathological outcomes accounting for cognition at death. Data on Alzheimer’s disease (AD) pathology, cerebrovascular disease and non-vascular, non-AD pathology were extracted from each study. Eleven studies (n=6 prospective cohorts, n=5 retrospective post-mortem series, total n=6330) met inclusion criteria. All 11 studies quantified AD changes and 10/11 measured cerebrovascular disease: macroscopic lesions (n=9), microinfarcts (n=8), cerebral amyloid angiopathy (CAA, n=7), lacunes (n=6), white matter disease (n=5), haemorrhages (n=4), microbleeds (n=1), hippocampal microvasculature (n=1). Other pathology was infrequently examined. No study reported increased AD pathology in DM, three studies showed a decrease (n=872) and four (n= 4018) showed no difference, after adjustment for cognition at death. No study reported reduced cerebrovascular pathology in DM. Three studies (n=2345) reported an increase in large infarcts, lacunes and microinfarcts. One study found lower cognitive scores in DM compared to non-DM subjects despite similar cerebrovascular and AD-pathology load suggesting contributions from other neuropathological processes. In conclusion, lack of an association between DM and AD-related neuropathology was consistent across studies, irrespective of methodology. In contrast to AD, DM was associated with increased large and small vessel disease. Data on other pathologies such as non-AD neurodegeneration, and blood-brain-barrier breakdown were lacking. Further studies evaluating relative contributions of different neuropathologies to the excess risk of DM are needed.
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