Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
J Neurol Neurosurg Psychiatry. 2023 Sep;94(9):670-680. doi: 10.1136/jnnp-2022-331034. Epub 2023 Jul 6.
While obesity in midlife is a risk factor for dementia, several studies suggested that obesity also protected against dementia, hence so-called obesity paradox. The current study aims to address the relationship between apolipoprotein E () genotype and obesity in dementia.
Clinical and neuropathological records of the National Alzheimer's Coordinating Center (NACC) in the USA, which longitudinally followed approximately 20 000 subjects with different cognitive statues, genotype and obesity states, were reviewed.
Obesity was associated with cognitive decline in early elderly cognitively normal individuals without , especially those with . Neuropathological analyses adjusted for dementia status showed that carriers tended to have more microinfarcts and haemorrhages due to obesity. On the other hand, obesity was associated with a lower frequency of dementia and less cognitive impairment in individuals with mild cognitive impairment or dementia. Such trends were particularly strong in carriers. Obesity was associated with fewer Alzheimer's pathologies in individuals with dementia.
Obesity may accelerate cognitive decline in middle to early elderly cognitive normal individuals without likely by provoking vascular impairments. On the other hand, obesity may ease cognitive impairment in both individuals with dementia and individuals at the predementia stage, especially those with , through protecting against Alzheimer's pathologies. These results support that genotype modifies the obesity paradox in dementia.
中年肥胖是痴呆的一个危险因素，但有几项研究表明肥胖也能预防痴呆，因此出现了所谓的“肥胖悖论”。本研究旨在探讨载脂蛋白 E () 基因型与痴呆症中肥胖的关系。
对美国国家老年痴呆症协调中心 (NACC) 的临床和神经病理学记录进行了回顾，该中心对约 20000 名具有不同认知状态的受试者进行了纵向随访，这些受试者的 基因型和肥胖状态均有记录。
肥胖与认知正常的早期老年个体的认知能力下降有关，尤其是那些不携带 的个体。经过痴呆状态调整的神经病理学分析表明，肥胖会导致携带 的个体更容易出现微梗死和出血。另一方面，肥胖与轻度认知障碍或痴呆患者的痴呆症和认知障碍频率降低有关。在携带 的个体中，这种趋势尤为明显。肥胖与痴呆患者的阿尔茨海默病病理变化较少有关。
肥胖可能会通过引发血管损伤，加速中年至早期认知正常的无 个体的认知能力下降。另一方面，肥胖可能会通过预防阿尔茨海默病病理变化，减轻痴呆患者和痴呆前期个体的认知障碍，尤其是携带 的个体。这些结果支持 基因型可调节痴呆症中的肥胖悖论。
