Divisions of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Neuroepidemiology. 2010;34(4):200-7. doi: 10.1159/000289351. Epub 2010 Mar 3.
Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline among healthy, community-dwelling older men without diabetes.
Fasting plasma insulin and C-peptide (insulin secretion) levels were measured in 1,353 nondiabetic men, aged 60-92 years (mean = 71.3 years), in the Physicians' Health Study II, who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range = 1.5-4.0 years) using telephone-based tests (general cognition, verbal memory and category fluency). Primary outcomes were the Telephone Interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging 4 verbal tests). Multivariable linear regression models were used to estimate the relations of insulin and C-peptide to cognitive decline.
Higher fasting insulin was associated with a greater decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency, e.g. the multivariable-adjusted mean difference (95% CI) in decline for men with the highest versus lowest insulin levels was -0.62 (-1.15, -0.09) points on the TICS (p for trend = 0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was a greater decline across all tests with increasing C-peptide, but the findings were statistically significant only for the global score (p for trend = 0.03).
Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.
2 型糖尿病与晚年认知能力下降有关；而对于无糖尿病的人群，胰岛素水平和胰岛素分泌与认知变化之间的关系则知之甚少。我们前瞻性地研究了健康的、社区居住的老年男性中，空腹胰岛素水平和胰岛素分泌与无糖尿病者认知下降之间的关系。
在“医师健康研究 II”中，对 1353 名年龄在 60-92 岁（平均年龄为 71.3 岁）、无糖尿病的男性进行了空腹血浆胰岛素和 C 肽（胰岛素分泌）水平的检测，这些人在平均 3.3 年后参加了认知测试。使用基于电话的测试（一般认知、语言记忆和类别流畅性），两次评估相隔 2 年（范围为 1.5-4.0 年）进行。主要结局指标是电话认知状态测试（TICS）、总体认知和语言记忆（4 项语言测试的平均值）。采用多变量线性回归模型来估计胰岛素和 C 肽与认知下降的关系。
调整后，空腹胰岛素水平较高与所有测试的下降均相关。结果在 TICS 和类别流畅性方面具有统计学意义，例如，胰岛素水平最高与最低的男性在 TICS 上的下降差值为 -0.62（-1.15，-0.09）点（趋势检验的 p 值=0.04）；这一差异与年龄相差 7 岁的男性相似。同样，随着 C 肽的增加，所有测试的下降程度都有所增加，但仅在总体评分方面具有统计学意义（趋势检验的 p 值=0.03）。
在老年男性中，空腹胰岛素水平较高和胰岛素分泌增加可能与整体认知下降有关，即使在没有糖尿病的情况下也是如此。
