COGNITIVE DECLINE IN A PRIMATE MODEL OF CEREBROVASCULAR DISEASE

高血压，老年人甚至中年人的常见病 成年人长期以来一直与认知功能障碍有关，尤其是 在记忆领域。然而，这一现象的神经生物学基础 对减损的理解还不是很清楚。这个项目将决定 已知有脑血管疾病风险的猴子的认知效应 仅由高血压引起的，或与致动脉粥样硬化的饮食相结合。我们 计划使用行为任务评估猴子的认知功能 它们是为神经心理学电池而开发或改编的 我用来评估老年人口，特别是， 脑血管疾病患者。猴子的表演将会 每隔6个月进行一次队列跟踪，时间间隔为12或48年 月份。在这件事上，认知功能的变化概况， 包括记忆、执行功能(认知灵活性、注意力、 视觉空间功能和心理测量速度)将被确定。我们 预计会看到可测量的认知障碍，主要是在记忆方面 功能，单独作为高血压的结果，或在 与致动脉粥样硬化饮食相结合，但不能单独从致动脉粥样硬化饮食中获得。 这一变化应在诱导后12个月内观察到 高血压伴或不伴维持动脉粥样硬化饮食。我们预计 高血压的长期后果(48个月)会产生 记忆功能的进行性下降以及在 其他认知领域包括执行系统功能、视觉 能力和注意力，实际上产生了脑血管 痴呆症。我们预计患有高血压的猴子合并 导致动脉粥样硬化的饮食也会发展成痴呆症状态，但由于 局灶性神经病理的可能差异，缺陷的模式可能 比只有高血压的情况更具变异性。48个月 对该项目中猴子的子集进行行为评估将允许 美国将确定12个月后是否出现早期认知变化 是否会发展到类似标准所定义的“痴呆”状态？ 用于治疗人类痴呆症的药物。此外，认知的变化 在这个项目中绘制的图表将与解剖、成像和 从相同的动物身上收集的神经病理数据来确定 这些变量之间的关系程度。此方法可能会 还允许识别相关的行为或 认知障碍的神经生物学标记物与脑血管 痴呆症。此外，认知能力下降的综合指数将是 与磁共振和正电子发射计算机断层扫描的总体变化指数相关 动物。通过这种方式，我们将能够确定新陈代谢 正电子发射计算机断层扫描发现的功能减退先于或伴随 认知障碍。也是行为发现的综合指数 因为个人领域中的变化将与存在相关 血脑屏障的损害及其程度和模式 视网膜病变。最后，认知能力下降与 将测量收缩压和血清胆固醇水平。

Hypertension, a common condition among the elderly and even middle aged adults, has long been associated with cognitive dysfunction, particularly in the domain of memory. However, the neurobiological basis for this impairments is not well understood. This project will determine the cognitive effects on monkeys at known risk for cerebrovascular disease from hypertension alone, or in combination with an atherogenic diet. We plan to assess the cognitive function of monkeys using behavioral tasks which were developed for, or adapted from neuropsychological batteries used i the evaluation of geriatric populations and, in particular, patients with cerebrovascular disease. The performance of monkeys will be followed in cohorts at six months intervals for either 12 or 48 months. In this matter, a profile of change in cognitive function, including memory, executive function (cognitive flexibility, attention, visuospatial function and psychometric speed) will be determined. We expect to see measurable cognitive impairment, primarily in memory function, occurring as a consequence of hypertension alone, or in combination with atherogenic diet, but not from atherogenic diet alone. This change should be observable by 12 months following induction of hypertension with or without maintenance on atherogenic diet. We expect the long term consequences (48 months) of hypertension to produce a progressive decline in memory function as well as produce impairments in other cognitive domains including executive system function, visuopatial abilities and attention, producing, in effect, a cerebrovascular dementia. We expect that monkeys with hypertension combined with atherogenic diet will also develop a dementia state, but, owing to possible differences in focal neuropathology, the pattern of deficits may be more variable than that found with hypertension alone. The 48 month behavioral assessment of a subset of monkeys in this project will allow us to determine whether early cognitive changes identified at 12 months will progress toward a "dementia" state, as defined by criteria parallel to those for dementia in humans. Furthermore, the changes in cognition charted in this project will be correlated with anatomical, imaging and neuropathological data collected from the same animals to determine the extent of the relationship between these variables. This approach may also permit the identification of a relevant behavioral or neurobiological marker of cognitive impairment and cerebrovascular dementia. Further, a composite index of cognitive decline will be correlated with an overall index of changes on MRI and PET in the same animals. In this manner, we will be able to determine if metabolic hypofunction identified on PET precedes or occurs concomitantly with cognitive impairment. A composite index of behavioral findings as well as changes in individuals domains will be correlated with the presence of blood brain barrier compromise the and extent and pattern of retinopathy. Finally, the relationship between cognitive decline, systolic blood pressure and serum cholesterol level will be measured.