OLFACTORY IDENTIFICATION DEFICITS AS AN EARLY MARKER OF MILD COGNITIVE IMPAIRMENT

帕金森氏病(PD)患者有僵直、运动迟缓、静止性震颤和步态障碍。在许多不符合帕金森氏症诊断资格的正常老年人中，这些相同的迹象也可能在一定程度上出现(即轻度帕金森氏征[MPS])。MPS存在于30%-40%的正常老年人中，与死亡风险增加两倍相关，是阿尔茨海默病(AD)发病的早期标志。一个类似的例子可能是 MPS和轻度认知障碍(MCI)之间的差异，因为这两个实体都可能代表AD事件的标志物。 虽然MCI一直是密集调查的对象，但MPS几乎没有受到关注。因此，关于议员的问题有很多悬而未决的问题。首先，只有一小部分患有MPS的人会患上阿尔茨海默病。尚不清楚为什么一些MPS患者会继续发展为AD，而其他人则不会。这与AD的已知风险因素之间的关系尚未得到研究。第二，国会议员的长期功能后果是什么？第三，什么是 MPS的神经解剖学基础以及是否有证据表明基底节受累？没有神经成像数据比较患有MPS的人和年龄相近的没有MPS的人。这项研究将利用WHICAP II队列。主要目的1是研究MPS与AD危险因素在增加AD发病风险中的关系。基线评估的AD危险因素包括：年龄、性别、痴呆症家族史、头部损伤史、 教育程度、雌激素使用和载脂蛋白水平。我们假设，有MPS和其他基线AD危险因素的受试者在随访期间发生AD的风险最大。主要目的2是研究MPS在纵向环境下的功能影响。我们假设MPS在基线水平的受试者，特别是基线时轴向功能区的异常，在随访期间将表现出更快的功能下降，并且MPS的变化率将与功能的变化率相关。主要目的3是利用磁共振成像(MRI)研究1,000名非痴呆受试者的神经解剖学基础，这些受试者将在时间2接受扫描。我们假设，与没有MPS的受试者相比，患有MPS的受试者在MRI评估的基底节的代谢活动减少，与既没有MPS也没有代谢活动减少的受试者相比，患有MPS且基底节代谢活动减少的受试者发生AD的风险增加。随着我们治疗痴呆症的能力的提高，我们对识别患有MPS的个体以及了解这一实体及其与痴呆症的关系的兴趣将相应增加。在这个提案中，我们提出了三个研究目标，以解决关于MPS的基本未知问题。

Patients with Parkinson's disease (PD) have rigidity, bradykinesia, resting tremor and gait disturbance. These same signs may also be present to a mild degree in many normal elderly individuals who do not qualify for a diagnosis of PD, (i.e., mild Parkinsonian signs [MPS]). MPS are present in 30 - 40% of normal elderly individuals, are associated with a two-fold increased risk of mortality, and are an early marker for incident Alzheimer's disease (AD). A parallel may be drawn between MPS and mild cognitive impairment (MCI), as both entities may represent markers for incident AD. Whereas MCI has been the subject of intense investigation, MPS has received little attention. As a consequence, there are many unanswered questions about MPS. First, only a fraction of the individuals with MPS develop incident AD mad it is not clear why some individuals with MPS go on to develop AD while others do not. How this relates to known risk factors for AD has not been studied. Second, what are the long-term functional consequences of MPS? Third, what is the neuro-anatomical basis for MPS and is there evidence of basal ganglia involvement? There are no neuro-imaging data comparing individuals with MPS to similarly-aged individuals without MPS. This study will utilize the WHICAP II cohort. Primary Aim 1 is to study the relationship between MPS and risk factors for AD in increasing the risk for AD. Risk factors for AD that were assessed at baseline were: age, gender, family history of dementia, history of head injury, education, estrogen use, and APOE status. We hypothesize that subjects that have MPS as well as other baseline AD risk factors will be at the greatest risk for incident AD during follow-up. Primary Aim 2 is to study the functional impact of MPS in a longitudinal setting. We hypothesize that the subjects with MPS at baseline, and especially abnormalities in the axial function domain at baseline, will demonstrate more rapid decline in function during follow-up and that the rate of change in MPS will be associated with the rate of change in function. Primary Aim 3 is to study the neuroanatomical basis for MPS using magnetic resonance imaging (MRI) in 1000 non-demented subjects who will be scanned at Time 2. We hypothesize that subjects with MPS will demonstrate a reduction in MRI-assessed metabolic activity in the basal ganglia when compared with subjects without MPS and that subjects with MPS and a reduction of metabolic activity in the basal ganglia will be at increased risk for incident AD compared with subjects with neither MPS nor a reduction in metabolic activity. As our ability to treat dementia improves, there will be a corresponding increase in our interest in identifying individuals with MPS and in understanding this entity and its relationship to dementia. In this proposal, we set forth three research aims that will address basic unknowns about MPS.