May 18, 2007 — 一项来自佛明罕后代试验的新研究结果显示，
临床前失智症病患的初期，非健忘轻度认知受损相关的决策能力受损（MCI-EF）可能发生在失忆前；除此之外，核磁共振造影（MRI）上，见到的脑部结构变化可以早期区分出MCI-EF与健忘性MCI（MCI-A）。
然而，在这个年龄族群，没有任何MRI评量达到MCI-A的显著性。
【何者先发生？】
研究者麻州波士顿大学Rhoda Au博士向Medscape表示，在记忆力受损前，可能先发生决策能力的下降，但是因为这是个非常复杂且不容易发现的问题，这些个体可能不会察觉他们的记忆力正在下降。
根据Au博士表示，目前为止，已经有许多试验研究显示，认知功能下降临床症状与病征老年病患，其脑部结构变化与认知功能受损之间的关系。
传统上，MCI-EF已经被认为与白质高密度（WMH）有关，且被认为会增加血管失智的风险；另一方面，MCI-A，广泛地被认为是阿兹海默症（AD）的前驱症状，其特征为海马回体积较小。
为了确认MRI测量是否可以区分中年、非失智个体的MCI-A与MCI-EF，1850位来自佛明罕后代研究的健康受试者接受脑部MRI与神经精神测试。
神经精神筛选的定义为一群非MCI控制组包含1602位没有记忆或是决策功能缺失的受试者，其他的受试者中，115位有MCI-A，而133位有MCI-EF；每个因子的受损以低于年龄、性别与教育程度组平均的1.5个标准差定义。
【早期介入的机会】
包括TCBV、WMH与海马回脑部容积（HBV）的脑部MRI测量，接着与有明显MCI且被分为两组，65岁以下与65岁以上的受试者相连。
Au博士表示，我们的结果显示，那些65岁以上受试者的结果与其他研究的相符；相较于那些无MCI的病患，这两种MCI亚型都与较小的TCBV有关；除此之外，那些记忆受损的病患，其海马回体积较小的可能性将近高出两倍；相对的，那些决策功能缺失的病患，其WMH较大的可能性高出将近三倍。
事实上，研究者表示，广泛性WMH体积的研究受试者，发生MCI-EF的风险相较于年龄较高发生MCI-A的风险高出五倍。
这项研究的重要性在于MRI标记延伸到那些65岁以下病患，相较于控制组，那些决策功能下降50%的，更可能有较小的TCBV，然而，针对有记忆受损的病患，没有任何MRI的评量达到显著差异。
根据Au博士表示，研究者将会继续追踪这群病患，以确定怎样的受试者会演变成失智症；虽然目前仍然处于起始阶段，这项研究可能最终可以协助确认最早期、认知功能下降的临床前期，提供临床医师有效治疗，与或许最终可以预防失智症的机会。
Decline in Executive Functioning May Precede Memory Loss in Preclinical Dementia
By Caroline Cassels
Medscape Medical News
May 18, 2007 — New research from the Framingham Offspring Study suggests that impaired executive function associated with nonamnestic mild cognitive impairment (MCI-EF) may precede memory loss in the earliest stages of preclinical dementia. Furthermore, structural brain changes visible on magnetic resonance imaging (MRI) can differentiate between MCI-EF and amnestic MCI (MCI-A) as early as middle age.
Presented here at the American Academy of Neurology 59th Annual Meeting, results from the National Institutes of Health–funded study showed smaller total cerebral brain volume (TCBV) in individuals with MCI under the age of 65 years was associated with a 2-fold increased risk for executive-function impairment compared with controls. However, no MRI measures reached significance for MCI-A among individuals in this age group.
Which Comes First?
"It may be that a decline in executive functioning precedes memory impairment, but because it is a more complex and subtle condition, individuals may not be as aware of it as they are of memory loss," study investigator Rhoda Au, PhD, from Boston University School of Medicine, in Massachusetts, told Medscape.
According to Dr. Au, to date, most of the research demonstrating a relationship between structural brain changes and cognitive impairment has been conducted in older individuals who are already experiencing clinical signs and symptoms of cognitive decline.
Traditionally MCI-EF has been associated with white-matter hyperintensities (WMH) thought to increase the risk for vascular dementia. On the other hand, MCI-A, which is widely considered to be a prodrome of Alzheimer's disease (AD), is characterized by smaller hippocampal volume.
To determine whether MRI measures can distinguish between MCI-A and MCI-EF in middle-aged, nondemented individuals, 1850 healthy subjects from the Framingham Offspring Study underwent brain MRI and neuropsychological testing.
Neuropsychological screening defined a non-MCI control group of 1602 subjects with no memory or executive-function deficits. Of the remaining subjects, 115 had MCI-A and 133 had MCI-EF. Impairment for each factor was defined as 1.5 standard deviation below age-, sex-, and education-adjusted group means.
Early-Intervention Opportunity
Brain MRI measures, which included TCBV, WMH, and hippocampal brain volume (HBV), were then related to study subjects with prevalent MCI who were divided by age into 2 groups — those older and those younger than 65 years.
"Our results for those 65 years and older are consistent with what other studies find," said Dr. Au. "Compared with those without MCI, smaller TCBV was found for both MCI subtypes. Further, those with memory impairments were nearly twice as likely to have smaller hippocampal volume. In contrast, those with executive-function deficits were almost 3 times more likely to have large WMH."
In fact, the researchers report that study subjects with extensive WMH volume had a 5-fold increased risk for MCI-EF vs MCI-A among older individuals.
The significance of this study was that MRI markers extended to those who were under age 65 years. Compared with controls, those with executive-function deficits were 50% more likely to have smaller TCBV, whereas no MRI measures reached significance for the group with memory impairments.
According to Dr. Au, the investigators will continue to follow the cohort to determine which subjects will progress to dementia. Although still in its initial stages, this research may eventually help identify patients in the earliest, preclinical stages of cognitive decline, providing clinicians with the opportunity to effectively treat and perhaps eventually prevent dementia.
American Academy of Neurology 59th Annual Meeting: Abstract S01.006. April 28 – May 5, 2007.
作者：
Caroline Cassels 2007-6-16