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September 12, 2006 -- 一篇新的研究发现，年长者的认知抱怨，可能意指潜在的神经退化改变，即使神经精神测验结果正常亦然。
Dartmouth 医学院的研究者发现，抱怨有显著记忆问题但记忆测验分数正常者，有3%出现灰质(GM)密度减少，而诊断为轻度认知缺损(MCI)的病患则有4%出现灰质(GM)密度减少。
主要研究者心理学博士Andrew Saykin向Medscape表示，我们的资料认为这些之前被医师认为是“困扰的正常人（worried well）”的人，实际上自觉有所改变，而我们所认为的具有敏感度的测验却不足以侦测出这些微妙的改变。
本报告刊登于九月12日的神经学期刊。
本研究包含“Dartmouth记忆与年纪研究(Dartmouth Memory and Aging Study)”中120位年纪60岁以上的持续观察个案，Dartmouth记忆与年纪研究是一项持续进行的纵向研究。
研究者对40位尚有胸腺且有认知抱怨而神经精神测验正常者，和40位MCI失忆病患以及40位健康控制(HC)者使用核磁共振(MRI) 扫描比较脑部构造，以及逐像素形态分析方法(voxel-based morphometry)和海马回体积分析(hippocampal volume analysis)。
【GM密度减少】
相较于HC组，认知抱怨和MCI组在全脑分析显示相似型态的GM减少，在两侧中颞叶、额叶和其他新皮质区则各有不同证据。
此外，全部研究对象的左右海马回之GM密度减少者均伴有高度认知抱怨；Saykin博士表示，许多之前的研究采取过于简单的方法来评估认知缺损，有许多案例显示，病患仅被问及是否有任何记忆问题。
不过，在此一研究中，研究者使用一种有不同量表的蓄电池来评估自我以及旁观者之认知功能观点，且直接将这些结果和个别之GM密度作比较—而这些是以前所未曾做过的。
【圣杯】
本研究中所观察到之GM密度改变的型态指出了脑部构造的改变，和MCI所见相似，甚至出现在认知完好、无忧郁症而有显著记忆抱怨之年长者的情况之下，此一发现意味着极早期之失智和构成MCI前期。
他指出，我们的资料显示灰质密度有许多改变时，代表认知抱怨之早期现象，出现在脑容量损失之前，最典型的特征就是MCI和阿兹海莫症。
Saykin博士表示，此一发现或许可以提供医师们有机会在这些病程早期即介入— 这项目标已经很快地变成失智症治疗和预防策略的“圣杯”。
他认为，世上有许多新的神经保护制剂，将可使及早诊断更显关键。
【对所有人都进行MRI？】
Saykin博士表示，基于这些发现，医师遇到认知抱怨病患时应严肃面对— 特别是有其他导致记忆损失的潜在原因时，如忧郁症。
除此之外，健康之无忧郁症的年长者，但有显著自我体察或旁观者发现有认知抱怨时，应接受包括临床评估和认知测验等详细评估。
他表示，我们的研究并没有必要去说服纳税者负担这些个案的MRI费用，我认为这一点在未来会被加以考量，因为MRI对早期症状的确是非常有敏感度，不过，就这一点还需要更多的研究，以便加以确认。
Saykin博士和他的团队将持续追踪这些研究对象，以确定哪一部份认知抱怨者会发展成为MCI和阿兹海默症或者其他失智症。
此外，他表示，他们计划未来发展神经精神和神经影像方法来帮助评估认知功能、脑部构造改变过程，以及每一组的诊断结果。
Memory Complaints May Signal Brain Loss
By Caroline Cassels
Medscape Medical News
September 12, 2006 — Cognitive complaints in older adults may indicate underlying neurodegenerative changes, even in the presence of normal neuropsychological test results, a new study has found.
Investigators at Dartmouth Medical School in Lebanon, New Hampshire found that individuals who complained of significant memory problems but who had normal memory testing scores had a 3% reduction in gray-matter (GM) density compared with a 4% reduction among patients diagnosed with mild cognitive impairment (MCI).
"Our data suggest these individuals, who were previously dismissed by many clinicians as the 'worried well,' are actually detecting changes within themselves and that what we thought were quite sensitive tests are not able to detect these subtle changes," principal investigator Andrew Saykin, PsyD, told Medscape.
The report is published in the September 12 issue of Neurology.
The study included 120 consecutive subjects over age 60 years enrolled in the Dartmouth Memory and Aging Study — an ongoing, longitudinal study.
Using magnetic resonance imaging (MRI), investigators compared the structural brain scans of 40 euthymic individuals with cognitive complaints who had normal neuropsychological test performance with 40 patients with amnestic MCI patients and 40 healthy controls (HC) using voxel-based morphometry and hippocampal volume analysis.
Decreased GM Density
Compared with the HC group, the cognitive-complaint and MCI groups showed similar patterns of decreased GM on whole-brain analysis, with differences evident in the bilateral medial temporal, frontal, and other neocortical regions.
In addition, higher levels of cognitive complaints were associated with decreased GM density in the left and right hippocampi across the entire study sample. Many previous studies, said Dr. Saykin, have taken a simplistic approach to the assessment of cognitive complaints. In many cases, patients were simply asked whether they had any memory problems.
However, in this study, investigators used a battery of different scales to assess self and informant perceptions of cognitive function and directly compared these results with individuals' GM density — something that has not been done before, he said.
Holy Grail
The pattern of GM density change observed in the study indicates structural brain changes, similar to those seen in MCI, are present even in cognitively intact, nondepressed older adults with significant memory complaints — a finding that may signify a very early stage of the dementia process and constitute a pre-MCI stage.
"Our data suggest there are a lot of changes in the gray-matter density that show up earlier in the cognitive-complaint group, before brain volume loss, which typically characterizes MCI and Alzheimer's disease," he said.
This finding, said Dr. Saykin, may provide clinicians with the opportunity to intervene at a very early stage in the disease process — an objective that is fast becoming the "holy grail" of dementia treatment and prevention strategies.
"There are many new neuroprotective agents on the horizon that will make earlier diagnosis more critical than ever," he said.
MRI for All?
Based on these results, said Dr. Saykin, it is clear that clinicians who encounter patients with cognitive complaints should take them very seriously — particularly when other potential causes of memory loss, such as depression, have been eliminated.
"Otherwise-healthy, nondepressed elderly people with significant self-perceived and informant-perceived cognitive complaints should undergo a careful assessment that includes clinical evaluation and cognitive testing.
"While our study alone wouldn't necessarily convince potential payers to cover the cost of an MRI in such individuals, I think in the future this will need to be considered, because MRI does appear to be sensitive to very early stages. However, at this point we need more research to validate this finding," he said.
Dr. Saykin and his team will continue to follow the study group over time to determine, among other things, what proportion of those with cognitive complaints develop MCI and ultimately Alzheimer's disease or other type of dementia.
In addition, he said, they plan to further develop neuropsychological and neuroimaging methods to help evaluate cognitive functioning, progression of structural brain changes, and diagnostic outcomes within each group.
Neurology. 2006;67:834-842.