Post-mortem brain studies reveal features of mild cognitive impairment

The brains of patients with mild cognitive impairment display pathologic features that appear to place them at an intermediate stage between normal aging and Alzheimer's disease, although some patients with mild cognitive impairment develop other types of dementia, according to two studies in the May issue of Archives of Neurology, one of the JAMA/Archives journals.

Mild cognitive impairment--difficulty with thinking, learning and memory--is increasingly recognized as a neurologic transition stage between normal cognitive function and Alzheimer's disease, according to background information in both articles. Older adults with mild cognitive impairment, especially those with a variety known as amnestic (memory-related) mild cognitive impairment, are thought to have a higher risk of progressing to clinical Alzheimer's disease. Little is known about how this condition affects the physical structures of the brain.

In the first study, Ronald C. Petersen, Ph.D., M.D., Mayo Clinic College of Medicine, Rochester, Minn., and colleagues compared the findings in autopsy tissue of brains of 15 individuals who at the time of their death had amnestic mild cognitive impairment (average age 88.9 years) to those of 28 individuals who were clinically healthy at the time of their death and 23 patients who were believed to have Alzheimer's disease at death and had undergone autopsy. The patients with mild cognitive impairment were examined every year before their death, which occurred between Sept. 1, 1986, and Dec. 31, 2004.

Most of the patients did not meet the requirements for a post-death diagnosis of Alzheimer's disease. However, the changes to their brains as compared to those of individuals without cognitive difficulties were more similar to those of patients with Alzheimer's disease. For instance, the patients had begun developing neurofibrillary tangles, or tangles in the cell bodies of neurons. The number of tangles correlated with the severity of the patient's symptoms at the last examination before death. The number of brain plaques, a hallmark of Alzheimer's disease, were similar in healthy patients and patients with mild cognitive impairment, indicating that the transition to Alzheimer's disease–related dementia may occur when these plaques form in more brain areas. All patients with mild cognitive impairment had abnormalities in their temporal lobes, which likely caused their cognitive difficulties, and many also had abnormalities in other areas that did not relate to the features of Alzheimer's disease.

"The neuropathologic features of amnestic mild cognitive impairment matched the clinical features and seemed to be intermediate between the neurofibrillary changes of aging and the pathologic features of very early Alzheimer's disease," the authors conclude.

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(Arch Neurol. 2006;63:665-672. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: This work was funded by the National Institute on Aging, a grant from the Mayo Alzheimer's Disease Patient Registry, and a grant from the Mayo Alzheimer's Disease Research Center and the Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program.

Editorial: Study Sheds Light on Features of Mild Cognitive Impairment

CHICAGO – Researchers can gain important information about the nature of mild cognitive impairment by correlating the symptoms patients experience when they are alive with the features of their brain after death, writes Harry V. Vinters, M.D., F.C.A.P., F.R.C.P.C., David Geffen School of Medicine at UCLA, in an accompanying editorial.

"The observation that amnestic mild cognitive impairment patients show 'early Alzheimer's disease' pathologic change within the central nervous system may not come as a great surprise, but it has now been firmly established by this important study," Dr. Vinters writes.

(Arch Neurol. 2006;63:645-646. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: The author is supported in part by grants from the National Institutes on Aging.

Patients with Mild Cognitive Impairment May Follow Different Paths to Dementia

Although many patients with amnestic mild cognitive impairment develop Alzheimer's disease, others develop unrelated forms of dementia, according to a related study in the same issue.

Gregory A. Jicha, M.D., Ph.D., also from the Mayo Clinic College of Medicine, Rochester, Minn., and colleagues analyzed the brains of 34 patients with mild cognitive impairment who had progressed to clinical dementia before their deaths. Twenty-eight of the participants had been diagnosed with Alzheimer's disease based on their symptoms.

Among the 34 participants included in the study analysis, 24 (71 percent) had brain abnormalities that qualified them for a diagnosis of Alzheimer's disease and 10 (29 percent) had brain features that suggested a primary diagnosis of dementia not related to Alzheimer's disease. These other types of dementia included Lewy body disease, in which abnormal round structures develop in areas of the brain that control thinking and movement, and hippocampal sclerosis, a type of dementia common in patients with epilepsy. As in the other study, all patients had abnormalities in their temporal lobes, which appeared to be related to their memory difficulties. Demographic characteristics or the degree of cognitive impairment did not differ between those who had developed Alzheimer's disease and those with different forms of dementia.

The study demonstrates the variation in causes of dementia following amnestic mild cognitive impairment, and suggests that existing tests need to be more sensitive to differentiate between those underlying abnormalities, the authors write. "No demographic or cognitive features predicted the final neuropathologic diagnoses of this cohort of subjects with dementia who transitioned from amnestic mild cognitive impairment," they conclude. "Moreover, none of the cognitive assessment measures used in this study predicted final pathologic findings. Further research using more detailed analyses of cognitive measurements and tests from the full neuropsychometric battery may be useful in predicting incipient Alzheimer's disease, allowing further refinement in the diagnostic criteria for amnestic mild cognitive impairment."

(Arch Neurol. 2006;63:674-681. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: This study was supported by grants from the National Institute on Aging and by the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program.

Editorial: Understanding Path to Alzheimer's Disease Key to Preventing the Condition

Insights from brain analyses may help physicians understand and eventually treat and prevent the development of Alzheimer's disease and other forms of dementia, writes Lawrence A. Hansen, M.D., UCSD School of Medicine, La Jolla, Calif., in a related editorial.

"If mild cognitive impairment usually heralds approaching dementia, and that dementia is usually Alzheimer's disease, then reversing mild cognitive impairment or even just prolonging it will have a huge impact on the societal burden of Alzheimer's disease," Dr. Hansen writes.

(Arch Neurol. 2006;63:647-648. Available pre-embargo to the media at www.jamamedia.org)

To contact editorialist Harry V. Vinters, M.D., F.C.A.P., F.R.C.P.C., call Elaine Schmidt at 310-794-2272. To contact editorialist Lawrence A. Hansen, M.D., call Debra Kain at 619-543-6163.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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