Neuropathologic features of amnestic mild cognitive impairment.

BACKGROUND: The neuropathologic substrate of amnestic mild cognitive impairment (aMCI) is not known. OBJECTIVE: To determine the neuropathologic features of patients who died while their clinical classification was aMCI. DESIGN: Cohort study. SETTING: Community based. PARTICIPANTS: Sixty-six individuals, including 15 who had memory impairment beyond that allowed for aging but who were not demented, were studied along with 28 clinically healthy individuals and 23 patients with probable Alzheimer disease (AD) for comparison. MAIN OUTCOME MEASURES: Standard neuropathologic techniques and classification according to Khachaturian, Consortium to Establish a Registry for Alzheimer Disease, and National Institute on Aging-Reagan criteria were used to analyze autopsy tissue from 15 individuals who died while their clinical diagnosis was aMCI. For comparison, autopsy data on age-matched groups of clinically healthy individuals and patients with probable AD were analyzed. RESULTS: Most patients with aMCI did not meet the neuropathologic criteria for AD, but their pathologic findings suggest a transitional state of evolving AD. All the patients with aMCI had pathologic findings involving medial temporal lobe structures, likely accounting for their memory impairment. In addition, there were many concomitant pathologic abnormalities, including argyrophilic grain disease, hippocampal sclerosis, and vascular lesions. CONCLUSIONS: The neuropathologic features of aMCI matched the clinical features and seemed to be intermediate between the neurofibrillary changes of aging and the pathologic features of very early AD.

Survival study of vascular dementia in Rochester, Minnesota.

OBJECTIVE: To investigate the relationship between features and definitions of vascular dementia (VaD) and survival. DESIGN: We used the medical records linkage system of the Rochester Epidemiology Project to identify incident cases of dementia in Rochester from January 1, 1985, through December 31, 1989. Dementia and Alzheimer disease were defined using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Vascular dementia was defined by ad hoc criteria, including imaging. Each patient with dementia was matched by age and sex to a referent subject free of dementia. Patients with dementia and referent subjects were followed from the onset of dementia (or index year) through death, censoring, or the end of the study. RESULTS: We included 479 patients with incident dementia and 479 referent subjects. Overall, patients with VaD had worse mortality than referent subjects (relative risk [RR], 2.7; 95% confidence interval [CI], 1.9-3.9). Among patients with VaD, those with dementia temporally related to a stroke had a worse relative mortality (RR, 4.5; 95% CI, 2.7-7.4) than those with only imaging evidence of bilateral infarctions in gray matter structures (RR, 2.4; 95% CI, 1.5-3.8). Relative mortality estimates varied by using 3 sets of published diagnostic criteria for VaD. Patients with VaD had a higher RR of death (RR, 2.7; 95% CI, 1.9-3.9) than patients with dementia overall (RR, 1.8; 95% CI, 1.6-2.1) or patients with Alzheimer disease (RR, 1.4; 95% CI, 1.2-1.7). CONCLUSIONS: The relative mortality of patients with VaD varied depending on the set of diagnostic criteria used. A temporal relationship to a stroke was the strongest predictive feature for poor survival in patients with dementia.

Comparative diagnostic utility of different MR modalities in mild cognitive impairment and Alzheimer's disease.

This study compares the diagnostic accuracy of magnetic resonance (MR)-based hippocampal volumetry, single voxel (1)H MR spectroscopy ((1)H MRS) and MR diffusion-weighted imaging (DWI) measurements in discriminating patients with amnestic mild cognitive impairment (MCI), Alzheimer's disease (AD) and normally aging elderly. Sixty-one normally aging elderly, 24 MCI and 22 AD patients underwent MR-based hippocampal volumetry, (1)H MRS and DWI. (1)H MRS voxels were placed over both of the posterior cingulate gyri, and N-acetyl aspartate (NAA)/creatine (Cr), myoinositol (MI)/Cr and NAA/MI ratios were obtained. Apparent diffusion coefficient (ADC) maps were derived from DWI, and hippocampal borders were traced to measure hippocampal ADC. At 80% specificity, the most sensitive single measurement to discriminate MCI (79%) and AD (86%) from controls was hippocampal volumes. The most sensitive single measurement to discriminate AD from MCI was posterior cingulate gyrus NAA/Cr (67%). At high specificity (>85-90%), combinations of MR measures had superior diagnostic sensitivity compared with any single MR measurement for the AD vs. control and control vs. MCI comparisons. The MR measures that best discriminate more from less affected individuals along the cognitive continuum from normal to AD vary with disease severity. Selection of imaging measures used for clinical assessment or monitoring efficiency of therapeutic intervention should be tailored to the clinical stage of the disease.

Dementia and Alzheimer disease incidence rates do not vary by sex in Rochester, Minn.

BACKGROUND: Incidence rates of Alzheimer disease (AD) were higher in women than in men in several recent European and Asian studies. Cohort studies in the United States, on the other hand, have consistently reported no difference in incidence across sex. OBJECTIVE: To measure age- and sex-specific incidence rates of dementia and AD for persons aged 50 years and older residing in Rochester, Minn, during 1985 to 1989. SUBJECTS AND METHODS: Cases were ascertained through the medical records linkage system of the Rochester Epidemiology Project, which encompasses the records of all medical care providers (including outpatient clinics, hospitals, general practitioners, and nursing homes) in Rochester. Computer indices of clinical diagnoses, histologic diagnoses, and medical procedures were screened for indications of dementia. All medical records of potential cases were reviewed and abstracted by a trained nurse abstractor. A neurologist (E.K.) confirmed the presence of dementia and established a differential diagnosis of AD using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and estimated the year of onset. RESULTS: A total of 482 incident cases of dementia were identified; 356 of them (73.9%) had AD. For both dementia and AD, incidence rates increased steeply with age, and there were no consistent differences between men and women. The sex pattern for AD did not change after removing cases with silent bilateral infarcts on imaging. CONCLUSIONS: Contrary to observations from European and Asian populations, women were not at increased risk of incident AD in Rochester. Our findings, based on a medical records linkage system, corroborate findings from several other US studies that involved the direct contact of cohort members. The consistency of findings across study designs suggests that sex or sex-related exposures do not consistently play a major role in AD causation in American populations.

Incidence of vascular dementia in Rochester, Minn, 1985-1989.

OBJECTIVE: To examine the contribution of cerebrovascular disease to dementia. METHODS: We used the records-linkage system of the Rochester Epidemiology Project to ascertain incident cases of dementia in Rochester, Minn, for 1985 through 1989. We defined dementia using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. To define dementia types, we reviewed neuroimaging reports, which were available for two thirds of dementia cases, in addition to medical histories and neurologic examination results. Vascular dementia (VaD) was defined by 1 of the following criteria: dementia onset or worsening within 3 months of a clinical stroke or bilateral gray matter infarctlike lesions shown by imaging that fulfilled specified location criteria (critical imaging lesions). RESULTS: We found 482 incident cases of dementia. Overall, 10% of patients had onset or worsening of their dementia within 3 months of a stroke. Eleven percent of the incident dementia cases had bilateral gray matter lesions on imaging that were considered critical. Eighteen percent of patients had one or the other of these features (VaD by our criteria), but only 4% of patients had both. The incidence rate of VaD increased steeply with advancing age and was similar in men and women. Our incidence rates were similar to those from a recent European meta-analysis. CONCLUSION: The presence of either a stroke temporally related to dementia onset or worsening or of critical imaging lesions was common among dementia patients, whereas the occurrence of both features together was rare.