Background: The interpretation of neuropathological studies of dementia and Alzheimer’s disease is complicated by potential selection mechanisms that can drive whether or not a study participant is observed to undergo autopsy. Notwithstanding this, there appears to have been little emphasis placed on potential selection bias in published reports from population-based neuropathological studies of dementia. Methods: We provide an overview of methodological issues relating to the identification of and adjustment for selection bias. When information is available on factors that govern selection, inverse-probability weighting provides an analytic approach to adjust for selection bias. The weights help alleviate bias by serving to bridge differences between the population from which the observed data may be viewed as a representative sample and the target population, identified as being of scientific interest. Results: We illustrate the methods with data obtained from the Adult Changes in Thought study. Adjustment for potential selection bias yields substantially strengthened association between neuropathological measurements and risk of dementia. Conclusions: Armed with analytic techniques to adjust for selection bias and to ensure generalizability of results from population-based neuropathological studies, researchers should consider incorporating information related to selection into their data collection schemes.

To determine whether the presenilin 1 (PS1), presenilin 2 (PS2) and amyloid beta-protein precursor (APP) mutations linked to familial Alzheimer's disease (FAD) increase the extracellular concentration of amyloid beta-protein (A beta) ending at A beta 42(43) in vivo, we performed a blinded comparison of plasma A beta levels in carriers of these mutations and controls. A beta 1-42(43) was elevated in plasma from subjects with FAD-linked PS1 (P < 0.0001), PS2N1411 (P = 0.009), APPK670N,M671L (P < 0.0001), and APPV7171 (one subject) mutations. A beta ending at A beta 42(43) was also significantly elevated in fibroblast media from subjects with PS1 (P < 0.0001) or PS2 (P = 0.03) mutations. These findings indicate that the FAD-linked mutations may all cause Alzhelmer's disease by increasing the extracellular concentration of A beta 42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide.

In the medical and epidemiologic literature, a registry denotes a data base in which registrants share some common characteristic such as disease category. One criticism of registries is that they frequently collect subjects in a haphazard fashion and, hence, are “nonrepresentative of the population purportedly being represented.” In this report, we compare two registries: an incident-based Alzheimer's Disease Patient Registry (ADPR) recruiting subjects for epidemiologic studies from a large health maintenance organization; and an Alzheimer's Disease Research Center (ADRC) registry recruiting subjects for phenomenologic, biologic, and pharmacologic studies. While these registries share personnel, overlap geographically, and use similar diagnostic procedures, they differ substantially in their missions and resulting recruitment strategies. We compared these registries with respect to demographic characteristics and cognitive features at subject entry. Subjects enrolled in the incident-based registry are older and report shorter time between symptom onset and recruitment. They are less demented and mirror the general population demographically more closely than do subjects in the other registry. The ADRC registry contains a much greater proportion of subjects with higher educational attainment.

Although the cognitive and psychiatric symptoms associated with Alzheimer disease have received increasing attention over the past decade, the study of insight in this illness has been relatively neglected. This paper reports on the relationship between level of insight and severity of dementia in a large sample of patients with Alzheimer disease, largely with mild to moderately severe dementia. The study is based on data from 670 patients with a research diagnosis of probable Alzheimer disease who were enrolled in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The degree of insight was rated by the examiner on the basis of the patient's answers to questions probing awareness of his or her memory deficits or other symptoms of cognitive impairment. Severity of dementia was assessed using the Clinical Dementia Rating Scale, Short Blessed Test, Blessed Dementia Rating Scale, and Folstein Mini-Mental State Examination. Two-year longitudinal follow-up data on insight level and dementia severity were available for 148 of the 670 patients. Decreased level of insight correlated significantly with severity of dementia as measured by all rating instruments. For the patients followed for 2 years, 33.1% declined in level of insight from the entry level. This decline was statistically associated with more severe dementia as measured by the Blessed Dementia Rating Scale. This study confirms the generally accepted belief that patients with Alzheimer disease experience a progressive loss of insight as the severity of dementia increases. Due to methodologic limitations, we are unable to draw conclusions about loss of insight in patients with very mild cognitive impairment.

Journal of the American Geriatrics SocietyVolume 36, Issue 1 p. 82-83 Excess Disability in Demented Elderly Outpatients: The Rule of Halves Burton V. Reifler MD, MPH, Corresponding Author Burton V. Reifler MD, MPH Department of Behavioral Medicine, Bowman Gray School of Medicine at Wake Forest University.Department of Psychiatry and Behavioral Medicine, Bowman Gray School of Medicine, 300 S. Hawthorne Road, Winston-Salem, North Carolina, 27103.Search for more papers by this authorEric Larson MD, MPH, Eric Larson MD, MPH University of Washington, Seattle, WashingtonSearch for more papers by this author Burton V. Reifler MD, MPH, Corresponding Author Burton V. Reifler MD, MPH Department of Behavioral Medicine, Bowman Gray School of Medicine at Wake Forest University.Department of Psychiatry and Behavioral Medicine, Bowman Gray School of Medicine, 300 S. Hawthorne Road, Winston-Salem, North Carolina, 27103.Search for more papers by this authorEric Larson MD, MPH, Eric Larson MD, MPH University of Washington, Seattle, WashingtonSearch for more papers by this author First published: January 1988 https://doi.org/10.1111/j.1532-5415.1988.tb03440.xCitations: 28 Supported in part by NIMH grant #R01-MH33841. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume36, Issue1January 1988Pages 82-83 RelatedInformation

This retrospective review of medical records was designed to address three questions: 1) Can the depression seen in some patients with Dementia of the Alzheimer's Type (DAT) be successfully treated? 2) Does this treatment lead to any long‐term improvement in the patient's cognitive status? and 3) Do patients with coexisting DAT and depression have a different long‐term clinical course than nondepressed DAT patients? In the authors' sample of 131 DAT subjects, 41 (31%) also met DMS‐III criteria for a major affective disorder. Of those DAT plus depression patients whose records reflected treatment (usually with a tricyclic antidepressant), 85% (17 of 20) showed clear evidence of improvement in mood, vegetative signs, or activities of daily living (ADLs) based on review of the medical record. An analysis of change in cognitive function (measured by the Folstein Mini‐Mental State) and five global measures failed to reveal any differences between the depressed and nondepressed groups after a mean interval of 17 months. The depression that occurs in approximately one‐quarter to one‐third of DAT patients appears to respond to appropriate therapy. These patients often show improvement in their mood and ADLs but remain demented.