The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects. The protocol provides neuropathologic definitions of such terms as "definite Alzheimer's disease" (AD), "probable AD," "possible AD," and "normal brain" to indicate levels of diagnostic certainty, reduce subjective interpretation, and assure common language. To pretest the protocol, neuropathologists from 15 participating centers entered information on autopsy brains from 142 demented patients clinically diagnosed as probable AD and on eight nondemented patients. Eighty-four percent of the dementia cases fulfilled CERAD neuropathologic criteria for definite AD. As increasingly large numbers of prospectively studied dementia and control subjects are autopsied, the CERAD neuropathology protocol will help to refine diagnostic criteria, assess overlapping pathology, and lead to a better understanding of early subclinical changes of AD and normal aging.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease

Objective
The purpose of this paper is to provide a comprehensive review of information accumulated over the past 26 years regarding the psychometric properties and utility of the Mini-Mental State Examination (MMSE).

Participants
The reviewed studies assessed a wide variety of subjects, ranging from cognitively intact community residents to those with severe cognitive impairment associated with various types of dementing illnesses.

Main Outcome Measures
The validity of the MMSE was compared against a variety of gold standards, including DSM-III-R and NINCDS-ADRDA criteria, clinical diagnoses, Activities of Daily Living measures, and other tests that putatively identify and measure cognitive impairment.

Results
Reliability and construct validity were judged to be satisfactory. Measures of criterion validity showed high levels of sensitivity for moderate-to-severe cognitive impairment and lower levels for mild degrees of impairment. Content analyses revealed the MMSE was highly verbal, and not all items were equally sensitive to cognitive impairment. Items measuring language were judged to be relatively easy and lacked utility for identifying mild language deficits. Overall, MMSE scores were affected by age, education, and cultural background, but not gender.

Conclusions
In general, the MMSE fulfilled its original goal of providing a brief screening test that quantitatively assesses the severity of cognitive impairment and documents cognitive changes occurring over time. The MMSE should not, by itself, be used as a diagnostic tool to identify dementia. Suggestions for the clinical use of the MMSE are made.

The mini-mental state examination: a comprehensive review.

During the past two decades we have witnessed a rather impressive growth of theoretical innovations and conceptual revisions of epistemological and methodological approaches within constructivist‐qualitative quarters of the social sciences. Methodological discussions have commonly addressed a variety of methods for collecting and analyzing empirical material, yet the critical grounds upon which these were reformulated have rarely been extended to embrace sampling concepts and procedures. The latter have been overlooked, qualifying only as a ‘technical’ research stage. This article attends to snowball sampling via constructivist and feminist hermeneutics, suggesting that when viewed critically, this popular sampling method can generate a unique type of social knowledge—knowledge which is emergent, political and interactional. The article reflects upon researches about backpacker tourists and marginalized men, where snowball sampling was successfully employed in investigating these groups' organic social ne...

/pdf/sampling-knowledge-the-hermeneutics-of-snowball-sampling-in-26v42j7gh6.pdf

Sampling Knowledge: The Hermeneutics of Snowball Sampling in Qualitative Research

ContextPostmenopausal women have a greater risk than men of developing Alzheimer
disease, but studies of the effects of estrogen therapy on Alzheimer disease
have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin,
in the Women's Health Initiative (WHI) trial were discontinued because of
certain increased health risks in women receiving combined hormone therapy.ObjectiveTo evaluate the effect of estrogen plus progestin on the incidence of
dementia and mild cognitive impairment compared with placebo.Design, Setting, and ParticipantsThe Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind,
placebo-controlled clinical trial, began enrolling participants from the Women's
Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the
4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women
free of probable dementia, aged 65 years or older, and recruited from 39 of
40 WHI clinical centers were enrolled in the WHIMS.InterventionParticipants received either 1 daily tablet of 0.625 mg of conjugated
equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or
a matching placebo (n = 2303).Main Outcome MeasuresIncidence of probable dementia (primary outcome) and mild cognitive
impairment (secondary outcome) were identified through a structured clinical
assessment.ResultsThe mean (SD) time between the date of randomization into WHI and the
last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants
was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia,
40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the
placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence
interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P = .01). This increased risk would result in an additional 23 cases
of dementia per 10 000 women per year. Alzheimer disease was the most
common classification of dementia in both study groups. Treatment effects
on mild cognitive impairment did not differ between groups (HR, 1.07; 95%
CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P = .72).ConclusionsEstrogen plus progestin therapy increased the risk for probable dementia
in postmenopausal women aged 65 years or older. In addition, estrogen plus
progestin therapy did not prevent mild cognitive impairment in these women.
These findings, coupled with previously reported WHI data, support the conclusion
that the risks of estrogen plus progestin outweigh the benefits.

/pdf/estrogen-plus-progestin-and-the-incidence-of-dementia-and-4euuhiehjh.pdf

Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.

Background Mild cognitive impairment (MCI) is considered to be a transitional stage between aging and Alzheimer disease (AD). Objective To determine whether MCI represents early-stage AD by examining its natural history and neuropathologic basis. Design A prospective clinical and psychometric study of community-living elderly volunteers, both nondemented and minimally cognitively impaired, followed up for up to 9.5 years. Neuropathologic examinations were performed on participants who had undergone autopsy. Setting An AD research center. Participants All participants enrolled between July 1990 and June 1997 with Clinical Dementia Rating (CDR) scores of 0 (cognitively healthy; n = 177; mean age, 78.9 years) or 0.5 (equivalent to MCI; n = 277; mean age, 76.9 years). Based on the degree of clinical confidence that MCI represented dementia of the Alzheimer type (DAT), 3 subgroups of individuals with CDR scores of 0.5 were identified: CDR 0.5/DAT, CDR 0.5/incipient DAT, and CDR 0.5/uncertain dementia. Main Outcome Measure Progression to the stage of CDR 1, which characterizes mild definite DAT. Results Survival analysis showed that 100% of CDR 0.5/DAT participants progressed to greater dementia severity over a 9.5-year period. At 5 years, rates of progression to a score of CDR 1 (or greater) for DAT were 60.5% (95% confidence interval [CI], 50.2%-70.8%) for the CDR 0.5/DAT group, 35.7% (95% CI, 21.0%-50.3%) for the CDR 0.5/incipient DAT group, 19.9% (95% CI, 8.0%-31.8%) for the CDR 0.5/uncertain dementia group, and 6.8% (95% CI, 2.2%-11.3%) for CDR 0/controls. Progression to greater dementia severity correlated with degree of cognitive impairment at baseline. Twenty-four of the 25 participants with scores of CDR 0.5 had a neuropathologic dementing disorder, which was AD in 21 (84%). Conclusions Individuals currently characterized as having MCI progress steadily to greater stages of dementia severity at rates dependent on the level of cognitive impairment at entry and they almost always have the neuropathologic features of AD. We conclude that MCI generally represents early-stage AD.

https://www.cbsnews.com/htdocs/pdf/alzheimer.pdf

Mild cognitive impairment represents early-stage Alzheimer disease.

The Geriatric Depression Scale (GDS) exists in both short and long forms. The original 30-item form of the GDS has been shown to be an effective screening test for depression in a variety of settings. However, its utility in patients with dementia of the Alzheimer type (DAT) is questionable. The short, 15-item version of the GDS was developed primarily for brevity and, in particular, for use in populations such as the medically ill or those with dementia, where the longer form might be burdensome. How well this short form works in these populations, however, is largely undetermined. In this paper, the sensitivity and specificity of the 15- and 30-item GDS are compared in a group of patients who were either cognitively intact or had mild DAT. The findings suggest that the short version of the GDS, like its longer predecessor, is an effective screening tool in the cognitively intact. However, in a population of subjects with mild DAT, it does not appear to retain its validity.

The Short Form of the Geriatric Depression Scale: A Comparison With the 30-Item Form:

• There is a growing need for methods for measuring and staging the natural history of dementia of the Alzheimer type. One instrument, designed with that purpose in mind, is the Washington University Clinical Dementia Rating. We tested its reliability using multiple clinicians in a videotape-design study, and it proved reliable under these study conditions.

Reliability of the Washington University Clinical Dementia Rating.

Forty-three subjects with mild senile dementia of the Alzheimer type (SDAT, so-called probable Alzheimer's disease) were studied longitudinally by serial administration of several tests to rate dementia. Comparison was made with 58 healthy elderly controls. The clinical diagnosis was confirmed in all 16 autopsies. At 5 years after entry into the study, the cumulative rate of nursing home placement was 73%, and of death, 30%, rising at 7 years to 84% and 44%, respectively. Four of six clinical measures of dementia were found to correlate with the natural history of SDAT. Several measures are better than a single one in carrying out longitudinal studies of the disorder.

Mild senile dementia of the Alzheimer type: 2. Longitudinal assessment.

The Alzheimer Disease Research Center at Washington University's medical school has gathered a large sample of subjects with senile dementia of the Alzheimer type (SDAT) who are free of other potentially complicating medical, neurologic and psychiatric disorders. Using this homogeneous population, we have characterized psychotic symptoms associated with SDAT. Three groups of symptoms occur commonly: paranoid delusions, misidentification syndromes, and hallucinations. The nature and frequency of these syndromes are discussed.

The nature of psychotic symptoms in senile dementia of the Alzheimer type.

The frequency of symptoms of depression (Feighner criteria) was evaluated in subjects with dementia of the Alzheimer type (DAT) and matched controls enrolled in a longitudinal natural history study of DAT. Despite enrollment criteria which excluded subjects with affective disorders, the collateral sources of subjects with DAT described these subjects as having significantly more "depressive" symptoms than controls without dementia at entry, and at 15- and 34-month follow-up. The collateral sources of the subjects with DAT reported that these demented individuals experienced significantly greater loss of interest, decreased energy, difficulty in thinking and concentrating, and psychomotor agitation or retardation then did the control group. The subjects with DAT reported fewer symptoms than did their collateral sources, but like their collateral sources, they did not report a global elevation of all Feighner symptoms, but rather related significantly greater difficulty in thinking and concentrating than the controls and a tendency toward loss of interest and psychomotor changes. No subject became clinically depressed. The results suggest a significant overlap between the symptoms of dementia and depression. The frequency with which the above symptoms occur in DAT confounds the use of Feighner and, by extension, DSM-III criteria in diagnosing depression in cognitively impaired individuals with DAT.

William J. Burke

Papers

The Short Form of the Geriatric Depression Scale: A Comparison With the 30-Item Form:

Reliability of the Washington University Clinical Dementia Rating.

Mild senile dementia of the Alzheimer type: 2. Longitudinal assessment.

The nature of psychotic symptoms in senile dementia of the Alzheimer type.

Symptoms of "depression" in dementia of the Alzheimer type.