W. Gary Snow

The NINCDS‐ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease A clinicopathologic study of 57 cases

Neuropathologic confirmation is required to validate the NINCDS-ADRDA Work Group criteria for the clinical diagnosis of Alzheimers disease (AD). Neuropathologic inclusion and exclusion criteria for AD, however, are not uniform. The purpose of this investigation was to examine the confirmation rate for the Work Group criteria against differing neuropathologic criteria for AD. The sample consisted of 57 cases, 22 of which had received a clinical diagnosis of AD. Nine neuropathologic criteria for AD were applied in a blind fashion to each of the 57 cases. Our results indicated that, depending on the neuropathologic criteria applied, the clinicopathologic agreement ranged from 64% to 86%. These findings demonstrate the need for universally accepted neuropathologic and clinical criteria for AD.

Psychological, topographic EEG, and CT scan correlates of frontal lobe function in schizophrenia

This study examined frontal lobe function in a group of 20 patients with schizophrenia, on and off medication, compared to 20 normals matched for age, sex, handedness, intelligence, and educational level. Schizophrenic patients generally did not perform as well as normals on the Wisconsin Card Sorting Test (WCST). Patients off medication performed less well on this test than those on medication. Those on medication did not perform as well as those off medication on the design and word fluency tests, which suggested that medications may affect various aspects of frontal lobe function differently. During the WCST, normal subjects demonstrated an increase in beta mean frequency of the electroencephalogram in frontal and centrotemporal regions which was not statistically significant in either schizophrenic group. This shift in beta mean frequency was found to correlate positively with performance on the WCST in normals, but not in patients. Patients with more negative symptoms tended to show a smaller increase in beta mean frequency during the WCST. Performance on the WCST was correlated negatively with ventricle-brain ratio in all subjects, suggesting that frontal lobe function might be related to computed tomographic measures in the normal population as well as in schizophrenic patients. There was no correlation with performance on the WCST and length of illness.

A randomized double-blind trial of the effects of hormone therapy on delayed verbal recall in older women

We examined whether estradiol and norethindrone hormone therapy (HT) prevented decline in delayed verbal recall in older women with normal to mildly impaired memory functioning. This was a 2-year, randomized, double-blind, placebo-controlled trial of 142 women aged 61-87, randomly assigned to receive 1 mg 17-beta estradiol daily and 0.35 mg norethindrone 3 days/week or daily placebo for 2 years. The primary outcome was short-delay verbal recall of the California Verbal Learning Test (CVLT). To look for differences in response to HT by baseline short-delay recall, we examined the primary outcome in participants grouped according to whether their baseline scores were below average for the age group or greater than or equal to this score and according to whether they met criteria for Mild Cognitive Impairment (MCI) or not. 133 women completed 1 year of the trial and 128 completed 2 years. Prespecified covariates in all repeated measures analyses of covariance (RANCOVA) included age, education, APOE epsilon4, and prior HT use. RANCOVA showed no overall significant treatment effects at year 1 or year 2. After testing for an interaction, which was significant (p=0.02), we found that women in the HT group who scored at or above the average showed significantly less decline than the placebo group in short-delay verbal recall after 1 year, p=0.007 and 2 years, p=0.01. No treatment effects were found in women below the average in either year. When grouped according to whether the participant met criteria for MCI, the interaction between treatment group and MCI subgroup was not significant. These results suggest that benefits of estrogen exposure may be limited to those with average to above average scores on the delayed verbal recall. HT dose and formulation may have contributed to these beneficial outcomes. Replication is warranted before recommendations can be made in the clinical setting.

Use of the Rey Auditory Verbal Learning Test in Differentiating Normal Aging from Alzheimer's and Parkinson's Dementia.

Elderly control subjects (n = 38) performed better than did patients with moderate Alzheimers disease (AD; n = 18), severe AD (n = 33), or Parkinsons dementia (PD; n = 12) on all measures of the Rey Auditory Verbal Learning Test (RAVLT). The moderate-AD group performed better than did the severe-AD group on the 5 learning trials of List A. Unlike the controls and PD patients, both AD groups showed a greater recency than primacy effect, and both performed equally poorly on recall of List A after List B had been presented. The PD group showed poorer recall on List B than did the moderate-AD group but had better recognition scores than did both AD groups

Identification of Those at Greatest Risk of Harm Among Cognitively Impaired People Who Live Alone

Our purpose was to determine whether we could predict, from among seniors with cognitive impairment who lived alone, those at highest risk of experiencing harm or needing emergency services. Specifically, our focus was on the problems that occurred as a result of negligence due to cognitive impairment. We assessed 139 people, 65 years of age and older, who lived alone in a large urban centre and who showed cognitive impairment on a screening test. On average, participants were 83-year-olds, had 11 years of education, and a Mini-Mental State Score of 23. A total of 39% met diagnostic criteria for dementia. All underwent assessment of their neuropsychological abilities, behavioural characteristics and social supports. A study informant was identified for each participant who, together with the family physician, provided detailed information regarding the participants’ use of emergency medical, fire or police services, their experience of harm or loss of property over the last 12 months. We determined that negligence due to cognitive impairment caused harm or the need for emergency services based on informants’ and primary care physicians’ reports and by three independent raters. Logistic regression analyses indicated that the best predictors of harm or use of emergency services were male sex, self-care deficits, and poor performance on the Trail Making Test, Part B. The sensitivity of this three-variable regression model was 81% and the specificity was 66%. The likelihood ratio of both the positive and negative tests for harm represented a small but meaningful change in pretest to posttest probability of harm. These results indicate that we can estimate an individual’s probability of harm based on performance on these three variables. The next step is to confirm the findings with prospectively collected data.

An evaluation of the sensitivity of premorbid IQ estimators for detecting cognitive decline

Twenty-two studies were reviewed that estimated Wechsler Adult Intelligence Scale (WAIS/WAIS-R; D. Wechsler, 1981) IQs for normal individuals using demographic regression equation estimators and/or ability estimators such as the National Adult Reading Test. None of these studies originally reported the sensitivity of their method for detecting cognitive decline. The potential utility of each method was quantified by using psychometric theory to calculate the magnitude of cognitive decline that could be reliably detected. Results showed that for a cognitive decline in WAIS-R Verbal Scale IQ (VIQ) to be detected 80% of the time, the decline would have to be at least 25 VIQ points for demographic predictor methods, and at least 20 VIQ points for reading test predictor methods. Implications of the limited sensitivity of these methods for clinical applications are discussed and interpretation recommendations are provided.

A brief neuropsychological battery for the differential diagnosis of probable alzheimer's disease

Abstract The purpose of this study was to develop a brief battery of tests to distinguish patients with Alzheimers disease (AD) from normal controls and from patients with other dementias (OD). The sample included 35 AD patients and 35 OD patients (matched on mental status) and a normal control group (n = 108). All participants underwent a neuropsychological assessment and were rated on the London Psychogeriatric Rating Scale (LPRS). Logistic regression analyses (with backward stepping) accurately classified 94% of the normal controls and demented patients with a delayed recall test. The same test and the Disengagement Scale of the LPRS accurately classified 74% of the AD and OD patients. These findings were replicated with a second random assortment of AD and OD subjects matched again on mental status. These results indicate that if the purpose of the assessment is to distinguish AD from other dementias, these two tests may be most useful.