Jason Brandt

The hopkins verbal learning test: Development of a new memory test with six equivalent forms

Abstract A new test of verbal learning and memory, the Hopkins Verbal Learning Test, was developed. The test consists of three trials of free-recall of a 12-item, semantically categorized list, followed by yes/no recognition. Six parallel forms yielded equivalent results in normals. The performance of patients with Alzheimers disease and chronic amnesia is described. The test is likely to be useful in patients too impaired for more comprehensive memory assessments and where repeated testing is necessary.

Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls

BACKGROUND Up to 25% of adolescent girls in the USA are iron deficient. This double-blind, placebo-controlled clinical trial assessed the effects of iron supplementation on cognitive function in adolescent girls with non-anaemic iron deficiency. METHODS 716 girls who enrolled at four Baltimore high schools were screened for non-anaemic iron deficiency (serum ferritin < or = 12 micrograms/L with normal haemoglobin). 98 (13.7%) girls had non-anaemic iron deficiency of whom 81 were enrolled in the trial. Participants were randomly assigned oral ferrous sulphate (650 mg twice daily) or placebo for 8 weeks. The effect of iron treatment was assessed by questionnaires and haematological and cognitive tests, which were done before treatment started and repeated after the intervention. We used four tests of attention and memory to measure cognitive functioning. Intention-to-treat and per-protocol analyses were done. FINDINGS Of the 81 enrolled girls with non-anaemic iron deficiency, 78 (96%) completed the study (39 in each group). Five girls (three control, two treatment) developed anaemia during the intervention and were excluded from the analyses. Thus, 73 girls were included in the per-protocol analysis. Ethnic distribution, mean age, serum ferritin concentrations, haemoglobin concentrations, and cognitive test scores of the groups did not differ significantly at baseline. Postintervention haematological measures of iron status were significantly improved in the treatment group (serum ferritin 27.3 vs 12.1 micrograms/L, p < 0.001). Regression analysis showed that girls who received iron performed better on a test of verbal learning and memory than girls in the control group (p < 0.02). INTERPRETATION In this urban population of non-anaemic iron-deficient adolescent girls, iron supplementation improved verbal learning and memory.

Nonsteroidal anti-inflammatory drugs in Alzheimer's disease

Article abstract-We reviewed the records of 210 patients in the Johns Hopkins Alzheimers Disease Research Center to evaluate the role of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical features and progression of the disease. We compared patients taking NSAIDs or aspirin on a daily basis (N = 32) to non-NSAID patients (N = 177) on clinical, cognitive, and psychiatric measures. The NSAID group had a significantly shorter duration of illness at study entry. Even after controlling for this difference, the NSAID group performed better on the Mini-Mental State Examination, Boston Naming Test, and the delayed condition of the Benton Visual Retention Test. Furthermore, analysis of longitudinal changes over 1 year revealed less decline among NSAID patients than among non-NSAID patients on measures of verbal fluency, spatial recognition, and orientation. These findings support other recent studies suggesting that NSAIDs may serve a protective role in Alzheimers disease. NEUROLOGY 1995;45: 51-55

Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib.

BACKGROUND Observational studies have shown reduced risk of Alzheimer dementia in users of nonsteroidal anti-inflammatory drugs. OBJECTIVE To evaluate the effects of naproxen sodium and celecoxib on cognitive function in older adults. DESIGN Randomized, double-masked chemoprevention trial. SETTING Six US memory clinics. PARTICIPANTS Men and women aged 70 years and older with a family history of Alzheimer disease; 2117 of 2528 enrolled had follow-up cognitive assessment. INTERVENTIONS Celecoxib (200 mg twice daily), naproxen sodium (220 mg twice daily), or placebo, randomly allocated in a ratio of 1:1:1.5, respectively. MAIN OUTCOME MEASURES Seven tests of cognitive function and a global summary score measured annually. RESULTS Longitudinal analyses showed lower global summary scores over time for naproxen compared with placebo (- 0.05 SDs; P = .02) and lower scores on the Modified Mini-Mental State Examination over time for both treatment groups compared with placebo (- 0.33 points for celecoxib [P = .04] and - 0.36 points for naproxen [P = .02]). Restriction of analyses to measures collected from persons without dementia attenuated the treatment group differences. Analyses limited to measures obtained while participants were being issued study drugs produced results similar to the intention-to-treat analyses. CONCLUSIONS Use of naproxen or celecoxib did not improve cognitive function. There was weak evidence for a detrimental effect of naproxen.

Quality of life in dementia patients in long-term care.

To evaluate variables associated with quality of life (QOL) in dementia residents in a long‐term care facility using a recently standardized and validated dementia‐specific QOL scale (ADRQL).

Extended results of the Alzheimer’s disease anti-inflammatory prevention trial

Epidemiologic evidence suggests that nonsteroidal anti‐inflammatory drugs (NSAIDs) delay onset of Alzheimers dementia (AD), but randomized trials show no benefit from NSAIDs in patients with symptomatic AD. The Alzheimers Disease Anti‐inflammatory Prevention Trial (ADAPT) randomized 2528 elderly persons to naproxen or celecoxib versus placebo for 2 years (standard deviation = 11 months) before treatments were terminated. During the treatment interval, 32 cases of AD revealed increased rates in both NSAID‐assigned groups.

Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease Prospective analyses from the Predictors Study

Objective: To examine whether either extrapyramidal signs or psychotic features are associated with more rapid progression of Alzheimers disease. Background: It has been unclear whether extrapyramidal signs and psychosis are predictors of faster course or are simply late signs. Methods: Two hundred thirty-six patients with mild Alzheimers disease were recruited in three cities and followed semiannually. Results: Using Cox proportional hazards models that adjusted for age, sex, disease severity, and estimated duration of illness at study entry, the presence of extrapyramidal signs at entry was associated with higher relative risk (RR) of reaching moderate cognitive (RR = 2.35, 95% CI = 1.12 to 4.92) or functional (RR = 2.31, 95% CI = 1.37 to 3.90) severity, nursing home entry (RR = 2.51, 95% CI = 1.32 to 4.76), or death (RR = 3.04, 95% CI = 1.31 to 7.05). Psychosis predicted only the functional end point (RR = 1.85, 95% CI = 1.18 to 2.90). Using regression models, modified Mini-Mental State scores declined 1.30 points (95% CI = 0.16 to 2.44) per 6-month interval, more among patients with than those without extrapyramidal signs; patients with psychosis declined 1.15 (95% CI = 0.52 to 1.77) more mMMS points per interval. Conclusions: This study confirms extrapyramidal signs and psychosis as robust predictors of disease end points and rapid progression in Alzheimers disease.

Paralimbic frontal lobe hypometabolism in depression associated with Huntington's disease.

We measured regional cerebral glucose metabolism using 2-[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography in depressed and nondepressed patients with early Huntingtons disease (HD), compared with appropriately matched controls. Caudate, putamen, and cingulate metabolism was significantly lower in patients with HD than in control subjects, independent of mood state. Orbital frontal-inferior prefrontal cortex hypometabolism, however, differentiated depressed patients from both nondepressed patients and normal controls. These findings implicate selective dysfunction of the paralimbic regions of the frontal lobes in the mood disorder of HD. The metabolic pattern is similar to that in depression associated with Parkinsons disease, suggesting that the integrity of pathways linking paralimbic frontal cortex and the basal ganglia may be integral to the normal regulation of mood.

Quality of Life in Patients with Alzheimer's Disease as Reported by Patient Proxies

OBJECTIVE: To measure behaviors indicative of quality of life (QOL) in patients with Alzheimers disease and to examine correlates of patient QOL.

Clinical assessment of irritability, aggression, and apathy in Huntington and Alzheimer disease.

Thirty-one patients with Alzheimer disease (AD) and 26 patients with Huntington disease (HD) were assessed using new scales to measure apathy and irritability. An existing scale was used to assess aggression. A similar prevalence of apathy and irritability was found in the two groups. The HD patients were more aggressive than the AD patients. In a subsample of the two groups, matched for degree of cognitive impairment, the HD patients were found to be more apathetic than the AD group. Irritability was related to be the premorbid trait of “bad temper” in HD but not in AD. There was no interrelationship among the three symptoms in either group. The scales for irritability and apathy have both interrater and test-retest reliability. They are able to differentiate patients with AD and HD from normal, disease-free control subjects. The usefulness of these scales, in relation to preexisting scales, is discussed.