Michael Serby

Hypersensitivity to scopolamine in the elderly

Scopolamine hydrobromide, 0.43 mg/70 kg, was administered by subcutaneous injection to ten young and ten elderly subjects. A comprehensive neuropsychological test battery was used to assess the effects of scopolamine, as compared to placebo, on cognitive function. As previously reported for this group of young subjects, scopolamine significantly impaired performance on tests of recent memory and visuospatial praxis. The same effects were observed in the elderly subjects, but the magnitude of the effects was much larger. The scopolamine injections produced significant psychomotor slowing in the elderly, whereas higher doses of the drug are required to produce this effect in young subjects. In both young and old subjects scopolamine failed to affect immediate memory, language function, object sorting, and the frequency of intrusion errors (although trends toward an effect were more apparent in the elderly). Remote memory, tested in the elderly only, was also unaffected. The results suggest that scopolamines cognitive effects are quantitatively more pronounced in elderly subjects than young subjects, but that they are qualitatively similar and do not constitute a valid model for the cognitive dysfunction associated with Alzheimers disease.

Scopolamine effects on memory, language, visuospatial praxis and psychomotor speed

Scopolamine hydrobromide was administered by subcutaneous injection to 30 young subjects in a dose of 0.22 mg/70 kg, 0.43 mg/70 kg, or 0.65 mg/70 kg. Treatment effects were compared to placebo on an extensive cognitive assessment battery. Almost all tests in the battery had been previously administered to Alzheimers disease patients and nondemented elderly subjects. Scopolamine produced deficits on tests of verbal recall, visuospatial recall, visual recognition memory, visuospatial praxis, visuoperceptual function, and psychomotor speed. Immediate memory, language function, object sorting, and frequency of intrusion errors were unaffected. The low dose of scopolamine produced some peripheral anticholinergic signs but did not affect the cognitive measures. The results support the conclusion reached in previous studies that the cognitive profile of scopolamine-injected young subjects is more similar to that of the nondemented elderly than to that of Alzheimers disease patients.

CSF somatostatin in Alzheimer's disease

Studies have previously demonstrated low somatostatin levels in autopsy cortical tissue from Alzheimers disease (AD) patients and low somatostatin levels in CSF obtained from subjects with dementia. We evaluated levels of this peptide in 21 non-depressed subjects, 10 with AD, 2 with Parkinsons disease (PD), and 9 with other neurological conditions. The AD patients had significantly lower mean CSF somatostatin than the other neurological patients (14.6 +/- 1.5 S.E.M. versus 26.7 +/- 3.2 pg/ml, p less than 0.005). A demented PD subject had a level in the range of the AD group, while the non-demented PD patient had a value above this range. Thus, all 11 patients with AD or PD dementia, analogous disorders, had levels below 21.8 mg/ml, while 7 of the 10 remaining patients had values above 21.8 pg/ml. Age did not explain this finding.

Olfaction and Alzheimer's disease

Disturbances in the sense of smell may be important both clinically and theoretically in Alzheimers disease. Initial evidence of poor olfactory recognition performance in Alzheimers and parkinsonian dementias was followed by two reports which corroborated olfactory dysfunction in Alzheimers disease. The neuroanatomical and neurochemical bases for this disturbance are discussed. Despite an abundance of preclinical and clinical data linking olfaction with acetylcholine, a preliminary study failed to show any effect of scopolamine on olfactory thresholds. Two of the olfaction-Alzheimers studies found significantly better performance in other demented groups (alcoholics and patients with vascular dementia), suggesting possible utility in the differential diagnostic workup. The effect of aging per se on olfactory performance cannot be assessed without rigorous control for cognitive dysfunction in sampled populations.

Naltrexone and Alzheimer's disease

Naltrexone, an oral opiate antagonist, was administered to nine patients with a diagnosis of Alzheimers-type dementia (ATD) in a two-phase design: an open dose-ranging phase and a double-blind placebo-controlled trial for patients who showed improvement during the open phase. After a three day placebo (baseline) period, patients received increasing doses of naltrexone over two weeks up to a maximum daily dose of 100 mg. Assessments were made at baseline and at daily dose of 5 mg, 50 mg and 100 mg. Testing was done 2 to 4 hours after medication was administered. Any patient who showed cognitive/behavioral improvement on a given dose of naltrexone was then treated with this dosage in a double-blind crossover comparison to placebo. Criteria for inclusion in the double-blind phase consisted of improvement on three behavioral scales and at least one cognitive test on a given dose of naltrexone. Each double-blind phase followed a one-week washout and was two weeks long. Two of the nine patients demonstrated apparent cognitive enhancement on 100 mg daily of naltrexone and were then tested in the double-blind crossover period. Only one of these patients improved during active naltrexone administration. We conclude that the opiate antagonist naltrexone in a dosage range of 5-100 mg daily is not efficacious in ATD.

Olfactory deficits in AD: what we know about the nose

Abstract Roberts “zeolite hypothesis” of Alzheimers disease rests in part on evidence of olfactory deficits in this disorder. This commentary reviews this evidence and selected evidence for deficits in related disorders and normal aging, stressing gaps in knowledge and problems in assessment. We conclude that olfactory identification is most likely impaired in AD, but that other olfactory functions are poorly characterized at present.

Neuroleptic Malignant Syndrome in Alzheimer's Disease

Neuroleptic malignant syndrome (NMS) has been the subject of discussion in a number of recent literature reviews 1,2 ; a natural outcome due to the increasing awareness of this potentially lethal disorder. Reviews and case reports suggest that youth is a predisposing factor 1,2 ; there is no case report over 61 years of age. Although organic brain syndrome is cited as a risk factor, there is no documentation to support this. Recently, I treated an episode of NMS in a 65 year old man with Alzheimers disease (AD). This case brought into focus certain issues relevant to the management of patients with AD.

REM Sleep and Senile Dementia

To the Editor:-In the article on sleep and waking EEG, in dementia,’ Prinz and associates describe polygraphic changes which are indicative of senile dementia of Alzheimer’s type (SDAT). It should be noted that similar results were obtained in 1966 by Suzuki,2 who evaluated sleep EEG patterns of presenile and senile dementias. Suzuki compared Pick’s disease and cerebral arteriosclerosis to both presenile and senile forms of Alzheimer’s disease. In the presenile and senile patients with Alzheimer’s disease, there was shortening of REM sleep, which worsened with degree of dementia, and “variability-instability” of the REM stage in both mild and severe cases. Neither Pick’s disease nor cerebral arteriosclerosis was associated with these changes. Suzuki also postulated a brainstem locus of these abnormalities. The REM findings are of particular interest because of their support of the cholinergic hypothesis of Alzheimer’s d i ~ e a s e . ~ Cholinergic agents stabilize the REM state, whereas anticholinergics destabilize its4 Unstable and diminished REM sleep, then, is probably reflective of the decreased acetylcholine function that exists in Alzheimer’s disease. Thus, the measurement of REM sleep may prove to be a valuable yardstick in the assessment of therapeutic strategies in this disorder.