Neuropathological findings in patients with clinical diagnoses of probable Alzheimer's disease.

To assess prospectively the accuracy of standard antemortem clinical diagnostic criteria for Alzheimer's disease, post-mortem examinations were performed on 25 patients who had met DSM-III criteria for primary degenerative dementia and National Institute of Neurological and Communicative Disorders and Stroke criteria for probable Alzheimer's disease. Seventeen patients (68%) met neuropathological criteria for Alzheimer's disease. Two presenile-onset patients had diffuse neocortical senile plaques of insufficient number for definite Alzheimer's disease. Six patients had non-Alzheimer's disease diagnoses. Five of these six had presenile-onset dementia. These results suggest caution in the antemortem diagnosis of Alzheimer's disease in presenile-onset dementia.

TSH responses to two TRH doses in men with Alzheimer's disease.

TSH responses to two TRH doses (0.1 mg, 0.5 mg) were determined in 10 men with Alzheimer's disease (AD) and in nine healthy matched controls. Maximum change in TSH (delta TSH) and TSH responses over time, analyzed independently for each TRH dose, did not reveal any significant differences between the AD and the normal subjects. Blunted delta TSH responses were an uncommon finding in both groups. Analyses examining the influence of TRH dose on TSH responses revealed significant group differences. In normal subjects, delta TSH responses following the 0.5 mg TRH dose were significantly greater than delta TSH responses following the 0.1 mg TRH dose (p less than 0.01). However, in the AD group, the effects of TRH dose on delta TSH were largely attributable to the exaggerated and outlying TSH responses of one AD subject. For the remaining nine AD subjects, delta TSH responses following the 0.1 mg and 0.5 mg TRH doses were not significantly different (p greater than 0.1). In the analysis of TSH responses over time, the difference between the 0.1 mg and the 0.5 mg TRH-induced TSH responses was significantly smaller in the AD group at several timepoints after infusion compared to the normal subjects.

Pressor, norepinephrine, and pituitary responses to two TRH doses in Alzheimer's disease and normal older men.

Changes in blood pressure (BP), plasma norepinephrine (NE), serum prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) associated with infusions of two thyrotropin-releasing hormone (TRH) doses (0.1 mg, 0.5 mg) were examined in 10 men with early-onset Alzheimer's disease (AD) and nine normal matched controls. During the first 5 min after TRH infusion, significant increases from baseline in systolic BP (p less than 0.001), diastolic BP (p less than 0.001), and plasma NE (p less than 0.006) occurred in the study subjects. The magnitude of the BP and NE responses did not differ significantly as a function of TRH dose (p greater than 0.3). Diastolic pressor responses to TRH were substantially blunted in AD subjects relative to controls, after both the 0.1-mg (p less than 0.003) and 0.5-mg (p less than 0.02) doses. There were trends toward attenuated responses in the AD subjects for systolic BP (p less than 0.09) and plasma NE (p less than 0.07). Significant increments in serum PRL, LH, and FSH (all p less than 0.001) also occurred after TRH, but the magnitude of the hormone responses did not differ significantly between the AD and the normal subjects (p greater than 0.18). These results suggest the possibility that TRH-evoked activation of the sympathetic nervous system (SNS), as reflected by pressor and plasma NE responses, may be attenuated in men with early-onset AD.

Very low-dose neuroleptic treatment in two patients with agitation associated with Alzheimer's disease.

Two agitated patients with Alzheimer's disease who either failed to respond or worsened with conventional low-dose neuroleptic and other pharmacologic treatment are described. Both patients demonstrated sustained improvement with very low-dose neuroleptics, one with haloperidol 0.125 mg and the other with thioridazine 5 mg. Clinical, pharmacokinetic, and pharmacodynamic factors that may have accounted for this response are discussed.

Myoclonus, seizures, and paratonia in Alzheimer disease.

Twenty-eight patients with the clinical diagnosis of probable Alzheimer disease (AD) were followed longitudinally until death. The presence of myoclonus, seizures, and paratonia was monitored as part of this process. At autopsy, 22 of the patients met pathologic criteria for AD and 6 had other degenerative neurologic diseases. Myoclonus was present in 55% of the AD patients and none of the non-AD patients. Seizures were present in 64% of the AD patients, and only 17% of the non-AD patients. Paratonia was found frequently in all patient groups. In most patients, symptoms developed late in the course of their illness. The incidence of myoclonus, seizures, and paratonia in our patients was higher than in most previous studies. The reasons for this finding are discussed.