Factors affecting course and survival in Alzheimer's disease. A 9-year longitudinal study.

OBJECTIVE: To evaluate mean survival and to identify prognostic factors in a cohort of patients with Alzheimer's disease (AD). DESIGN: Multicentric 9-year cohort analytic study. SETTING: Seven neurology departments throughout Italy between April 1982 and January 1984. PATIENTS: We recruited a consecutive sample of 145 patients affected by probable AD (Multicenter Italian Study on Dementia protocol, National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). Five were misdiagnosed, and 21 could not participate in the longitudinal study. The clinicodemographic characteristics of the 119 enrolled patients (49 men, 70 women; mean age, 64.7 years; SD, 4.1 years; mean duration of disease, 3.1 years; SD, 1.8 years) did not differ from those of the 26 excluded patients. All underwent extensive cliniconeuropsychological testing every 6 months for at least 2 years until the patient died or our survey ended (April 30, 1991). Mean follow-up was 5.1 years (SD, 2.5 years). MAIN OUTCOME MEASURES: Death, severe functional impairment (a score > or = 17 on the Blessed Dementia Scale), and severe cognitive impairment (a score of < or = 7 on the Information-Memory-Concentration Test). RESULTS: Survival curves obtained by the Kaplan-Meier method indicated that (1) patients with early- and late-onset disease (ie, before or after age 65 years) showed no difference either in relative survival or in time to reach predetermined functional and cognitive end points; (2) severely aphasic patients became profoundly demented significantly sooner than those with mild to moderate aphasia (P < .0001). Among clinicodemographic variables analyzed by a Cox model, severe language disability and functional loss proved to be the best predictors of death independent of age at onset or degree of dementia. CONCLUSIONS: Age at onset did not influence course and survival in AD. Severe aphasia appears to be the best predictor of death and unfavorable course.

5HT2-receptors and serotonin release: their role in human platelet aggregation.

Involvement of 5HT2 receptors in human platelet aggregation was assessed by studying the effect of ADP, epinephrine and thrombin on 3H-5HT release from platelets. The release experiments were made with a perfusion method to preserve any compound, released or formed by platelet, from interacting with platelet itself. In these conditions, aggregation does not occur, as confirmed by Scanning Electron Microscopy. These release experiments showed that the platelet activation by such agents is coupled with 5-HT release. The aggregation experiments, made on different aliquots of the same platelet-rich plasma (PRP), showed that the released 5-HT, interacting with its own receptors on platelet activated surface, determines aggregation. In fact, although it is known that 5-HT added to PRP was only able to induce a moderate platelet aggregation, the 5-HT2 antagonist ketanserin counteracted the aggregation induced by ADP, epinephrine and thrombin. These results suggest that a 5HT2 antagonist could be therapeutically important in those pathological states in which serotonin, released by activated platelets, may increase aggregation.

Italian Multicentre Study on Dementia (SMID): a neuropsychological test battery for assessing Alzheimer's disease.

For the Italian Multicentre Study on Dementia, a longitudinal survey on Alzheimer's disease (AD) initiated in 1982, we developed a neuropsychological test battery for screening, staging and monitoring cognitive impairment in AD patients and for delineating their pattern of cognitive decline. The tests measured higher cortical functions primarily involved in AD, such as short- and long-term memory, orientation, language, and praxis, and spanned a large enough range of difficulty to minimize ceiling and floor effects. We administered this battery to 143 clinically diagnosed AD patients and 146 hospital controls whose scores were corrected for age and educational level. Interrater and test-retest reliability were substantial, as were content and concurrent validity. Five of the battery's subtests proved capable of accurately screening early demented from non-demented elderly subjects and of staging mild, moderate, severe and very severe mental impairment. The mean performance of subjects classified into these categories differed significantly on all cognitive functions tested. Follow-up studies are in progress.

Correlation between migraine and circulating platelet aggregates.

We studied platelet aggregates, by Wu and Hoak's technique, in 73 patients (49 F and 24 M), aged 14-61 (mean age 50.4 +/- 12.2) with migraine. Platelet aggregates were expressed as Platelet Aggregate Ratio (PAR). We consider as pathological PAR values lower than 86. Mean PAR value of migraine patients (78.3 +/- 8.68 SD) was significantly lower (p less than 0.001) than that of 90 control subjects (95.4 +/- 6.15 SD). Normal PAR values were found only in 27.4% of the migraine patients. The patients were divided according to the interval from the last attack: 17 patients were studied in the 1st week (PAR = 73.76 +/- 7.6 SD; 5.8% of the values in the normal range), 15 in the 2nd week (76.6 +/- 7.02 SD; 13.3% of the values in the normal range) and 41 between 15th and 30th day (80.78 +/- 8.78 SD; 29.6% of the patients in the normal range). The mean PAR value of the patients studied during the first week was significantly lower (p less than 0.01) than that of the patients studied between 15th and 30th day. No significant differences were found between the patients with classical, common and complicated migraine.