Objectives: We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease. Methods: A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline. Results: No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22

All patients attending the Clinic for Alzheimer Disease and Related Disorders have detailed family histories taken by a geneticist. To date, genetic histories are available for 446 consecutive, unrelated individuals. Of these, 151 (33.9%) are diagnosed as having "probable" (N = 141) or "autopsy-confirmed" (N = 10) Alzheimer disease according to recognized criteria. This data base represents a relatively unselected population with respect to more than one person in the family having dementia. Seventy-one of these 151 index cases (47.0%) have a positive family history of dementia, of which 8 (5.3%) may represent the familial (autosomal dominant) form of Alzheimer disease (FAD). Age-corrected empiric recurrence risks for Alzheimer disease/dementia were calculated for first-degree relatives of these 151 index cases using the Kaplan-Meier lifetable method.

Clinical differentiation between forms of progressive dementia can prove difficult, particularly when relatively rare forms of dementia are involved. Factors such as family history of dementia, age at onset, presenting features such as personality change, cognitive deficits, psychiatric symptoms, and clinical course (progressive deterioration; retention of skills over time) may prove useful for directing investigations to identify underlying pathology and genetic implications. This is illustrated by two patient reports. Each patient had the onset of memory/behavioral problems at approximately age 40 years, was initially given a psychiatric, non-dementing diagnosis, and had a positive family history for early onset behavioral and memory problems. After longitudinal assessment, the diagnosis of Alzheimer disease was confirmed at autopsy in one patient and a diagnosis of familial, adult-onset metachromatic leukodystrophy in the other. RESUME: Diagnostic differentiel de la leucodystrophie metachromatique de I'adulte et de la maladie d'Alzheimer familiale dans une clinique d'Alzheimer. II peut etre difficile de differencier cliniquement les formes progressives de demence, particulierement quand il s'agit de formes relativement rares. Des facteurs comme une histoire familiale de demence, l'age de debut, les manifestations initiales, telles les changements de personnalite, les deficits cognitifs, les symptomes psychiatriques, et 1'evolution clinique (la deterioration progressive, la preservation a travers 1'evolution de certaines habiletes) peuvent s'averer utiles pour orienter l'investigation dans le but d'identifier la pathologie sous-jacente et les implications genetiques. Nous rapportons deux cas qui illustrent ce fait. Les problemes de memoire/de comportement ont commence vers l'age de 40 ans chez chacun des deux patients, tous les deux ont reiju un diagnostic psychiatrique ne comportant pas de demence et avaient une histoire familiale positive de problemes precoces de comportement et de memoire. A la suite d'une evaluation longitudinale, le diagnostic de maladie d'Alzheimer a ete confirme a l'autopsie chez un patient et un diagnostique de leucodystrophie metachromatique de I'adulte chez I'autre.

Positron emission tomography (PET) has dramatically improved our ability to examine the functioning of the living brain. PET studies of neural pathways of the major sensory modalities--auditory, visual, somatosensory--have confirmed many traditional neuropsychological concepts, such as cross-lateral representation and regional functioning to particular primary sensory cortical areas. Other PET studies have used radioisotopes to examine relationships between radiopharmaceutical agents and neurobehavioral functioning in both normal and neuropathological states. In some areas, PET methodology requires further refinement. For example, effort should be made to develop the technology to do multiple scans within a short time frame; statistical procedures to examine relationships between neuropsychological tasks and the activity or presence of radiopharmaceutical agents in multiple sites; adequate controls for experimental error; and activation paradigms controlling the nonspecific effects of simple arousal. PET activation models of cognition suggest that a "systems efficiency" approach to assessing neuropsychological test performance involving both serial and parallel processing would be useful. These developments will improve empirical methodology and our understanding of brain-behavior relationships.