Depression symptoms before the onset of AD are associated with the development of AD, even in families where first depression symptoms occurred more than 25 years before the onset of AD. These data suggest that depression symptoms are a risk factor for later development of AD.

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Frontotemporal dementia is a rare form of progressive intellectual deterioration. Its most prominent clinical features are alterations in personality, motivation, and social conduct whereas memory and orientation remain largely unimpaired. Several underlying neurodegenerative processes may be distinguished which are confined to the cerebral cortex in most cases but occasionally involve the basal ganglia and rarely the anterior horn cells. Most frequently, histopathological examination reveals a non-specific loss of neurons accompanied by reactive gliosis. In a minority of cases, globose intraneuronal inclusions and achromatic ballooned neurons are seen. These peculiar morphological changes are called "Pick bodies" and "Pick cells" after the neurologist Arnold Pick who worked in Prague. It can be difficult to identify frontotemporal dementia because its major symptoms mimicnon-organic psychiatric disorders including mania, obsessive-compulsive disorder, schizophrenia, depression or personality disorder. Another problem of diagnosis is that all clinical instruments that are available for assessing cognition, activities of daily living, and non-cognitive symptoms have been tailored to the prototypic dementia in Alzheimer's disease and are less sensitive to the psychopathology of frontal lobe diseases. The burden that frontotemporal dementia imposes on caregivers is also completely different from the one encountered by families of patients with the more prevalent dementias. In the present contribution we summarize the current evidence on epidemiology, aetiology, and risk factors of frontotemporal dementia. Clinical symptoms and course will be illustrated by a case example. We will also provide guidelines for diagnosis and discuss treatment options.

Eighty-eight patients with mild to moderate dementia of the Alzheimer type were tested in a word list and a spatial pattern recall task. With increasing degree of dementia severity we found a decline in the initial recall scores while learning curves over five consecutive trials remained normal in the mildly demented patients. Furthermore, there was a loss of the primacy effect in the word list task in our moderately demented patients. These findings are consistent with the pattern that have been reported after medial temporal lobe dysfunction. The data are discussed in the framework of cognitive dual process theories of memory as indicators of a contextual retrieval deficit.