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Half the patients with mild cognitive impairment (MCI) will develop dementia over a four-year period. The scientific literature was searched and analysed for predictors of rapid decline (MCI-plus) in patients with MCI. The most important predictors of fast cognitive deterioration were found to be: old age, previous rapid decline, severity and multiplicity of cognitive deficits, somatic co-morbidity, vascular and Alzheimer-type changes in the brain, Alzheimer-type cerebrospinal fluid findings and apolipoprotein E4 polymorphism. Many patients with MCI suffer from anxiety, depression or apathy and subtle, but subjectively significant, difficulties in the activities of daily living. It is concluded that MCI-plus offers a window for medical and psychological prophylaxis and rehabilitation.

The aim of the study was to examine the relationship of head circumference as a marker of maximal attained brain size to late-life cognitive impairment and dementia.Cognitive performance was assessed and the presence of dementia was diagnosed in a cross-sectional study of 442 Catholic sisters aged 65 years and over.A head circumference below average was significantly associated with the presence of dementia even after adjustment for age, body mass index and presence of one or two apolipoprotein E epsilon4 alleles (OR = 2.0; 95% CI: 1.1-3.6). The combination of small head circumference and apolipoprotein E epsilon4 strongly increased the risk of dementia (OR = 3.59; 95% CI: 1.44-8.97).The findings support the hypothesis that a larger head size reduces the risk of cognitive decline and dementia in old age.

Most neuropsychiatric disorders have a complex aetiology. Discovery of the underlying genetics will provide insights into the disorders and allow the subsequent development of therapeutic interventions based upon an understanding of causality. The first vulnerability genes in Alzheimer's disease (AD) have been identified. The contribution of each vulnerability gene to the disorder is limited and does not enable prediction of course and onset in individual cases, only modification of the a priori risk. However, people may wish to be informed about this modification. Professionals have not favoured this form of predictive testing due to an awareness of its limitations and its potential for harm. However, little is known about public attitudes and understanding of such genetic testing in neuropsychiatric disorders. The aim of our study was to assess the attitudes of the general population and to explore the influence on these attitudes of knowledge about the illness and the understanding of risk information. In our study, a representative sample of the German general population (n=2001), relatives of patients with Alzheimer's disease (n=101) and physicians (n=43) were interviewed about their attitudes towards genetic tests for Alzheimer's disease and their perception and interpretation of risk information. To assess the influence of genetic counselling on these factors, 234 people were questioned before, and four weeks after, they were provided with detailed relevant information. Our results indicate that a substantial proportion of the German population (57%) is in favour of psychiatric genetic testing for AD in general. Even when the explanatory power of a genetic test is limited, a substantial proportion of the population (47%) expressed an interest in genetic testing. Counselling slightly decreased the interest in having a genetic test for oneself (from 47% to 38%). Physicians were more hesitant than both relatives and the general population concerning predictive genetic testing. Only a minority (11%) favoured prenatal genetic testing. Our results also show that both knowledge about AD and the capacity to interpret risk estimates are limited. While physicians' estimation of their personal risk for developing AD approximated to the actual average risk for the population, people in the general population and the relatives of AD patients tended to overestimate their personal risk. However, most of the general population still perceived this risk as average or low. While most physicians could correctly interpret information regarding the probability of risk, only one third of AD patients' relatives or members of the general population could. As the decision of an individual to undergo predictive testing relies mainly on his understanding of risk, the ability to correctly interpret risk information will be of crucial importance in the future. From a medical perspective, the prevailing approach of professional associations to genetic testing appears reasonable and therefore should not be changed at present.

The frequency of dementia in very old subjects, the risk factors and the consequences of the disease were investigated in the Berlin Aging Study in an age- and gender-stratified design (ages 70-103 years, n = 516). Psychiatrists diagnosed a dementia syndrome according to DSM-III-R, applying the GMS-A and HAS interviews. The dementia frequency steeply increases until the 90-94 year group, but there is no further exponential increase for the 95+ group--instead for men the data show a plateau of dementia prevalence. Low education level turned out to be a risk factor, which explains the gender effect in a logistic regression analysis. The apolipoprotein E4 genotype was confirmed as a risk factor--however, only for the older subjects (85+). Dementia was a major reason for institutionalization. The 2-year mortality was no higher in dementia than for age-matched non-demented controls. The results gave a detailed picture of dementia in the very old. This is a prerequisite for planning facilities for psychiatric diagnostics and therapy as well as nursing care.

This paper focuses on the review of risk factors of Alzheimer's disease (AD). Despite the vast literature on AD only advanced age and genetic predisposition have been known factors in the development of this disease. Recent data estimate a point prevalence of 3% in the age group from 65-69 and a steady increase to 24% after the age of 85 and older. The allele ApoE4 on chromosome 19 is liked to the sporadic form of AD with late onset, although not disease-specific. The risk factor is increasing from 20 to 90% with the growing number of ApoE4-allele. Since the sporadic form of AD is diagnosed much more frequently and about 40% of the cases are ApoE4-negative, one should not overestimate the percentage of AD in patients with a genetic component. No gender differences have been established in view of education, social factors and higher life expectancy of women. Mental and physical activities seem to improve coping strategies and develop reserve capacities. The lack of education presents a risk factor as opposed to at least 6 years of elementary schooling. Various studies report an association of AD with head injuries. Depression, which is diagnosed 3 times more often prior to the onset of AD, may be part of a prodromal stage preceding the actual symptoms by several years. Thus, conclusions should be drawn with caution. No increased risk with nicotine and alcohol has been found. However, maternal age, exposure to aluminum, estrogen deficiency and various diseases have been controversially discussed.

A total of 30 patients with clinically diagnosed Alzheimer's disease and 55 healthy, age-approximated controls were followed up over a 2-year period to compare the course of functional and cognitive impairment, quantitative morphological and functional brain changes. No remarkable changes were observed within the control group in any of these modalities. There were significant differences between patients and controls at the first examination: Mini-Mental State Examination (MMSE), 16.1 +/- 7.3 compared with 28.7 +/- 1.4; left lateral ventricle 2.7 +/- 1.1% versus 1.6 +/- 0.7% of the total intracranial volume; right lateral ventricle 2.7 +/- 1.4% versus 1.4 +/- 0.4%; absolute delta-power 1.1 +/- 0.3 versus 0.9 +/- 0.2 microV2; and absolute theta-power 1.1 +/- 0.3 versus 0.8 +/- 0.2 microV2 (means +/- standard deviation). In the patient group, scores on the Blessed dementia rating scale deteriorated from 10.6 +/- 6.1 to 17.9 +/- 9.6; the MMSE decreased by 8.0 +/- 3.7; the left lateral ventricle volume increased by 0.9 +/- 0.7%, the right by 0.9 +/- 0.7% of the total intracranial volume; absolute delta-power increased by 0.2 +/- 0.4 microV2 and theta-power by 0.1 +/- 0.3 microV2. We could not confirm a relationship between age, age at onset or apolipoprotein E4 gene dose and the rate of clinical change. High initial Blessed dementia scores were correlated with more severe ventricular enlargement, and delta-theta increase during the follow-up period. High initial theta-power predicted more severe functional and cognitive deterioration. To our knowledge, this is the first longitudinal study reporting quantitative clinical, morphological and EEG-changes measured in two points in time in patients and non-demented controls.

The relevance of the apolipoprotein E epsilon 4 allele as risk factor for Alzheimer's disease is independent of age. This was demonstrated in 126 patients and 72 healthy controls. The age in both groups varied between 44 and 95 years. An earlier onset of symptoms among carriers of the epsilon 4 allele, however, was observed only in the oldest patients. This may reflect a selection bias which is due to the association of the epsilon 4 allele with two competitive age-dependent risks: for Alzheimer's disease and for coronary heart disease. In a subsample of 64 patients who had participated in a longitudinal study no relationship was found between the apolipoprotein E genotype and clinical symptoms or symptom progression.

The apolipoprotein E genotype was determined in 50 patients with clinically diagnosed and prospectively confirmed Alzheimer's disease of mild to moderate severity and in 50 healthy age- and sex-matched controls. The frequency of the epsilon 4 allele was increased in the patients irrespective of the age at onset and of a possible familial transmission of the disease. It was associated with a relative risk of 2.97. In patients who experienced first symptoms after the age of 65 years there was an inverse correlation between the number of epsilon 4 alleles and age at onset. The results suggest that in the absence of amyloid precursor protein mutations and of a gene which has not yet been precisely localized on chromosome 14, apolipoprotein E is involved in the pathogenesis of Alzheimer's disease. It probably exerts its influence by an acceleration or retardation of amyloid formation and/or tau hyperphosphorylation.