Interest in the health and diseases of elderly people has been growing in most parts of the world during the last few decades. One reason is that knowledge of normal aging and of the manifestations of disease in the higher age groups has been incomplete compared to the corresponding knowledge regarding other periods of human life. Another reason is the increasing absolute and relative number of elderly not only in the developed, but also importantly in the developing world. It is estimated, for example, that the increase of the population aged 80 and over from 1980 to 2020 will amount to 108% in the developed world compared to 377% in the developing world (U.N. Department of International Economic and Social Affairs, 1985).

The concept of dementia should not be used synonymously with the concept of organic mental disorders. By definition, according to DSM-III and ICD-10, dementia is a syndrome which includes memory impairment. The severity of the disorder is disabling and the course is chronic. Differential diagnosis includes age-associated memory impairment (AAMI), delirium, and depressive disorders. The dementias may be subdivided into four groups: idiopathic (primary degenerative dementias), vascular, secondary, and others. The idiopathic dementias are those in which etiology is assumed to be found within the brain itself. The main subgroup is Alzheimer-type dementia. The vascular dementias are those in which the blood supply to the brain is insufficient. Multi-infarct dementia (MID) is the prototype. In secondary dementias, somatic disorders either within or external to the brain cause the dementia.

Depression in old patients can be isolated or associated with dementia. In the first instance signs and symptoms sometimes mimic a demented state: disinterest, lack of initiative, mnesic complaints, slowing of thinking, learning difficulties. The EEG and the CT scan are useful in differential diagnosis, the value of the neuropsychological evaluation being compromised by lack of cooperation. In the second case the consequences of depression vary according to degree of severity of the dementia. In mild cases it can transitorily increase memory disturbances. In moderate and severe levels we see more regressive behavior. Sometimes we must wait for the therapeutic effects of antidepressant medication before we can establish the diagnosis with finality. The diagnosis of “pseudo-dementia” is only a provisional concept.

Clinical and neuropathological examinations have shown that Alzheimer's disease is not a single entity. An early onset form with predominant parietal symptoms (type I) can be differentiated from a late onset form with mainly general cognitive symptoms and only mild parietal symptoms (type II). In CSF of patients with Alzheimer's disease type I there are signs of reduced blood-CSF barrier function and the metabolites of serotonin and dopamine are reduced in early stages, while in patients with type II there is often a diminished blood-CSF barrier function and in later stages there are reduced monoamine metabolites. Studies of membrane lipids of the brain have shown that myelin lipids are reduced in type II while gangliosides are markedly reduced in type I. Based on this finding a method has been developed for the assay of gangliosides in CSF. An increase of ganglioside GM1 seems to be a hallmark for Alzheimer's disease, type I.

The limitations of establishing neuropsychological diagnosis through psychological testing and psychiatric examination by clinicians are discussed, along with the need to define cases of illness in a standardized way for research. The GMS-HAS-AGECAT package is a standardized assessment of mental state and historical information about onset of illness, from which data are used in a computer-assisted method to derive clinically based diagnoses of the principal types of dementia, depression and other mental illness. Recording is made of co-morbid states and levels of diagnostic confidence. Agreement between psychiatrists on AECAT diagnoses ranges from kappa values of 0.76 to 0.88, and validity has now been tested further by outcome studies. A short description is given of the Medical Research Council, EURODEM, World Health Organization and Pan American Health Organization studies now using this method.

Neuropsychology has an important role in a comprehensive psychogeriatric evaluation, especially in the assessment of dementia where the diagnosis is based on behavior. Current issues in the neuropsychology of aging and dementia in the oldest-old are discussed: the principal problem in the prevailing normative approach to discriminating between normal cognitive aging and pathology; the greater interindividual variability and, as a consequence, a need for subclassifications of individuals according to well-defined criteria; tests designed for cognitively impaired elderly and a contextual neuropsychological assessment procedure. Data from two ongoing Swedish studies of the oldest-old, illustrating some of these issues, are presented.

Positron Emission Tomography (PET) is a quantitative technique which can be used to measure regional values of cerebral metabolism, or uptake of radio-labeled tracers, in the living human. While structural scans (CT or MRI) may be normal in the degenerative dementias, or show generalized atrophy, functional imaging techniques allow differentiation of subtypes of dementias according to patterns of abnormal metabolism. This paper describes some of the variety of alterations in patterns of energy metabolism that may be observed in degenerative cognitive disorders and their correlations with clinical subtypes, together with an in vivo study of the dopaminergic system in subtypes of patients with dementia of the Alzheimer type (DAT).

Between January 1988 and December 1989, 1,600 autopsies were performed at Huddinge University Hospital, representing approximately 40% of the 4,000 deceased patients. In 40% (647) of the autopsy cases, patients showed clinical signs of CNS dysfunction.

Of these cases, 58% (380) were subject to neuropathological evaluation, including both macro- and microscopic examination. Only macroscopic examination by general pathologists was performed on the remaining cases. Clinical signs of dementia were seen in 10% (169 cases) of the autopsied patients. Neuropathological evaluations were performed on 70% (118) of these patients. Of these, 60% (70) showed degenerative changes and 36% (43) vascular alterations. Macroscopic examinations alone were performed in 30% of the cases. Of these, signs of severe cortical atrophy were seen in 21%, vascular lesions in 12%, and no macroscopic changes in 67%. The completeness of clinical and postmortem examinations of the 169 demented patients was variable. Approximately 40% of the patients lacked any diagnostic decision. In approximately 50% of the cases with diagnostic decision, the clinical diagnosis correlated with the histopathological diagnosis. This low correlation between the clinical diagnosis and the exact nature of the disease was primarily based on the variable completeness of the clinical examinations. In order to improve this situation, it is important to perform both a complete clinical investigation and a neuropathological verification of the nature of the disease.

A thorough neuropathological analysis of several hundred cases from a prospective dementia study shows degenerative disorders such as dementia of Alzheimer type (DAT) and frontal lobe dementia (FLD) of non-Alzheimer type to be the prevailing disorders.

The pattern of basic changes relatable to neuronal atrophy in DAT correlates better to functional parameters and symptomatology than do senile plaques and neurofibrillary tangle density and distribution. The etiological or pathogenetic role of amyloid and of a cholinergic deficit also remains unclear. The dominating disease pattern may be blurred by confounding additional alterations with more pronounced frontal case pathology, as found in a limited number of cases. Another and much more common factor is structural white matter attenuation associated with cerebrovascular pathology as well as frank infarctions in a smaller but still important number of DAT cases. The concurrence of degenerative and other brain changes each at subthreshold levels may cause signs and symptoms of a dementia difficult to classify.

Frontal lobe dementia of non-Alzheimer type, the next most common dementing degenerative disorder, displays only the basic changes found in DAT but derives its separate clinical profile from the frontal predominance of lesions. It may be confounded with Pick's disease and others possibly belonging to the same group, but also with frontally projected dementias due to lesions ranging from thalamic infarcts to brain stem afflictions.

The topographic pattern of lesions rather than the structural details forms a useful basis for a clinical classification of the dementing disorders.