Secondary Dementias and Prevention

By secondary dementias we mean those pathological conditions in which the more or less important change in the cognitive functions represents only one of the manifestations of the clinical picture. Unlike in degenerative forms, in these forms very clear causal factors are identifiable. From the epidemiological point of view the vascular dementias constitute the most representative group, given that, together with Alzheimer’s Disease (AD), they account for around 90% of all forms of dementia.

The physiopathological basis of this nosographic group lies in cerebral damage to its physiopathological base. The use of neuroimaging techniques has become of fundamental importance in diagnosing these forms of dementia, given the fact that not all results of cerebral vascularisation are clinically apparent.

Another group of dementias includes forms which, compared to what occurs in the general population, appear with greater frequency in the course of SNC degenerative diseases such as Parkinson’s disease, Huntingdon’s chorea, progressive supra nuclear paralysis. In these cases the cognitive disorders, which often present distinctive characteristics, are an important sign in terms of prognosis.

A third grouping is made up of endocrine and metabolic dementias, caused by secondary encephalopathies due to malfunctions of these systems or to chronic organ insufficiency (renal, cardiac, pulmonary, hepatic). These present common characteristics, namely attention and vigilance disorders, inertia, apathy, psychomotor and ideational slowing. In some cases there can be psychiatric manifestations (delirium, hallucinations, depression, personality changes), as well as neurological signs and symptoms (convulsions, ataxia, dysarthria, paraesthesias, cephalalgies).

The secondary hypothyroidism forms deserve particular attention as they occur frequently in the elderly and are often unrecognised. In all these forms the cognitive disorder may not be completely reversible if treatment isn’t introduced very early. Some forms are currently of particular interest because of their relationships to stress and reproductive activity. These are the forms of endocrine dementia linked to an excessive activity of the hypothalamic-pituitary-adrenocortical axis (with hypercortisolism) and to a reduced or absent activity of the hypothalamic-pituitary-ovaric axis (with hypoestrogenism), such as in the post-menopausal phase.

If in the area of deficiency dementias Wernicke-Korsakoff syndrome has its clear nosographic arrangement, the same cannot be said of the dementia associated with alcoholism (‘alcoholic dementia’). Some authors in fact deny this is a specific dementia given the absence of an anatomical-pathological characterisation.

The interpretation can be further complicated by the frequent presence of encephalopathy marked by manifestations of hepatic insufficiency. The lack of folates, and particularly of vitamin B2, besides neurological appearances, can also lead to important cognitive alterations. In some cases disorders of the higher functions can appear even in the absence of other neurological signs or of anaemia. the toxic agents group of dementias includes those relating to lead, arsenic, manganese, and aluminium.

This last is considered the aetiological agent of dialysis dementia, less frequent today. Besides intellective decline it is also characterised by dysarthria, myoclonias and convulsions. Other industrial use substances, such as pesticides and solvents can cause a, sometimes, irreversible intellectual deterioration. Drug induced dementias are forms of cognitive deterioration linked to the excessive or inappropriate use of numerous pharmacological agents (benzodiazepines, anticholinergics, cortisonics, antihystemines, L-DOPA and agonists, diuretics, antihypertensives) particularly capable of altering attention, state of vigilance and, in some cases, memory. Barbiturates deserve to be mentioned separately, both because their use is often protracted and because their action mechanism seems to interfere with the excitability threshold of some synaptic populations.

Particular attention finally is given to pharmacological associations, often uncontrolled, ever more frequently found among the elderly. Secondary cerebral neoplasia dementias are those forms caused by benign or malignant, primitive or secondary expansive endocranic processes. Some symptoms are directly connected to the location of the tumour, while others, such as attention disorder, can be caused by cerebral oedema or the presence of hydrocephalus. Generally speaking slow growing tumours are more likely to pose differential diagnostic problems with dementia progressing on a degenerative basis.

It should be stressed how progress in neuroradiology has permitted earlier diagnosis of cerebral tumours, before they reach such dimensions as to form a situation of widespread cognitive deterioration. Included in the area of this group of dementias there are also those of a paraneoplastic nature, such as for example the so-called limbic encephalitis (with a deterioration of the memory and with behavioural symptoms), observed more frequently in association with lung carcinoma, and also occasionally those of the breast. Normotense hydrocephalus dementia forms part of a clinical picture characterised by movement disorders (which represent the most consistent and earliest sign) and sphincteric incontinence (later and sometimes inconsistent). Cognitive deterioration is neither particularly early, or serious. Its evolution is slow. It is often of a fluctuating type, and presents some traits typical of the frontal syndrome: the patient appears to be in slow motion, lacking initiative, and fails in attention tests and those against the clock. The aetiology varies: a progressive meningopathy or a subarachnoid haemorrhage: however over 30% of subjects present a mute anamnesis (idiopathic hydrocephalus). In this case too, the use of neuroimaging (and particularly of isotopic cisternography, which shows the reflux of tracer immersed in the lumbar subarachnoid space from the lateral ventricles), permits an early diagnosis. With the liquoral derivation, which is reserved to certain cases, a good level of success is obtained in the less ingrained forms that have minor ventricular enlargement.

Chronic trauma related dementias are forms of widespread cognitive deterioration following closed traumatic events of a severe nature. They are generally associated with the presence of an initial coma. Besides possible focal lesions, (intracerebral and epidural haematoma, subarachnoid or intraventricular haemorrhage, hypoxia), the most common damage mechanism is generally represented by a rotational type of movement, consequent to the acceleration-deceleration forces. A widespread axonal deterioration occurs, with multiple deep, often microscopic lesions brought about by the laceration of nerve fibres and by the functional disconnection between the cortical surface and subcortical white substance. This explains the prevalent subcortical characteristics of post-traumatic dementia.

Of particular interest is the picture of dementia decline resulting from repeated closed traumas generally with a sports related aetiology, such as in the so called pugilistic dementia or ‘punch-drunk syndrome’. Deterioration is accompanied by extrapyramidal signs and its symptomology can begin to appear even years after the sporting activity ceases. Infective dementias, instead, are those secondary forms due to bacterial action, virus or other pathogenic agents capable of causing damage to the Central Nervous System. The degree of irreversibility of the damage is strictly correlated to the speed of the diagnosis and the timeliness of the appropriate treatment. For example the AIDS-Dementia Complex, directly correlated to HIV infection of the SNC, represents a more frequently chronic progressive subacute disorder, characterised by a cognitive, motor, behavioural deterioration, decidedly distinct from opportunistic pathology or from other cerebral syndromes observable in other immuno-depressing and suppressing conditions.

Creutzfeldt-Jakob disease represents another classic form of infective dementia. Together with encephalopathy of the Fore population Kuru) and Gerstman-Straussler-Scheinker disease (of dominant autosomic transmission) it forms part of the so-called SNC infections from prions, infecting agents lacking in nucleic acid and resistant to chemical or physical agents. The form is a progressive dementia that is accompanied at an early stage by extrapyramidal symptoms, ataxia, myoclonias. The rapid progress of the dementia permits a differential diagnosis with AD and other degenerative dementias. Instrumental reports (including periodic EEG) and bioptic reports (spongious encephalic degeneration) are typical.

Finally mention should be made of the cognitive disorders that can appear in the course of psychiatric diseases, particularly mood depression. The expression pseudodementias has been coined for these cases. A pseudodemential syndrome would be present in around 15% of patients affected by Third Age depression. As a result there are diagnosis differential problems with AD (the nosographic entity of which differs from every manifestation of cognitive degeneration in the elderly), even more so if one considers that patients in the initial stages of AD often present, together with cognitive deficits, depressive type symptomology. The principal characteristics of pseudodementia are generally advanced age, a fairly quick first appearance (sometimes, concomitant with events of great emotional significance), a variable and fluctuating symptomology, awareness of one’s disorders, a family anamnesis often showing depressive precedents, and finally the absence of striking dementia episodes.

Cognitive disorders can appear in the course of psychosis. In this case it is likely that the degeneration can be attributed above all to a deterioration of the control functions (attention and motivation). Finally it should be stressed that the concept of secondariety of the form of dementia does not necessarily coincide with that of reversibility, even in cases of early diagnosis and immediate treatment. In fact it is estimated that cases of reversible dementia represent between 1% and 10% of the whole of the population affected by dementia. Therefore preventing senile dementia takes on an ever more critical role among medicine’s priorities, and the identification of protective factors is essential for the planning of appropriate programmes for interventions on the elderly.

Vincenzo Marigliano:  Faculty of Sciences of Ageing, La Sapienza University of Rome.