Young onset dementia.(Review)

Postgrad Med J 2004;80:125-139. doi: 10.1136/pgmj.2003.011171

Young onset dementia is a challenging clinical problem with potentially devastating medical and social consequences. The differential diagnosis is wide, and includes a number of rare sporadic and hereditary diseases. However, accurate diagnosis is often possible, and all patients should be thoroughly investigated to identify treatable processes. This review presents an approach to the diagnosis, investigation, and management of patients with young onset dementia, with particular reference to common and treatable causes.

**********

Dementia in younger people (young onset dementia, YOD) is increasingly recognised as an important clinical and social problem, with frequently devastating consequences for both the sufferer and those who care for them. (1) Prevalence rates of YOD have been estimated between 67 to 81 per 100 000 in the 45 to 65 year old age group (2 3); thus there are currently approximately 10 000 patients with YOD in the United Kingdom alone. YOD poses a diagnostic challenge and may present with a wide variety of subtle behavioural, cognitive, psychiatric, or neurological symptoms. While the degenerative dementias characteristically affect older patients, they are also an important cause of YOD: indeed, Alzheimer's disease is the commonest single cause of YOD with an estimated 3000 cases in the United Kingdom, followed by vascular dementia and the fronto-temporal lobar degenerations (table 1). The young onset forms of these diseases are frequently familial. (4) Some degenerative dementias such as variant Creutzfeldt-Jakob disease typically occur in the young patient. In contrast, Lewy body dementia, which accounts for 20% of cases in patients over 65 years of age, accounts for only a small proportion of YOD.

The differential diagnosis of YOD is wide (tables 2 and 3). Dementia is very rare before the age of 40: in young adults and adolescents, genetic and metabolic disorders predominate and many present as a "dementia-plus" syndrome, where cognitive impairment occurs in the setting of more widespread neurological disturbance. The additional features of pyramidal, extrapyramidal, cerebcllar, or peripheral nerve involvement are key diagnostic clues in this group (table 3) and help to direct investigations. Most inherited disorders of metabolism are autosomal recessive: in these diseases, the absence or partial inactivity of the affected enzyme leads to accumulation of abnormal material in lysosomes or peroxisomes. (5) Mitochondrial diseases have variable inheritance, as components of the respiratory chain are encoded both by nuclear DNA and maternally inherited mitochondrial DNA. (6) Many of the dementia-plus syndromes and metabolic disorders have "subcortical" cognitive impairment that may be misinterpreted as a pseudodementia. Changes in personality and mood, apathy and cognitive slowing are common, whereas memory may be relatively spared. In addition, drugs and toxic exposures should always be considered in younger adults: in approximately 10% of cases, YOD is a consequence of chronic alcohol abuse. (2)

This review will focus on common and treatable causes of YOD and outline general principles of investigation and management.

PRIMARY NEURODEGENERATIONS