Neurodegenerative Disease Dementia Differential Diagnosis of Rapid Progressive Dementia

Uta Heinemann, Joanna Gawinecka, Christian Schmidt and Inga Zerr Dementia and Prion Research, Department of Neurology, University Medical School, Georg-August University Göttingen

Abstract

There is a broad range of diseases underlying dementia, of which Alzheimer’s disease is the most frequent in senile and pre-senile dementia. While senile dementia is predominantly caused by neurodegenerative or vascular disorders, in early-onset dementia other conditions are more relevant. Autoimmune, metabolic and genetic reasons should be evaluated, as well as toxic causes. A list of mutations associated with dementia is provided in this article. A higher proportion of potentially reversible conditions in pre-senile dementia highlights the value of detailed evaluation. Lumbar puncture is important in the diagnostic process to detect inflammatory changes, but dementia markers such as Aβ1–42 are also helpful in differential diagnosis. The value of cerebrospinal fluid markers for differential diagnosis is discussed in this article.

Keywords Dementia, differential diagnosis, pre-senile dementia, reversible dementia, cerebrospinal fluid markers

Disclosure: The authors have no conflicts of interest to declare. Received: 13 August 2010 Accepted: 15 October 2010 Citation: European Neurological Review, 2010;5(2):21–8 Correspondence: Inga Zerr, Department of Neurology, University Medical School, Georg-August University, Robert-Koch-Str 40, 37075 Göttingen, Germany. E: IngaZerr@med.uni-goettingen.de

The term ‘dementia’ is used to describe a decline in intelligence, memory and judgement as a result of brain disorders. The following cognitive deficits are common in dementia: impaired judgement (decline in intellectual performance and critical thinking), deficits in logical thinking and deductive reasoning, inability to understand or process information, memory deficits and loss of orientation to people, time and places. In some forms of dementia, such as frontotemporal dementia, personality changes are also present, and almost all forms are associated with a number of other deficits involving higher cortical functions, such as recognition of objects (agnosia), speech disorders (aphasia) and inability to perform learned purposeful movements (apraxia). This wide spectrum of neurological and psychiatric symptoms leads to markedly impaired cognitive and social function.

The most common cause of dementia is Alzheimer’s-type dementia (AD, which represents about 60% of all forms of dementia), followed by vascular dementia (VD, 15% of all dementia) and Lewy body dementia (LBD; also about 15%). Pre-senile dementias are characterised by much more heterogeneous clinical manifestations and a higher number of potentially reversible conditions (see Table 1).

In recent years there have been tremendous advances in our knowledge of the pathogenesis of neurodegenerative dementias, but for most dementias no tests are yet available that allow a definite diagnosis while the patient is still alive. There is also a lack of pre-clinical tests, in particular tests that could help predict the course of the disease. An early diagnosis is essential to maximise the efficacy of potential therapies, both because the likelihood of treatment success is better the earlier the diagnosis is made and because early

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differentiation between the different forms of dementia is important if we are to provide more sophisticated therapies in the future. Currently, the diagnosis of dementia is based on clinical criteria. Not only are imaging techniques important in excluding certain structural brain lesions or cerebral space-occupying lesions, but with the continuous improvement of magnetic resonance imaging and functional examination techniques, they are becoming more and more important for enabling clinicians to diagnose both neurodegenerative and reversible dementias. Cerebrospinal fluid (CSF) testing is another important diagnostic tool, details of which are discussed below. A combination of clinical presentation, neurological symptoms and technical findings can lead to a correct diagnosis (see Table 2).

Pre-senile dementia is defined as dementia with an onset of symptoms before 65 years of age. Since dementia is frequently caused by neurodegenerative diseases such as Alzheimer’s disease, it predominantly affects people around 70 years of age and has an increasing prevalence with older age. However, younger patients are also at risk. The prevalence of pre-senile dementia has been estimated at 67–81 per 100,000 in those between 45 and 65 years of age1,2

and pre-senile dementia accounts for about 10% of all dementia patients.3

As in older patients, of all the neurodegenerative disorders, Alzheimer’s disease is the most frequent underlying disease in pre-senile dementia, accounting for about one-third of cases, followed by vascular and frontotemporal dementia. By contrast, LBD is uncommon. Furthermore, some diseases appear typically in younger patients, such as variant Creutzfeldt-Jakob disease (CJD), which has a

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