Alzheimer's Disease
Pick's Disease
Frontal Lobe Degeneration
Frontotemporal Dementia
Lewy Body Dementia
Primary Progressive Aphasia
Cortico-Basal Degeneration
Progressive Supranuclear Palsy (Steele Richardson Olszewski Syndrome)
Prion Diseases

ALZHEIMER’S DISEASE

AD may be sporadic or familial and the age of onset may vary enormously from around forty to over ninety, although it is predominantly a disease of old age. In familial cases, the age at onset within a family may be fairly constant.

Several abnormalities in the genetic make up (gene mutations) have been identified in individuals with familial AD; the cause agent of the sporadic form of the illness is probably multifactorial.

The gene responsible for making the amyloid protein is on chromosome 21 and a mutation in this gene has been shown to cause AD in three families in Britain and about fifteen families world-wide. Many of the families that have a very young age of disease onset have been shown to have a mutation in a gene on chromosome 14 now called Presenilin 1. So far at least 25 different mutations have been described. Mutations in a similar gene, Presenilin 2, on Chromosome 1 have also been described; the age at onset in these families is later. In these families the inheritance is autosomal dominant.

Late onset AD has been linked with chromosome 19 and type of Apolipoprotein. Although there is an increased predisposition to AD with the genotype Apolipoprotein 4 it is not conclusive and it is possible to have AD but not Type 4 and likewise to have Type 4 but not develop AD.

Neuropathologically, the different forms of AD cannot yet be differentiated.

PICK’S DISEASE

In 1892, Arnold Pick, a German neurologist, described a man who had presented in life with progressive loss of language. After death the patient’s brain was shown to have asymmetric atrophy as opposed to Alzheimer’s disease where the atrophy is more general. In Pick’s disease the frontal and temporal lobes are most affected. In addition, brain cells in these areas are sometimes found to be abnormal and swollen. These abnormal cells (Pick cells) together with the presence of abnormal staining within cells (Pick bodies) are the hallmark of the disease.

When these typical features are not seen on post mortem examination but the same areas of the brain are affected by cell death, the case may be described as Pick’s syndrome or frontotemporal Dementia.

Pick’s disease varies in the way it affects individuals. There are however, a common core of symptoms. Some or all of these may be present at different stages of the disease.

The more common symptoms include:

• personality change: loss of inhibitions/rudeness/impatience/inappropriate behaviour 
• failure to recognise objects 
• using objects wrongly 
• development of routines 
• speech problems, echolalia (repeating what is said to the patient) 
• overeating, changes in dietary preference, obsessional cravings for certain types of food 
• attention problems 
• changes in sexual behaviour

FRONTAL LOBE DEGENERATION

A frontal dementia but without the typical changes seen on neuropathological examination in Pick’s disease although cell loss in the frontal lobes is apparent. The onset is usually slow with only changes in personality seen for some time. This is followed by changes in mood and behavioural disturbance. It may be sporadic or familial, and an as yet unidentified mutation on a gene on Chromosome 17 is believed to be the cause of some cases.

FRONTOTEMPORAL DEMENTIA

This is a clinical term to describe patients with personality (frontal lobe) or language (temporal lobe) changes. It includes the specific diseases of Pick’s disease and frontal lobe degeneration amongst others.

LEWY BODY DEMENTIA

Lewy Body dementia has been increasingly recognised over the past 5-10 years. Lewy bodies are areas of abnormal staining (distinct from Pick bodies and neurofibrillary tangles) found within brain cells. They are found in a particular area of the brain stem, the substantia nigra, in Parkinson’s disease. In Lewy body dementia they are found in the cerebral cortex, either alone or in combination with the senile plaques of Alzheimer’s disease. Lewy body dementia may present as:

late onset Parkinson’s disease followed months or years later by visual hallucinations, episodes of confusion, memory loss and then global dementia
or
cognitive or psychiatric symptoms followed by milder Parkinsonian features later in the course of the disease.

• fluctuating cognitive performance with episodes of confusion 
• hallucinations and/or paranoid delusions 
• early gait disturbance 
• any combination of rigidity, bradykinesia, tremor and flexed posture 
• temporoparietal dementia with inattention in a patient with Parkinson’s disease

Anybody can develop Lewy Body disease. Studies which have looked at the brains of people with dementia after they have died suggest that it is relatively common although prevalence figures do vary. It appears to affect men and women alike.

As yet it is impossible to identify risk factors for developing the disease. However, rare ‘familial’ cases of Lewy Body disease have been described. Although there is no cure for Lewy Body disease it is sometimes possible to treat some of the symptoms of this disease. The depression which accompanies this disease for example will usually respond to antidepressant therapy.

PRIMARY PROGRESSIVE APHASIA

Gradual dissolution of speech is the salient finding for at least two, and up to fourteen years. Patients are usually aware of their speech/language deficit. This disease may be of senile or pre-senile onset. There is loss of cells in the speech areas of the frontal lobe. The disease is difficult to distinguish from Pick’s disease during life.

CORTICO-BASAL DEGENERATION

Symptoms include apraxia, rigidity, involuntary movements, dystonia, the ‘alien limb’ sign, dysarthria and a supranuclear disorder of the eye movement. Mental impairment occurs late in the course of the disease but some patients lose language early. Post mortem changes include fronto-parietal atrophy and subcortical loss. There are swollen cells similar to Pick cells but no Pick bodies.

This disease usually affects people in their 60’s to 80’s. Males and females are equally affected.

PROGRESSIVE SUPRANUCLEAR PALSY (Steele Richardson Olszewski Syndrome)

A disease affecting the brain stem. It varies from patient to patient but may affect balance, vision, swallowing and speech. Personality change also occurs including forgetfulness, lack of interest and loss of enthusiasm, irritability, depression and impaired concentration, ie the features of a frontal dementia.

PRION DISEASES

These are a closely related group of neurodegenerative diseases known to present in humans [Kuru,Creutzfeldt Jakob Disease and Gerstmann Straussler-Scheinker Syndrome] and animals [e.g. Scrapie, Transmissible Mink Encephalopathy and Bovine Spongiform Encephalopathy]. They are all caused by an alteration of the prion protein in the brain, which is present in all of us, from its normal to an abnormal form. It is transmissible by exposure to the abnormal (scrapie form) of the prion protein. It can also be inheritable (familial) due to mutations in the prion protein gene.

Kuru: believed to be transmitted via ritualistic cannibalism. Now virtually extinct, the disease presented with trembling, then deterioration in speech and motor incapacity.

Classical Creutzfeldt Jakob Disease (CJD): is a sporadic form of the disease. It occurs in middle age and elderly and is a very rapidly progressive dementia (death within 6 weeks to 6 months) with myoclonus.

Gerstmann Straussler Scheinker Syndrome and familial CJD: arefamilial diseases due to mutations in the prion protein gene. The course of the disease is longer than sporadic.

Iatrogenic CJD: These are cases caused by exposure to the abnormal prion protein either from neurosurgery, cataract transplants or injections of contaminated pituitary extracts of growth hormone.

All of these cases show a spongiform degeneration at post mortem together with deposition of the abnormal prion protein.

New Variant CJD: This was described last year (now 21 cases). It occurs in young people with prominent early behavioural change. The neuropathology is similar to Kuru and at a molecular level there are similarities to BSE suggesting that they may be linked.