The early diagnosis of Alzheimer’s disease is important in order for those developing the disease to benefit from current treatments available – most of which have the greatest effect in the initial stages of the condition.

Expert opinion should be sought without delay the moment there is any concern of Alzheimer’s disease as treatments can be prescribed which have the potential to keep the more severe symptoms at bay. Indeed, new drugs are being developed which are delivering extended periods of remission although, as is the case with most neurodegenerative conditions, there is considerable variability between individuals regarding periods of remission. To date, there is no cure for the disease and no viable strategy for the neuroprotection of vulnerable populations of cells, thus preventing the onset of the disease.

Diagnosing Alzheimer’s disease will often involve a range of different tests and information gathering, therefore, the results of investigations undertaken may take several weeks to collate. The general practitioner (GP) will invariably refer a patient to the neurological or psychiatric services for diagnoses although most GPs will have access to a specialist ‘memory clinic’ provided by one of these services. While specific tests may be conducted which directly involve the patient, family members may also be approached with the patient’s consent, if an inherited form of the disease is suspected or if the patient himself feels unable to provide an accurate report of the symptoms experienced or time of onset.

The diagnosis process initially seeks to eliminate other possible causes of the symptoms reported. For example, having recently received general anaesthesia or suffered from concussion, a brain tumour or depression may be suspected. If, after examination other conditions are excluded and a dementia is suspected, the type of dementia suffered will be explored. While it is difficult to distinguish all dementias, it is possible to differentiate Alzheimer’s dementia from the next most common form - Vascular dementia as their characteristics differ in key respects.

Key differences between Alzheimer’s and Vascular dementias:

FEATURE ALZHEIMER’S DISEASE VASCULAR DEMENTIA
AGE OF ONSET
Usually after 65 years
Usually after 40 years
SEX
More common in women
More common in men
COURSE
Slowly progressive
Stepped
IMPAIRED INSIGHT, INTELLIGENCE & PERSONALITY
Early onset
Late onset
PHYSICAL SIGNS & SYMPTOMS
Usually few. Appear late in the illness
Usually occurs and of sudden onset

Genetic Testing:

dnaA blood sample will enable the individual’s DNA to be subjected to a range of genetic tests which will establish whether or not any of the known genetic mutations have been inherited. Such DNA analyses will also allow profiling of the ApoE4 variant and whether the E4 allele is present either as a single copy or two copies.

Genetic screening will be undertaken in tandem with a detailed family history being compiled by the physician, psychologist or nurse. If an inherited form of Alzheimer’s disease is suspected, there should be a diagnosis of the disease in one of the patient’s parents and 50% of the siblings in each generation. In such cases it is important to obtain as much information about grandparents, parents, aunts, uncles and cousins in addition to brothers and sisters.

Most cases of Alzheimer’s disease, however, occur spontaneously and diagnosis follows the completion of a number of ‘recall’ and ‘recognition’ tests which are able to confirm a diagnosis of the disease in approximately 85% of instances. This level of accuracy is based on evidence that word learning and recall performance are impaired in early stages of the disease. These tests are not only used as a marker of memory loss for diagnostic purposes, but also when used at regular intervals, they can indicate the decline in an individual’s performance as the disease progresses.

Psychological Testing:

pen and paper drawing tests
A person suffering from Alzheimer’s
disease finds it difficult to copy the
drawing on the left and attempts
resemble the image on the right.

There are a number of published psychological tests used for the diagnosis and monitoring of the decline of Alzheimer’s disease. These rely on the examination and assessment of memory and other cognitive functions, and provide important feedback when testing the efficacy of drugs or other treatments. Examples of these tests are: Alzheimer’s Disease Assessment Scale (ADAS); Clinician Interview Based Impression of Change (CIBIC); Clinician Dementia Rating scale (CDR); Cambridge Dementia Examination (CAMDEX); and the Mini-Mental State Examination (MMSE). The information used in these tests is collected from other assessments, some of which include the following:

  • Word list recall tests – which involve the individual recalling items from a list of objects read out loud. Recall may be sought immediately or after a short interval.
  • Naming of objects presented pictorially.
  • Recognition of celebrities from pictures presented.
  • Questions on current affairs and personal events.
  • Pen and paper drawing tests (see right).

Brain Scans:

alzheimers brain scan

Images of the brain may be obtained through several different systems which provide different information about the brain’s integrity and status. Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) may each aid the monitoring of the neurodegenerative process through loss of brain volume, increases in the size of the ventricles, and the brain’s activity.

brain tissueThe Alzheimer’s brain tissue (left) reflects the loss of cellular structure, increased cavities and reduced activity when compared to a normal tissue (right).

During the early stages of Alzheimer’s disease, the loss of cellular integrity may not be sufficient to be detected by such imaging techniques. Therefore, they are not routinely included in early diagnostic testing although, they are of value in excluding other neurological problems such as brain tumours or mini-strokes.

Biopsies:

Examination of brain tissue for the presence of plaques and tangles (the key features of Alzheimer’s disease) can rarely be justified due to the risk of causing additional cognitive impairment to the individual.

Lumbar Puncture:

Analysing cerebrospinal fluid (CSF) located in brain’s cavities provides information regarding the status of the brain’s neurochemical breakdown products. The breakdown products of tau protein, one of the two major proteins intrinsic to the disease, are known to be present at a higher level in the CSF of Alzheimer’s disease patients than their age matched counterparts. However, to obtain a sample for analyses requires a lumbar puncture which can be both invasive and unpleasant.

Urine Analyses:

Breakdown products of tau and beta-amyloid are reported to correlate with the presence of a compound known as isoprostane eliminated from the body via urine. Studies have demonstrated that the level of isoprostane is elevated in the urine of Alzheimer’s disease sufferers. However, whether or not it is sufficiently sensitive to provide a reliable diagnostic test remains to be seen.

Eye Testing:

Eye drops which highlight diseased cells, show that the amount of damage to cells in the retina directly corresponds with brain cell death and that there is a pattern of retinal cell death characteristic of Alzheimer's Disease. This research indicates that cells start to die 10 to 20 years before the symptoms of the disease become evident. If verified, this test would permit people to be screened in middle age for signs of the disease and treatments to be prescribed before cognitive function became impaired.

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