Compare the effectiveness of neuroimaging approaches to predict the future onset, and to differentiate between the different clinical stages, of Alzheimer’s disease Alzheimer’s disease is characterised as a dementia with the presence of amyloid plaques and neurofibrillary tangles which leads to neuronal cell death (Hardy & Higgins, 1992).
The most major symptom shown in Alzheimer’s disease is the degeneration of cognitive function (memory, reasoning, attention, language etc. and it is crucial to diagnose Alzheimer’s disease in the early clinical stages where the pathological damage isn’t too serious so to prevent further damage occurring at a rapid rate (Amieva, et al. , 2008). Clinical diagnosis and research of Alzheimer’s disease use Braak staging to classify the pathology and damage to certain regions of the brain of Alzheimer’s disease. In Braak stages I & II, neurofibrillary tangles are confined to the entorhinal region, but show very little clinical significance.
Braak stage III & IV show neurofibrillary tangles in the cerebral cortex, however there is not extensive damage. There are also changes found in the hippocampus and stages III & IV show cognitive impairment and slight changes in personality. Stages V & VI show serious damage in the neocortex with large numbers of neurofibrillary tangles in the cerebral cortex. Clinically, these last 2 stages represent conventional Alzheimer’s disease which is shown as severe cognitive impairment and personality changes (Braak & Braak, 1995).
As well as brain histology to diagnose and research Alzheimer’s disease, different types of neuroimaging can be used to help to diagnose the clinical stage of Alzheimer’s disease and therefore the future onset of Alzheimer’s if an individual is only presenting the early clinical stages. These different neuroimaging techniques have advantages and limitations which will be discussed.
There are two main types of neuroimaging techniques, structural imaging including magnetic resonance imaging (MRI) and computerised tomography (CT) and functional imaging including positron emission tomography (PET) and single photon emission computerised tomography (SPECT) (Mueller, et al. , 2005) Both MRI and CT produce very similar information via the detection of neuronal loss related to Alzheimer’s using structural imaging (Mueller, et al. , 2005).
The best MRI marker is assessing hippocampal atrophy with high resolution T1-weighted MRI, but assessment of coronal T1-weighted MRI is the easiest technique to measure medial temporal lobe atrophy. However, assessment of the medial temporal lobes is insufficient evidence to clinically diagnose Alzheimer’s disease at the stage of mild cognitive impairment (MCI) whilst also not showing enough specificity to confidently distinguish between Alzheimer’s and other dementias (Frisoni, et al. 2010).
On the other hand, assessment of the medial temporal lobe atrophy with higher specificity is a very strong predictor to distinguish those who will develop Alzheimer’s and those who will not (Johnson, et al. , 2012). Overall, structural MRI scanning is good a predicting the future onset of Alzheimer’s disease and is also widely available however, has trouble distinguishing Alzheimer’s from other dementias due to the low molecular specificity of structural MRI (Johnson, et al. , 2012).
Computerised tomography (CT) imaging is used to identify structural changes in the brain, especially focal atrophy. However, CT imaging shows low reliability as CT imaging is not used to diagnose Alzheimer’s, it is used to only exclude other dementias, but can lead to the only possibility being Alzheimer’s. CT imaging cannot predict the future onset of Alzheimer’s, can only identify brain abnormalities and it is known that MRI has a higher resolution so can produce more precise images of the brain’s anatomy (McGeer, et al. 1986) (Smith & Jobst, 1996).
Advantages of CT imaging are that is has a shorter acquisition time than MRI so less chance of artefacts being imaged whilst, also not being as restricting and claustrophobic as MRI (Mueller, et al. , 2005). There are two major types of PET imaging, 18F-fluorodeoxyglucose positron emission tomography and amyloid PET. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is used most regularly for functional imaging of Alzheimer’s disease.
It measures the cerebral glucose metabolism in the brain in the presence of a glucose analogue and the radiotracer fluorine-18 to measure brain perfusion (Lee, et al. , 2003) (Johnson, et al. , 2012). FDG-PET is very good at detecting the early stages of Alzheimer’s disease as glucose hypometabolism is shown, mostly in the limbic cortex, and frontal cortex as the disease progresses, therefore links to a change in neuronal function (which is tau-mediated). This then means that the different clinical stages of Alzheimer’s can be identified (Mueller, et al. 2005).
In addition, FDG-PET is also very good at distinguishing between different dementias when first evaluations are uncertain, however there is no FDG-PET criteria for dementia at the stage of MCI and should not be the only imaging measure being used to diagnose Alzheimer’s (Mosconi, et al. , 2008). Other limitations surrounding FDG-PET is that it is very expensive and is not widely available. It is also invasive due to the use of intravenously administered radiotracers (Johnson, et al. , 2012).
Another type of PET imaging is amyloid PET. Amyloid PET is normally only used in vivo for A? pathology and not normally used for clinical diagnosis. The biggest strength of amyloid PET imaging is that is has enabled the clinical use of measuring A? content in the brain. However, the main limitations of amyloid PET is the cost and availability of the imaging so therefore, is not commonly used in clinic. In addition, amyloid PET is not a good marker for measuring the development of Alzheimer’s disease (Johnson, et al. 2012).
Single photon emission computerised tomography (SPECT) imaging is another form of functional imaging and are more widely available that PET scanners with also a wider range of isotopes that can be used. It is used in the early diagnosis of Alzheimer’s whilst also differentiating between different forms of dementia (Lee, et al. , 2003). SPECT imaging works by using a radiotracer and emitting a single gamma ray in order to measure regional cerebral blood flow (Bhriain & Lawlor, 2002).
With regards to the early diagnosis of Alzheimer’s, SPECT imaging can also be a useful predictor in the future onset of Alzheimer’s by showing that those with temporo-parietal defects are more likely to develop Alzheimer’s. Therefore, the presence of temporo-parietal hypoperfusion is found in those with Alzheimer’s when imaged with SPECT (Bhriain & Lawlor, 2002). SPECT imaging does show limitations such as the lack of availability. SPECT is extremely specialised and is only really used in research centres rather than in the clinic due to the specialisation. Therefore, most diagnoses of Alzheimer’s are done without the use of SPECT.
In conclusion, although all neuroimaging techniques are effective in certain ways, they should not be used in isolation in the diagnosis of Alzheimer’s disease and should be used together instead for example MRI and FDG-PET. It has been shown that with structural imaging (CT and MRI) especially in CT imaging shows very low molecular specificity and resolution so it can be challenging to recognise certain brain abnormalities with precision. This therefore means that Alzheimer’s disease cannot be diagnosed at certainty from just CT imaging (Smith & Jobst, 1996), other forms of imaging will be required as further evidence.
Also structural imaging has difficulties identifying the clinical stages of Alzheimer’s due to the low resolution and molecular specificity. Another form of imaging which could be used in conjunction with CT or MRI imaging is functional imaging in the form of FDG-PET and/or SPECT. FDG-PET is very good at distinguishing between different forms of dementia whilst also providing a good predictor to the future development of Alzheimer’s in the early clinical stages (Mosconi, et al. 2008) (Mueller, et al. , 2005) and can be used as further evidence of Alzheimer’s disease when it is seen as unsure when first imaged via CT or MRI.
Overall, all these techniques are useful in the prediction of future development of Alzheimer’s and the differentiation between different clinical stages and dementias, however all show certain limitations, whether that be low resolution or lack of availability, so should be used together to achieve the maximum effect and best diagnosis.
