Alzheimer’s disease (AD) is a neurodegenerative disease manifested by cognitive impairment and behavioural derangement (Hsu, Ku, Zanto & Gazzaley, 2015). It is the most common form of dementia. AD is a progressive disorder which has no cure but research has been done on methods in which to delay the onset of the disease. Deficits can be portrayed in cognitive domains such as attention, executive function and language (Celsis, 2000). Most cases of AD are sporadic with fewer cases being inherited (Israel, Yuan, Bardy, Reyna, Mu, Herrera, Hefferan, Van Gorp, Nazor, Boscolo, Carson, Laurnet, Marsala, Gage, Remes, Koo, Goldstein, 2012). Impairments seen in AD are seen in episodic memory as a result of medial temporal lobe damage and language and behavioural decline as a result of frontal lobe damage. This essay will explore studies which have given readers an insight into the disease pathology of AD, biomarkers for preclinical testing and current implemented treatments to delay the progression of AD. It is vital that AD is constantly researched in order to tackle the demands of an aging population since this does increase societal burden (Christensen, Doblhammer, Rau & Vaupel, 2009).
One important tool used to measure cognitive function is the Mini-Mental State Exam (Folstein, Folstein & McHugh, 1975). This is a 30-point test used to examine an individual’s orientation, memory, language, attention and visuo-spatial abilities. It is commonly used as one part of an assessment to test for dementia.
The build-up of amyloid beta (Aβ) which then destroys cells is outlined as the leading theory regarding AD diagnosis (Aisen, Cummings, Jack, Morris, Sperling, Frölich, Jones, Dowsett, Matthews, Raskins, Scheltens & Dubois, 2017). Aβ deposit outside neurons which destroy synapses which are vital connections to pass information through neurons. However, it has been questioned whether Aβ build-up alone contributes to AD progression. Hardy and Selkoe (2002) proposed that Aβ accumulation alone was not sufficient in the explanation of AD progression. Irizarry, McNamara, Fedorchak, Hsiao and Hyman (1997) found that transgenic mice undergoing Aβ deposition do not show neuronal loss. Further, Hardy and Selkoe (2002) stated that the number of Aβ deposits in the brain do not correlate with the cognitive impairment the patient experiences. There is another factor that should be considered in the process of neurodegeneration: tau pathology (Gomez-Isla, Hollister, West, Mui, Growdon, Petersen, Parisi & Hyman, 1997). Aisen et al., (2017) outline the accumulation of Aβ, formations of neurofibrillary tangles and neurodegeneration as our current understanding of AD pathology. Neurofibrillary tangles made of tau protein accumulate inside neurons which disrupts normal cell functioning thus killing them. As neurons and synapses die, brain tissue shrinks in key areas that support memory and language abilities.
Apolipoprotein E-e4 (APOE- ε4) is the major known genetic risk factor for AD. Lind, Ingvar, Persson, Sleegers, Van Broeckhoven, Adolfsson, Nilsson and Nyberg (2006) investigated the genetic risk factor, APOE- ε4, in relation to memory decline. They aimed to study synaptic dysfunction specifically on the parietal lobe. The study consisted of eighteen nondemented APOE- ε4 carriers which were then divided into two groups of: ‘decline’ and ‘nondecline’. This was based upon their longitudinal episodic memory performance in which the participants were measured at two intervals, 5 years apart – named T1 and T2. The study was strong in differentiating between the ‘decline’ and ‘nondecline’ groups due to no significant difference apparent between the groups in T1, but demonstrating a significant difference in T2. Therefore, the study was valid in stating the ‘decline’ group were indeed declining. The study found a significant difference between the ‘decline’ and ‘nondecline’ group in the left inferior parietal region shown as a result of the fMRI after T2. This comes as a result of the word categorization task. However, to further the results from this study, a facial recognition task could have been implemented in order to demonstrate a difference in the right hemisphere alongside the left hemisphere. Importantly, it should be noted that the hippocampus is the brain structure most involved with episodic memory. However, in this study there was no hippocampus atrophy meaning that this study was able to show the hippocampal behavioural effect without the fMRI showing this. This study by Lind et al., (2006) was crucial in outlining the significance of the parietal lobe for preclinical detection of AD and for demonstrating the link between the parietal lobe, atrophy and episodic memory performance. Further research looking into the rate of cognitive decline according to the APOE- ε4 allele is needed which can help to establish the effects of the APOE- ε4 allele and therefore focus work on treatments to slow down the progression of AD from an earlier screening mechanism.
Olofsson, Josefsson, Ekstrom, Wilson, Nyberg, Nordin, Adolfsson, Adolfsson and Nilsson (2016) looked at long-term memory decline and its link to olfactory deficits in carriers of the APOE- ε4 allele. This is very a crucial area to study since AD affects the vulnerable elderly society who can lose their appetite thereby losing weight. There is an overlap between brain areas relating to episodic memory and the olfactory nerve in the medial temporal lobes (Arshamian, Iannilli, Gerber, Wilander, Persson, Seo, Hummel & Larsson, 2013). Both episodic memory and olfactory deficits are considered to be early predictors of dementia (Olofsson et al., 2016) and therefore the study aimed to conduct a longitudinal study to explore the olfactory deficits alongside cognitive function over time. The methodology of the study was good since it was able to incorporate both immediate and delayed recall, since impairment may be seen in one and not the other. However, the study failed to account for both the left and right hemisphere of the brains – AD affects both hemispheres and therefore it is vital to test both parts. To do this, the study should have incorporated a non-verbal task to test the right hemisphere of the brain. In conclusion, the study was able to find a link between odor identification impairment and episodic memory decline but only in APOE- ε4 carriers.
Baudic, Dalla Barba, Thibaudet, Smagghe, Remy and Traykov (2006) aimed to study the cognitive effects of AD in the earliest stages which allowed them to examine the relationship between episodic memory and executive function. Baudic et al., (2006) were able to improve upon previous research, which identified the significant differences between very mild AD patients and controls on tasks such as Self-Ordering or Logical Matrices (Lafleche & Albert, 1995), by using more universally accepted tests for executive function. The study by Baudic et al. (2006) used a very strong methodology since it incorporated a range of tests. AD affects the left and right hemisphere and the frontal and temporal lobes so it was vital that all aspects were tested including verbal and non-verbal tasks. This paper was important to show support for the presence of executive dysfunction in the early stages of AD.
Sharma and Singh (2016) outline the use of cerebrospinal fluid (CSF) to confirm the presence of dementia as a result of the established biomarkers such as amyloid beta protein and tau protein. However, the process by which this fluid is obtained is a painful through lumbar punctures. This means it can be tricky for providing a diagnosis and also makes the results irreproducible. Sharma and Singh (2016) state that future research needs to identify inexpensive blood based methods in order to diagnose, identify and monitor the progression of AD.
Though there is currently no cure for Alzheimer’s disease, treatments are taken in order to decrease the progression of the disease thus delaying the problematic symptoms occurrence. Memantine is one drug used for those generally in the severe stage of AD. Antagonists of the N-methyl-D-aspartate (NMDA) pose issues for the functioning of the neuronal system (Chen & Lipton, 2006). This receptor is important for memory function. Glutamate receptors are vital to the normal functioning of the central nervous system (CNS). However, these receptors can be overly activated by excitatory amino acids which is thought to be detrimental to neurones which can lead to chronic neurodegenerative diseases such as AD. Aerosa Sastre, Sherriff and McShane (2005) studied the efficacy and safety of memantine for those with AD. In the moderate to severe AD group, the study found small beneficial effects at six months from taking memantine on cognition. In the mild to moderate AD group, detecting a change in cognition or behaviour was barely detectable. Olivares, Deshpande, Shi, Lahiri, Greig, Rogers and Huang (2012) found that during normal synaptic activity, NMDA receptors are open for just several milliseconds which doesn’t allow for memantine to act, however, during extended activation of the NDMA receptor, memantine can be an effective blocker. Further, memantine is a well-tolerated drug with patients reporting few and infrequent adverse effects. In conclusion, Olivares et al., (2012) found that though mematine was approved to treat severe AD, the results of its effectiveness are modest and therefore work into a new batch of drugs is underway to better clinical efficacy.
Aguirre, Woods, Spector and Orrell (2013) investigated the benefits of cognitive stimulation for dementia. Taulbee and Folsom (1966) looked at Reality Orientation (RO) in one of the first focused interventions to improve cognitive ability. RO intends to help those diagnosed with dementia focus on their immediate surroundings. It focuses on questions surrounding time, place and people. Aguirre et al., (2013) performed a meta-analysis aiming to evaluate the effectiveness of cognitive stimulation in dementia. The study did conclude with stating that cognitive stimulation does consistently improve cognitive function in those with dementia. However, improvements can be made to better this research. Firstly, Aguirre et al., (2013) stated in their methods that participants underwent a “first-assessment” which was not described. This does not make it clear to the reader of the purpose of this test and the outcomes of it. Further, the study included participants who had a diagnosis of dementia however the type of dementia was not differentiated. As a result, participants with AD were mixed with other dementia types which does not specialise towards specific groups making it difficult to see the effects of cognitive stimulation on one specific type of dementia. In addition to this, participants were able to receive the cognitive stimulation in a range of settings including their own home, residential setting or day care. These different settings would have some impact on the intervention session and therefore to improve upon this, a study must focus on participants receiving intervention in the same setting. This is better for validity of the results as well since there will be less external factors taking a part in the results. Further, the meta-analysis conducted included 15 studies of differing intervention times. This study can be improved in terms of this since differing intervention times will have differing results. To create a more controlled and structured study, the interventions received by the participants must all be of equal time. After the cognitive stimulation therapy had stopped, 10 months later the participants were tested on the MMSE but no significant changes to the result of this. It must be said that AD is a progressive disorder, so although the symptoms of the disorder may slow down, it is still progressive and does get worse over time so the MMSE score will not improve. In conclusion, the study found that cognitive stimulation does have a positive and beneficial effect on cognitive function in those with dementia. This is further supported by McDermott, Charlesworth, Hogervorst, Stoner, Moniz-Cook, Spector, Csipke and Orrell (2018) who reviewed 197 studies looking into the effective of psychosocial interventions for those with dementia. They found good evidence to support the idea of group-based cognitive stimulation to help improve social integration and social interaction for individuals with dementia. Further research is needed to investigate the longer-term outcomes of stimulation specifically tailored to AD.
Lane, Ayton and Bush (2018) explored the connections of AD with iron. Iron has many important roles in the CNS involving mitochondrial energy transduction and function, catabolism and myelination. Changes in brain iron homeostasis can increase levels of this metal which can cause oxidative stress and damage to cellular organisms. AD has been linked to iron dyshomeostasis in which the authors concluded that alongside cell death, neuronal loss involves ferroptosis which is a newly identified type of cell death dependent on iron concentration, characterised by build-up of lipid peroxides. Guo, Liu, Fan, Yang and Wang (2018) added to research by Lane et al., (2018) by stating that oxidative stress may promote aggregation of tau protein. Future research must outline the role of iron in the development of AD to explain the occurrences of this.
To conclude, there is constant new research being conducted in regards to AD. As a result of the aging population that is now present, interventions and research towards slowing down this progressive disorder must be prominent. Further, it is vital to identify the biomarkers of AD and outline tests can be conducted to predict those who are more likely to develop AD. As a result of this, research must be targeted towards slowing down this disease earlier in its course as this will have a more positive impact on the individual’s quality of life from an earlier stage and they will receive the maximum benefits of any treatment provided.
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