Evidence for Preclinical Alzheimers Disease - Essay Example

A Critical Review of “β-amyloid (Aβ) Imaging and Memory in Non-Demented Individuals: Evidence for Preclinical Alzheimer’s Disease.” Introduction In conducting a search for research studies in diagnosing dementia and Alzheimer’s disease, it became clear that the majority of research concerns literature reviews of older studies concerning such diagnostic determinations. Additionally, much of the research available for reviews, concerns studies made on specific issues regarding elderly people who have already been diagnosed with dementia and potential Alzheimer’s disease. This paper looks at a study of non-diagnosed elderly patients who show clinical potential for developing dementia or Alzheimer’s disease (AD) and provides a foundation for the burning question below. A personal research review model (Appendix A: rubric) was created to provide a linear process discussion of the relevant questions. The burning PICOT question for this paper and subsequent research is: “In elderly people (P=70+), how are cognitive skills measured in dementia and potential Alzheimer’s disease (I=Issue), as compared to younger adults (C), affect the lifestyle of those diagnosed (O), and how long before a diagnosed patient is no longer legally or medically functional (T)?” (Melnyk & Fineout-Overholt 2011). Funding for this research was provided by Neurosciences Victoria, Austin Hospital Medical Research Foundation, and the Commonwealth Government of Australia Department of Health and Ageing, with unrestricted educational research grants. Funding was also provided by the Commonwealth Government of Australia to publish under Open Access (Pike et al., 2007). The Research Study The main reason for conducting this research study (Pike et al., 2007) was to find common bio-indicators in a currently healthy aging senior which provides a predication for eventually moving into dementia and/or Alzheimer’s disease (AD). The β-amyloid (Aβ) presentation is commonly found in those diagnosed with AD, yet it can also occur in normal healthy aging adults as well without affecting the person in any manner. The 11C-PIB-PET brain scan was used in the study to provide a qualitative marking process with three groups: the healthy ageing (HA) adults, the mild cognitive impaired (MCI) adults, and those diagnosed with AD (Pike et al., 2007). Many of the previous research studies have only used formally diagnosed patients with dementia or AD. PIB stands for Pittsburgh Compound B, which is a benzothiazole derivative that will bind to Aβ and is seen during the positron emission tomography (PET) imaging process, also known as the 11C-PIB-PET brain scan (Pike et al., 2007; Kadir et al., 2011). While ageing adults may present some cognitive difficulties up to nine years before being officially diagnosed with dementia or AD, it is suspected that the precursors of both diseases are already evident before clinical diagnosis occurs (Jeffries & Agrawal, 2009; Lloyd, 2014). Ageing adults over 75 years of age, have shown fairly moderate amounts of Aβ plaques in the cerebral cortex in 25%, which is also equivalent to the prevalence of dementia in those 85 years or older. This presents that changes actually occur long before diagnosis of AD, for example (Pike et al., 2007). The Methodology While over 200 participants were first reviewed for inclusion, only 96 participated in the study, once exclusions were applied. Most exclusions were made at the beginning and the last exclusion applied after the MMSE if the results were less than 12. The final inclusion was that AD participants met the criteria presented by NINCDS-ADRDA; all MCI participants met published consensus criteria that they were not normal but not demented, had subjective report of decline and objective report of impairment, and no significant functional loss ({Pike et al., 2007). The HA participants were recruited from the longitudinal healthy ageing study underway at the Mental Health Research Institute of Victoria. The final step for all participants was a genomic DNA test by PCR amplification for the determination of apolipoprotein-E (ApoE). Groups were well-matched in ages, educational levels and gender. The HA group had less of the ApoE ε4 allele (Fisher’s exact test = 0.004), but have a more first degree relative with AD (Fisher’s exact test = 0.009), as compared with the other two groups (Pike et al., 2007). The groups were given a battery of tests along with the MMSE which included the 30-item Boston Naming Test (BNT), backwards test (DSp(b)), and Digit Symbol-Coding test from WAIS-III. Other tests were the Verbal Learning Test-2nd edition (CVLT-II), Rey Complex Figure Test (RCFT), letter fluency and category fluency tasks (Pike et al., 2007). Selected Participant Characteristics and Composite Scores (Fig. 1, Pike et al., 2007, p. 2839) A composite episodic memory score was calculated using the average of the z scores, with HA as the reference, for RCFT and CVLT-II, both long delay. Then a composite non-memory cognition score provided the average performance on non-episodic memory by taking the average of the z scores for BNT, letter fluency, category fluency, DSp(f), DSp(b), DS-C and RCFT copy (Pike et al., 2007, p. 2838). A 3-D spoiled gradient echo (SPGR) TI-weighted MRI was conducted on all participants for preliminary screening and for registering with PET images. Over 11 ± 22 days, participants also received the 11C-PIB-PET scan, and after 40 to 70 minutes of the PIB injection, PRT standardized uptake value (SUV) data acquired was summed and normalized to the cerebellar cortex SUV, in order to obtain the SUV ratio (SUVR), to act as the control point (Pike et al., 2007). A few more calculations were made before statistical analysis was conducted on findings. Typical Mid-Sagittal and Transverse 11C-PIB-PET Images (Fig. 2, Pike et al., 2007, p. 2840) Statistical Analysis IBM’s SPSS (v.11) was used to determine differences between groups, using X2 tests. The means of AD, HA to MCI were done through independent sample t-tests, including within MCI subgroups. Pearson’s correlations were also used for assessing bivariate relationships and multiple regression analyses were performed on possible mediating effects of relational diagnosis between PIB binding and cognition. A moderated regression was additionally conducted to discover any relational differences in PIB binding and memory across groups as well. Along with a few other processes, gender, age and education, as variables, were controlled in all analyses. The study goes on to provide a very robust process of further in-depth analyses of the data retrieved, providing a solid foundation for episodic memory and PIB binding (Pike et al., 2007). Results The results showed that significantly lower neocortical PIB binding was found in the HA group than was seen in the MCI group, which, itself, was lower than the AD group at P < 0.001. Of the AD cases, 97% were PIB-positive, while MCI was 61% and HA was 22%. The six participants of the MCI group, who were non-amnestic, had a negative PIB scan, while 18 participants of the amnestic subgroup and 2 of the subjective subgroup were PIB-positive. Of the MCI participants with a PIB-positive scan, 80% carried the ApoE ε4 allele, as compared to the 23% with a PIB-negative scan (Pike et al., 2007). HA participants had the higher composite scores for both memory and non-memory cognition than did the MCI participants. The MCI participants had significantly higher composite scores than did the AD group, but the amnestic MCI subgroup had worse memory scores than did the non-amnestic MCI group. Under a series of multiple linear regression analyses, PIB binding was related to AD diagnosis, but not with HA. Conclusion Many different methods of analyses were performed for different outcomes in correlations and multiple regressions. This study provides a good foundation for further research in correlations, particularly through using the 11C-PIB-PET brain scan in correlation with the multiple cognition tests provided (Galvin & Sadowsky, 2012), and that Aβ deposition is connected to impaired episodic memory in non-demented patients, providing the preliminary marker needed for further research studies in how to track potential cases of dementia and Alzheimer’s disease. More precise methods still need to be found but the imaging scan process, along with cognitive testing provides a big step forward. Appendix A: Rubric “β-amyloid (Aβ) Imaging and Memory in Non-Demented Individuals: Evidence for Preclinical Alzheimer’s Disease.” Brain, 130, 2837-2844. (Pike et al., 2007). 1 Purpose of the study The purpose of the study is to find common biomarkers of one type or another in a healthy aging senior adult which indicate that someone will eventually move into dementia and/or Alzheimer disease. 2 Type of study (RCT?) This is a comparison study between healthy aging (HA) adults, mild cognitive impairment (MCI) adults, and Alzheimer’s Disease diagnosed (AD) adults. 3 Who were the researchers? All of the researchers were professionals in the medical field, including practioners, professors and clinicians in Australia. 4 Were they funded and was their bias? There were no restrictions with the funding and as far as could be seen, no bias. 5 Who were the subjects? Inclusions. There were three groups of aging adults: HA (32), MCI (33), and AD (31), for a total of 96 respondents. Those who could not speak English were excluded, as well as those who tested MMSE less than a 12 score, or had a brain injury or history of alcoholism. 6 How were they gathered? HA participants were recruited from the ageing study underway at the Mental Health Research Institute. 7 What was the intervention? After preliminary exclusions, the MMSE was administered, along with the 30-item Boston Naming Test (BNT), backwards test (DSp(b)), and Digit Symbol-Coding test from WAIS-III. Other tests were the Verbal Learning Test-2nd edition (CVLT-II, Rey Complex Figure Test (RCFT), letter fluency and category fluency tasks. 8 What was the study duration? Between 11 to 22 days. 9 Were there any limitations? No. 10 What were the results? Lower neocortical PIB binding found in HA (22%) group. MCI group was higher (61%) than HA, but much less than the AD group (97%). Of the MCI participants with a PIB-positive scan, 80% carried the ApoE ε4 allele, as compared to the 23% with a PIB-negative scan 11 What type of analysis was used? A composite episodic memory score was calculated using the average of the z scores, with HA as the reference, for RCFT and CVLT-II, both long delay. Then a composite non-memory cognition score provided the average performance on non-episodic memory by taking the average of the z scores for BNT, letter fluency, category fluency, DSp(f), DSp(b), DS-C and RCFT copy. Multiple regression tests were done, along with t-tests and correlation tests. 12 Were proper ethics and permissions observed? Written informed consent was obtained prior to participation. Ethics approval was given by the relevant committees at Austin Health and Monash University. 13 What was not discussed? The study did not say where the AD and MCI patients came from. Resources Galvin, J.E., & Sadowsky, C.H. (2012). Practical Guidelines for the Recognition and Diagnosis of Dementia. Journal of the American Board of Family Medicine, 25, 367-382. Retrieved from http://www.jabfm.org/content/25/3/367.full.pdf+html. (Galvin & Sadowsky, 2012) Jeffries, K., & Agrawal, N. (2009). Early-onset Dementia. Advances in Psychiatric Treatment, 15, 380-388. Retrieved from http://apt.rcpsych.org/content/15/5/380.full.pdf+html. (Jeffries & Agrawal, 2009) Kadir, A., Marutle, A., Gonzalez, D., Scholl, M., Almkvist, O., Mousavi, M., ……. Nordberg, A. (2011). Positron Emission Tomography Imaging and Clinical Progression in Relation to Molecular Pathology in the First Pittsburgh Compound β Positron Emission Tomography Patient with Alzheimer’s Disease. Brain, 134, 301-317. http://brain.oxfordjournals.org/content/134/1/301.full.pdf+html. Lloyd, B.K. (2014). Identifying Early Indicators of Subjective Memory Concerns in Seniors. (Thesis). Retrieved from https://www.ruor.uottawa.ca/en/bitstream/handle/10393/30920/Lloyd_Brittany_2014_thesis.pdf?sequence=1. (Lloyd, 2014) Melnyk, B.M., & Fineout-Overholt, E. (2011). Evidence-Based Practice in Nursing & Healthcare (2nd ed.). Baltimore, MD: Wolters Kluwer Health. (Melnyk & Fineout-Overholt 2011) Pike, K.E., Savage, G., Villemagne, V.L., Ng, S., Moss, S.A. Maruff, P., ……. Rowe, C.C. (2007). β-amyloid (Aβ) Imaging and Memory in Non-Demented Individuals: Evidence for Preclinical Alzheimer’s Disease. Brain, 130, 2837-2844. http://brain.oxfordjournals.org/content/130/11/2837.full.pdf+html. Read More