Identifying patterns in signs and symptoms preceding the clinical diagnosis of Alzheimer’s disease

A thesis submitted to the University of Bedfordshire in partial fulfilment of the requirements for the degree of Doctor of PhilosophyPrevious research indicates that there is a major challenge caused by the late diagnosis of Alzheimer’s disease (AD), with no suitable diagnostic tool available for use in primary care. Aim: This research is aimed at identifying patterns in the early signs and symptoms of AD to suggest the development of a predictive model for the early detection of AD. Objectives: To; a) map, synthesise and appraise the quality of existing literature on the signs and symptoms preceding the diagnosis of AD via the systematic scoping review of the literature; b) identify patterns in signs and symptoms preceding the clinical diagnosis of AD in general practices via a retrospective medical record review study (RMRRS); c) explore the clinicians perspectives regarding the early signs and symptoms, issues surrounding the late diagnosis and collect recommendations for overcoming barriers to timely detection of AD via a semi-structured interview. Methods: This was a mixed method research comprising a systematic scoping review of literature from 1937-2016, undertaken using the descriptive analysis on the sequence and the timing of signs and symptoms preceding the diagnosis of AD. Methodological quality of studies was assessed with the QUADAS-2 tool as well as PRISMA guidelines and descriptive analysis followed. A RMRRS followed using the logistic regression analysis and a semi-structured interview of general practitioners (GPs) in Milton Keynes (MK) and Luton, using the framework analysis. Results: The findings from the review suggest that neurological and depressive behaviours are an early occurrence in early-onset AD with depressive and cognitive symptoms in the measure of semantic memory and conceptual formation in late-onset AD. It appears that there is a big variation in the patterns of signs and symptoms with cases of misdiagnosis. However, there was limited evidence due to the limited number of studies of this kind. The nested case control design of 109 samples indicates that auditory disturbances could have diagnostic value, with a range of signs and symptoms that appears at different time. While the interviews highlight and confirm areas for consideration in the primary care and NHS. Additionally, the study reports practices in relation to the early diagnosis of AD. However, the result is not an overall representation of the views of GPs. Conclusion: Findings suggest that individuals with auditory disturbances have increased odds of AD. This was more striking in the white female population, with borderline significance due to limited data that is too small to detect such an uncommon symptom(s)

Signs and symptoms preceding the diagnosis of Alzheimer’s disease: a systematic scoping review of literature from 1937 to 2016

Objective Late diagnosis of Alzheimer’s disease (AD) may be due to diagnostic uncertainties. We aimed to determine the sequence and timing of the appearance of established early signs and symptoms in people who are subsequently diagnosed with AD. Methods We used systematic review methodology to investigate the existing literature. Articles were reviewed in May 2016, using the following databases: MEDLINE, PsycINFO, CINAHL, British Nursing Index, PubMed central and the Cochrane library, with no language restriction. Data from the included articles were extracted independently by two authors and quality assessment was undertaken with the quality assessment and diagnostic accuracy tool-2 (QUADAS tool-2 quality assessment tool). Results We found that depression and cognitive impairment were the first symptoms to appear in 98.5% and 99.1% of individuals in a study with late-onset AD (LOAD) and 9% and 80%, respectively, in early-onset AD (EOAD). Memory loss presented early and was experienced 12 years before the clinically defined AD dementia in the LOAD. However, the rapidly progressive late-onset AD presented predominantly with 35 non-established focal symptoms and signs including myoclonus (75%), disturbed gait (66%) and rigidity. These were misdiagnosed as symptoms of Creutzfeldt-Jacob disease (CJD) in all the cases. The participant with the lowest mini-mental state examination score of 25 remained stable for 2 years, which is consistent with the score of the healthy family members. Conclusions The findings of this review suggest that neurological and depressive behaviours are an early occurrence in EOAD with depressive and cognitive symptoms in the measure of semantic memory and conceptual formation in LOAD. Misdiagnosis of rapidly progressive AD as CJD and the familial memory score can be confounding factors while establishing a diagnosis. However, the study was limited by the fact that each one of the findings was based on a single study. * Alzheimer's disease (AD) * systematic scoping review * early signs and symptoms * mild cognitive impairment (MCI) * early stage of A

Retrospective medical record research: Reflections of a unsponsored researcher.

This article is a reflective narrative by the author following the successful completion of a doctoral thesis involving the analysis of primary care data. The aim of the study was to identify patterns in signs and symptoms preceding a clinical diagnosis of Alzheimer’s Disease (AD). Here, we discuss the challenges of conducting research using the patient medical health records as a non-sponsored researcher. The narrative explores the experiences of undertaking practice recruitment, issues that arose around access to data and the requirement for stakeholder commitment, with proposals for other similar projects that attempt to undertake research using patients’ data. The Gibbs reflective cycle was adopted in this narrative. This model encourages a clear description of events, analysis of personal feelings, evaluation of the experience, conclusions as to the options that were considered and actions to take if faced with the same study methods (involving primary care practitioners and/or the review of patient records). It also allows a structured reflection while simultaneously discussing the barriers and facilitators to undertaking a retrospective medical record research. The researcher also proposes some recommendation(s) to overcoming barriers to recruitment in primary care

Identifying patterns in signs and symptoms preceding the clinical diagnosis of Alzheimer's disease : retrospective medical record review study and a nested case -control design

OBJECTIVE: Evidence suggests that individuals with Alzheimer's disease (AD) are often diagnosed in the later stages of their disease with a poor prognosis. This study aimed to identify patterns in signs and symptoms preceding the clinical diagnosis of AD to suggest a predictive model for earlier diagnosis of the disease in the primary care. DESIGN: A retrospective medical record review; nested case control design. PARTICIPANTS: Participants included one hundred and nine patients from three general practice (GP) surgeries in Milton Keynes and Luton Clinical Commissioning groups (CCG) (37 cases with AD and 72 controls without AD). MAIN OUTCOME MEASURE: A retrospective analysis using the logistic regression of the presence of signs and symptoms before the diagnosis of AD was attained. Identification of the timing and sequence of appearance of these presentations as first reported before the clinical diagnosis was measured. RESULT: Episodic memory with an odds ratio of 1.85 was the most frequent presentation, documented in 1.38% of the controls and 75.6% in cases. Auditory disturbance with an odds ratio of 3.03, which has not previously been noted except in the form of auditory hallucination, could have a diagnostic value. CONCLUSION: Auditory disturbance, which occurred mostly in the Caucasian females, could discriminate individuals with AD from those without. The symptom, which presented up to 14.5 (mean time) years prior to clinical diagnosis, was identified in Caucasians and mixed race individuals only