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

Abstract

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 is 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 disease. The symptom, which presented up to 14.5 (mean time) years prior to clinical diagnosis, was identified in Caucasians and mixed race individuals only. Strengths: The study demonstrates that auditory disturbance could allow an earlier diagnosis of AD in Caucasian females. Episodic memory was confirmed as being frequently noted in AD patients prior to a clinical diagnosis as per previous publications. This study supports the development of a scoring system for the earlier diagnosis of AD. The data used was free from the confounding effects of misinformation, as this was written at the point of collection, thereby benefitting from the use of GP data that is diversified, reliable and valid. Limitations: Limited sample size that will not allow for generalization of less frequent observations due to their low prevalence in case notes. Randomisation was not achieved; however, the best available nonrandomisation which is consecutive sampling was used. Patterns identified were in LOAD, the baseline could vary with other geographical areas.