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

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.

Pre-Diagnostic Manifestations of Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Longitudinal Studies

“…Conversely, a Finnish register-based study with up to 33 years of follow-up found no association between anxiety and AD with neither 5 nor 10 years interval between diagnoses (Tapiainen et al, 2017). Another study from the UK with up to 27 years follow-up was not able to find an association between anxiety and AD (Bature et al, 2018).…”

“…One study looking at both British and French routine data found evidence of association between malaise and fatigue with future AD diagnosis within 2 (OR UK = 1.36; 95% CI: 1.17 to 1.58 | OR Fr = 1.78; 95% CI: 1.59 to 2.0) and 2-10 years (OR UK = 1.23; 95% CI: 1.08 to 1.39 | OR Fr = 1.59; 95% CI: 1.36 to 1.86). They also found Syncope and collapse to be more common prior to AD diagnosis within 2 years (OR UK = 1.95; 95% CI: 1.53 to 2.48 | OR Fr = 2.49; 95% CI: 1.68 to 3.69) and 2-10 years (OR UK = 1.23; 95% CI: 1.01 to 1.5 | OR Fr = 1.57; 95% CI: 1.06 to 2.34) (Bature et al, 2018).…”

“…We identified five longitudinal studies conducted in the UK, US, France and South Korea looking at sensory symptoms reported prior to the diagnosis of AD (Table 1). Sample sizes ranged from 109 (Bature et al, 2018) to 40,428 (Nedelec et al, 2022) and total follow-up periods ranged from 10 (Kim et al, 2023a) to 27 (Bature et al, 2018) years. All five studies used medical records to ascertain symptoms.…”

“…French primary care data showed similar associations for constipation within 2 years before AD diagnosis (OR= 1.66; 95% CI: 1.47 to 1.87) and 2-10 years before (OR=1.59; 95% CI: 1.33 to 1.89) (Nedelec et al, 2022). However, a small study using UK primary care data did not replicate these results for constipation (Bature, 2018).…”

Expression of the Tau Protein and Amyloid Protein Precursor Processing Genes in the CA3 Area of the Hippocampus in the Ischemic Model of Alzheimer’s Disease in the Rat

“…The hippocampus is an important part of the brain due to its anatomical structure and physiological functions, especially in the area related to learning and memory under normal conditions and dementia in Alzheimer's disease and brain injury after ischemia [1][2][3][4][5][6][7]. The hippocampus plays an important role in the consolidation of information from short-term memory to long-term memory and spatial orientation, and this important transmission is disturbed inter alia in Alzheimer's disease [3,4]. In addition, various areas of pyramidal neurons in the hippocampus also show a rather specialized response to pathological factors, as exemplified by similar neurodegenerative changes in Alzheimer's disease and cerebral ischemia [5,[8][9][10].…”