Distinguishing late-life depression and Alzheimer's disease based on memory impairment and memory-associated biochemical markers - a systematic review

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  • Daniel Kjærgaard
  • Jesper Mogensen
Background: The need to identify Alzheimer’s disease and late-life depression increases as the overall age of the population rises. The lack of evidence of the underlying physiopathologies as well as the heterogeneity of both illnesses complicate the distinction, thus increasing the risk of misdiagnosis. Providing the appropriate diagnoses are necessary to ensure the best possible outcome of care and treatment of existing and future treatment. This systematic review examines the role of episodic memory impairment and memory-associated biochemical markers to distinguish between late-life depression and Alzheimer’s disease. Method: 78 articles were included for full-text screening, of which 9 met the inclusion criteria. These criteria are that articles includes both participants with late-life depression and Alzheimer’s disease, examining impaired episodic memory and are peer-reviewed. Studies examining genes or having comorbid illnesses were not included. Results: Late-life depression and Alzheimer’s disease can both be characterized by hippocampal atrophy which consequently can lead to impairment of episodic memory (especially coding new information) and changes in memory-associated biochemical markers. Indeed, measures of cerebrospinal fluid (p-tau231, AβxMAP&t-tau/Aβ40, Aβ1-40/1-42, D-serine and Neprilysin) and urinary samples (AD7c-NTP) are able to distinguish between the two illnesses with a sensitivity and specificity ~80%. Neuropsychological tests (FCSRT, OI) have approximately the same accuracy. Yet, also reflected in the reviewed papers is the fact that late-life depression is not a homogeneous diagnosis, thus subtypes might be particularly difficult to differentiate from Alzheimer’s disease. Furthermore, the possibility that subtypes of late-life depression are prodromes to Alzheimer’s disease is a pressing issue questioning whether the differentiation is even possible. Conclusion: Measures of memory impairment can be valid means to distinguish late-life depression from Alzheimer’s disease. Both diagnoses can be characterized by impairment of episodic memory, indeed, the degree of the impairment is what can help set the diagnosis. Future studies should study the underlying pathophysiology of both diagnoses, and understand the possible causal relationship between them, to set a more certain diagnosis.
Original languageEnglish
JournalEC Neurology
Volume12
Issue number3
Pages (from-to)1-26
Publication statusPublished - 2020

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