Depression in Alzheimer's Disease: A Delphi Consensus on Etiology, Risk Factors, and Clinical Management

Abstract

Background: Alzheimer's disease (AD) and other forms of dementia are among the most common causes of disability in the elderly. Dementia is often accompanied by depression, but specific diagnostic criteria and treatment approaches are still lacking. This study aimed to gather expert opinions on dementia and depressed patient management to reduce heterogeneity in everyday practice. Methods: Prospective, multicenter, 2-round Modified Delphi survey with 53 questions regarding risk factors (11), signs and symptoms (7), diagnosis (8), and treatment (27) of depression in dementia, with a particular focus on AD. The questionnaire was completed by a panel of 37 expert physicians in neurodegenerative diseases (19 neurologists, 17 psychiatrists, and 1 geriatrician). Results: Consensus was achieved in 40 (75.5%) of the items: agreement in 33 (62.3%) and disagreement in 7 (13.2%) of them. Among the most relevant findings, depression in the elderly was considered an early sign (prodromal) and/or a dementia risk factor, so routine cognitive check-ups in depressed patients should be adopted, aided by clinical scales and information from relatives. Careful interpretation of neuropsychological assessment must be carried out in patients with depression as it can undermine cognitive outcomes. As agreed, depression in early AD is characterized by somatic symptoms and can be differentiated from apathy by the presence of sadness, depressive thoughts and early-morning awakening. In later-phases, symptoms of depression would include sleep-wake cycle reversal, aggressive behavior, and agitation. Regardless of the stage of dementia, depression would accelerate its course, whereas antidepressants would have the opposite effect. Those that improve cognitive function and/or have a dual or multimodal mode of action were preferred: Duloxetine, venlafaxine/desvenlafaxine, vortioxetine, tianeptine, and mirtazapine. Although antidepressants may be less effective than in cognitively healthy patients, neither dosage nor treatment duration should differ. Anti-dementia cholinesterase inhibitors may have a synergistic effect with antidepressants. Exercise and psychological interventions should not be applied alone before any pharmacological treatment, yet they do play a part in improving depressive symptoms in demented patients. Conclusions: This study sheds light on several unresolved clinical challenges regarding depression in dementia patients. Further studies and specific recommendations for this comorbid patient population are still needed.

Keywords: Alzheimer's disease; cholinesterase inhibitors; consensus; dementia; depression; dual and multimodal antidepressants; precognitive action; prodromal symptoms.

Figure 1

Degree of consensus, agreement, and disagreement among all participants of the Delphi study. N = 53 statements.

Figure 2

Key messages of the study. Consensus was reached on several fundamental statements regarding the relationship between late-onset depression and subsequent dementia (A) and depression in older individuals already diagnosed with dementia (B). AD, Alzheimer's disease; ChEIs, cholinesterase inhibitors; CSDD, Cornell Scale for Depression in Dementia; FTD, frontotemporal dementia; PD, Parkinson's disease; SSRIs, selective serotonin reuptake inhibitor.