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.

Antidepressants in Alzheimer’s Disease: A Focus on the Role of Mirtazapine

“…Indeed, depression in elderly patients can also be considered a sign or a risk factor for the development of dementia, requiring a careful assessment of the patient condition, since the diagnosis of these diseases is very challenging. In early AD, depression symptoms generally translate into a sadder mood and depressive thoughts, while in more advanced states, problems with agitation, aggression and circadian rhythm alterations are more evident [ 5 ]. Another important finding is the fact that about a third of adults who have depression are also diagnosed with mild cognitive impairment (MCI), which precedes severe forms of AD [ 30 ].…”

“…Once again, mirtazapine was not effective in the treatment of sleep disorders (regarding the duration and quality of nighttime sleep), increasing the daytime sleepiness [ 117 ]. Moreover, another recent investigation (based on the collection of opinions from experts in the field) demonstrated that in patients with AD and depression, one of the antidepressants of choice is mirtazapine, characterized by having a dual mechanism of action and by leading to improvements in cognitive function/depressive episodes [ 5 ]. Furthermore, a systematic review and network meta-analysis concluded that sertraline and mirtazapine improved depressive symptoms, with no differences in cognitive function.…”

“…Thus, although several contradictory and unclear information, mirtazapine is still widely prescribed for depression in AD patients [ 5 ]. However, a careful and individualized examination of the patient is needed, as well as more studies about this drug in the context of AD-associated depression.…”

“…However, in general, selective serotonin reuptake inhibitor drugs (SSRIs) are the best tolerated in this context, due to their efficacy with less associated side effects [ 2 ]. Even so, other drugs that have a dual mechanism of action are, also, often prescribed to these patients, such as mirtazapine [ 5 ].…”

Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer’s Disease

“…Alzheimer’s disease is also accompanied by neuropsychiatric symptoms, including depression [ 68 ]. According to the meta-analysis of recent studies, up to 16% of AD patients exhibited major depression [ 69 ]. AD increases the severity of depression, which in turn induces cognitive impairments [ 70 ].…”