Towards an understanding of the pathological basis of senile depression and incident dementia: Implications for treatment

Abstract

Senile depression (SD) is a heterogeneous syndrome. Several clinical profiles are more likely to appear in SD than in early-life depression, but it remains unclear whether the pathophysiology is different. The prevalence of dementia increases with aging, and the underlying pathophysiological processes in the preclinical phase begin even before cognitive deficits or neurological signs appear. SD may be either a risk factor for developing dementia or a prodromal stage of dementia. The inconsistent findings regarding the association between SD and incident dementia may be attributable to the neuropathological heterogeneity underlying SD. Most studies have focused on patients with the clinical diagnosis of Alzheimer disease (AD) as an outcome, but several clinicopathological studies suggest that primary age-related tauopathy and argyrophilic grain disease may account for a proportion of cases clinically misdiagnosed as AD in the elderly population. Furthermore, most AD cases have additional neuropathologic changes such as cerebrovascular disease and Lewy body disease. Here, we review the neuropathological findings linking SD to incident dementia, focusing on common age-related neuropathologies. In particular, the roles of disturbance of neural circuity, imbalance of monoaminergic systems, dysregulation of the hypothalamic-pituitary-adrenal axis, and elevated neuroinflammatory status are discussed. Finally, we review the current treatment of SD in the context of agerelated neuropathological changes.

Temporal trajectories of proposed biomarkers in psychiatric‐onset prodromal dementia with Lewy bodies: a case report

“…This approach based on the specific pathological basis of senile depression may also provide opportunity toward an understanding of its relation to incident dementia. 6…”

“…In terms of the differences in prognosis and management, further longitudinal studies are warranted to determine useful markers to predict conversion to DLB in patients with late‐onset depression. This approach based on the specific pathological basis of senile depression may also provide opportunity toward an understanding of its relation to incident dementia 6 …”

Case Report: Depression × dementia with Lewy bodies in the elderly: The importance of differential diagnosis

“…Depression in elderly people, diagnosed as senile depression (SD), includes heterogeneous symptoms and clinical profile findings. The pathophysiology remains unclear because it should be different ( 7 ). SD may be risk factor for developing dementia or a prodromal stage.…”

“…SD may be risk factor for developing dementia or a prodromal stage. Disturbance of neural circuity, imbalance of monoaminergic systems, dysregulation of the hypothalamic–pituitary–adrenal axis, and elevated neuroinflammatory status where studied and are involved with the syndrome ( 7 ). A very recent Guideline from Japanese Society of Mood disorders ( 8 ) (2022) of diagnosis and treatment of SD emphasizes the need of differential diagnosis from bipolar disorders, organic brain diseases, drug effects and dementia.…”

Electroconvulsive therapy as a potential therapeutic option in psychiatric‐onset prodromal dementia with Lewy bodies

“…Herein, we present a patient with psychiatriconset DLB that underwent ECT after a 10-month drug treatment for psychiatric symptoms, 2 and discuss the role of ECT in the management of psychiatric-onset DLB in terms of vulnerability of motor function. 3 Written informed consent was obtained from the patient.…”