Toggle Main Menu Toggle Search

Open Access padlockePrints

Neuropathology of Depression in Alzheimer's Disease: Current Knowledge and the Potential for New Treatments

Lookup NU author(s): Dr Ahmad Khundakar, Professor Alan ThomasORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Depression is among the most common behavioral and psychological symptoms of dementia, and leads to more rapid decline and higher mortality. Treatment for depression in dementia has centered on conventional antidepressant drug treatment based around the monoamine hypothesis of depression. However, recent major studies have suggested that conventional antidepressant treatments that aim to correct underlying deficits in monoamine neurotransmitters are not effective for depression in dementia. Postmortem studies have also suggested that depression in dementia does not arise from serotonergic or noradrenergic abnormalities, or indeed from the degenerative pathology associated with Alzheimer's disease. In contrast, considerable recent evidence has suggested that alterations in glutamatergic transmission may contribute to the pathophysiology of depression. This supports the view that treatment-resistant depressed patients, such as many dementia patients, may benefit from agents affecting glutamate transmission. This review will thus draw together the wealth of pathological data examining the basis of depression in Alzheimer's disease and relate this to current thinking on treatment, with the aim of generating discussion on potential novel therapeutic strategies.

Publication metadata

Author(s): Khundakar AA, Thomas AJ

Publication type: Article

Publication status: Published

Journal: Journal of Alzheimer's Disease

Year: 2015

Volume: 44

Issue: 1

Pages: 27-41

Online publication date: 10/09/2014

Acceptance date: 25/08/2014

Date deposited: 06/01/2016

ISSN (print): 1387-2877

ISSN (electronic): 1875-8908

Publisher: IOS Press


DOI: 10.3233/JAD-148003

PubMed id: 25208623


Altmetrics provided by Altmetric


Funder referenceFunder name
G0900652Medical Research Council
G1100540Medical Research Council
G0400074Medical Research Council
G0502157Medical Research Council
MR/L016451/1Medical Research Council