My Alzheimer's Journey

Part 16 - The Link Between Depression and Alzheimer's Disease

Yesterday, I wrote about the high percentage of Alzheimer’s patients who suffer with depression. Between 40% and 50% of Alzheimer’s patients have been diagnosed with depression. This is a staggering number when only about 7 percent of the general population experiences depression.

Today, I want to share with you what I have learned about the link between depression and Alzheimer’s (AD). Researchers generally agree that depressive symptoms represent a risk factor for AD, whether they are an early symptom of neurodegeneration, or whether they are a reaction to early cognitive deficits.

What exactly is Major Depressive Disorder (MDD)?

MDD is diagnosed when an individual has a persistently low or depressed mood, anhedonia or decreased interest in pleasurable activities, feelings of guilt or worthlessness, lack of energy, poor concentration, appetite changes, psychomotor retardation or agitation, sleep disturbances, or suicidal thoughts.

Early studies found that the cause of MDD was mainly due to abnormalities in neurotransmitters, especially serotonin, norepinephrine, and dopamine. This research led to the treatment of MDD using different antidepressants such as selective serotonin receptor inhibitors, serotonin-norepinephrine receptor inhibitors, dopamine-norepinephrine receptor inhibitors.

More recent research has found that MDD is associated primarily with more complex neuroregulatory systems and neural circuits, causing secondary disturbances of neurotransmitter systems.

I have studied four leading research paths looking at the connection between MDD and AD:

• Chronic Stress

  In 2020, Ioannis Sotiropoulos, PhD, Medical School, University of Minho, Braga, Portugal, reported that his research shows that chronic depression related stress can activate AD-related mechanisms, such as damaging tau production function and increasing amyloid-beta production.

• Proteostasis Dysregulation

  Problems with how the body synthesizes and metabolizes proteins (proteostasis) is a key factor linking depression and inflammation, thereby contributing to AD risk, according to a study published in July 2025 in Nature Mental Health.

• Shared Genetic Factors

  A study published in January 2025 in Nature Mental Health supports previous evidence of the genetic overlap between depression and AD. In 2017, a report in Translational Psychiatry explained the findings of a large scale study that showed minor depression and major depression lie on a single genetic continuum. In other words, depression is heritable. Putting the puzzle pieces together, if depression is heritable and there is a genetic overlap between depression and AD, then the theory is that AD may be heritable for people diagnosed with MDD.

• Brain Structure Alterations

  A 2019 scientific review explained how neurobiological events, such as “neurodegeneration, cerebrovascular disease, and neuroinflammation result in a brain that is more vulnerable to the consequences of the pathophysiological features of AD, lowering the threshold for the onset of the behavioral presentation of AD (i.e., cognitive decline and dementia).” In other words, these three shared neurobiological features of depression and AD may cause the brain to lower the threshold for AD.

The University of Connecticut Center on Aging published a report in July 2025, that clearly explains the likely links between MDD and AD. Breno Diniz, MD, Ph.D., associate professor of psychiatry at UConn Health and the Center on Aging, points out that MDD is a “disease that is bigger than a depressed mood.” He goes on to say, “It has consequences that are silent, that may appear many years later.”

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