Dementia: What’s the link between depression and memory decline?

Viewing the two conditions as two sides of the same coin suggests new hope for those living with depression, memory loss, or both.

David Merrill, MD, PhD, director of the Brain Health Center at the Pacific Neuroscience Institute, CA, not involved in the study, told MNT that prior to this study, researchers had looked at depression and memory loss independently, “trying to parse them apart as though they’re separate.”

But Merrill noted it has long been understood that memory and mood are strongly linked.

“If you’re studying memory, you need to control for mood,” Merrill said. “The substrate of the creation of both phenomena is coming out of the same thing,” he added, noting the similarities between depression and dementia.

Merrill said the activity in the prefrontal cortex and hippocampus are similar in both conditions. When there’s a decrease in frontal lobe activity — as is seen with depression — there is a reduced ability to hold things in working memory, Merrill explained.

“The circuitry and the cells and the synapses involved in memory formation have a profound overlap with the circuitry involved in moods, mood regulation, and mood formation,” Merrill said.

Cadar explained that depression and memory have chemistry in common, including the “dysregulation of neurotransmitters, such as serotonin, norepinephrine, and dopamine, which play crucial roles in mood regulation and cognitive abilities.”

“In depression, the imbalance of these neurotransmitters can impair synaptic plasticity, which is essential for learning and memory formation,” Cadar said. “Serotonin is involved in the modulation of mood and cognition, and its deficit can lead to reduced neurogenesis in the hippocampus, a brain region critical for memory consolidation.”

The growth and survival of neurons in the hippocampus, Cadar continued, can also be threatened by high cortisol levels that often accompany depression.

“Prolonged exposure to high cortisol levels can lead to hippocampal atrophy, which is already commonly observed in older individuals with major depressive disorder,” Cadar said, adding that harmful inflammatory responses may result from depression.

“Depression is associated with increased levels of pro-inflammatory cytokines… that can alter neurotransmitter metabolism, reduce synaptic plasticity, and damage brain structures involved in memory such as the hippocampus and prefrontal cortex. Inflammation-induced neurotoxicity can, therefore, contribute to cognitive deficits observed in depressed individuals.”

— Dorina Cadar, PhD, senior study investigator

Finally, depression — especially in older people — can cause insomnia, depriving the brain of the critical memory consolidation that occurs in deep sleep, Cadar noted.

Dementia may cause mood and behavioral changes, while depression may lead to forgetfulness, which may cause some confusion around these two very distinct — albeit related — conditions.

“Depression, has historically been called ‘pseudo dementia’ in older adults, as it’s been appreciated as sort of a reversible cause of dementia,” Merrill said.

Unlike neurodegenerative dementia, which involves the irreversible death of brain cells, “pseudo dementia” stems from depression that causes brain cells to be less active. In depression, less active brain cells could still be reactivated.

“The decrease in brain activity [that occurs with depression] really leads to decreased capacity to form memories,” Merrill said.

In addition to all the physiological factors, when a experiences loss in memory capacity, Cadar noted “this cognitive impairment can lead to increased frustration, stress, and feelings of isolation.”

“These can trigger or exacerbate depressive symptoms and associated loneliness that is equally detrimental for mental abilities,” Cadar said.

The findings of this study, have “significant implications for future treatment approaches for both conditions and highlighting the need for integrated treatment approaches rather than treating them in isolation,” Cadar said.

Treatment might address both conditions simultaneously, and healthcare providers might develop new early screening programs that monitor older people for both mood and memory.

Merrill noted this would require a new interdisciplinary approach, bringing together psychologists and neurologists.

For now, Merrill said it’s imperative for the individual to aim to change one aspect of their mindset, given the nature of depression, if they hope to feel happier and restore memory function. “The problem is depression really robs you of motivation,” he added.

According to Merrill, physical activity may be the best course of treatment for both conditions. “Exercise is probably the best single intervention for the aging body and the aging brain,” he said.

Merrill proposed a future therapy that could involve consulting with your doctor and getting a prescription for physical therapy (PT). This could provide a helpful structure from which to begin digging your way out of depression while also improving memory.

“You have a scheduled appointment with the therapist and you have a trainer who’s happy to see you. All those things are just really activating,” he envisioned.

The value of this plan, Merrill said, goes beyond the body and brain health benefits. “You develop friendships, and you develop relationships and bonds. A huge part of depression is this social isolation of losing connectedness,” he noted.