Every morning, two Google news alerts announce themselves as they land in my inbox.
Ping. Depression.
Ping. Dementia.
Their arrival invariably sounds more cheerful than the news either brings.
My depression alert — like my encounter with the illness — predates the one for dementia and is a daily reminder of a once all-consuming quest to find a treatment that worked for my mother, Lala. The one for dementia? No cure for that, but it helped me to understand the manifest symptoms. Why did Mum hallucinate? Why couldn’t she taste anything? Why had she forgotten me? And could I do anything to avoid the same fate?
These two devastating conditions aren’t linked only in my news feed. Over the years, scientific studies twin them again and again, and my overflowing email folders bear testimony to a cementing of the relationship. The latest research is a comprehensive study by a team at Nottingham University that examined data from nine meta-analyses and included nearly 3.5 million people and more than 284,000 dementia cases.
Rowan with her mother and brother in Kenya, 1970
ANTHEA ROWAN
By focusing on when the depression was measured — in midlife or in later life — “we showed that both periods increase dementia risk, with late-life depression linked to a 95 per cent higher risk and midlife depression a 56 per cent higher risk”, the lead author, Jacob Brain, a PhD researcher in medicine, told me.
• Depression found to increase memory loss … and vice versa
Mum’s depressions started in her thirties. How much of a role did they play in the dementia that revealed itself in her seventies? There are several compelling hypotheses that suggest one drives the other.
My mother’s incessant worrying — “rumination” in medical jargon — would have caused a surge in the production of the stress hormone cortisol. And over time, high cortisol levels damage the hippocampus, which is key for memory and learning, says Dorina Cadar at the Centre for Dementia Studies at Brighton and Sussex Medical School, who recently co-authored a study on the bidirectional links between depression and dementia.
The hippocampus — from the Greek hippos for “horse” and kampos for “sea monster” — is the seahorse-shaped memory vault that serves as a compass for our spatial awareness and a cache for our life’s stories. First Mum forgot how to find the bathroom. And then she forgot me.
Cadar says it’s long established that memory loss can lead to depression. After all, as she observes, and as I observed in my mother, losing a sense of self and independence is distressing.
Rowan’s mother developed dementia in her seventies
ANTHEA ROWAN
“However,” she says, “we found that depressive symptoms are not only linked to worse memory performance at the start, they also predict faster memory decline later. There’s a bidirectional loop: depression contributes to memory decline and memory decline worsens depression, which is also linked to increased inflammation in the body, which can impact the brain. This low-grade chronic inflammation has been associated with faster cognitive ageing and a higher risk of diseases like Alzheimer’s.” Hence the contemporary coining of the term “inflammageing”.
Depression has also been shown to hinder the production of important brain-derived neurotrophic factors (BDNF). Think of BDNF as the brain’s fertiliser, imperative for the healthy growth and repair of neurones (nerve cells). Suicide victims have been found to have decreased levels.
• ‘They thought Dad was depressed. It was rare type of dementia’
And then there’s the theory posited by the Nottingham team, that depression compromises healthy blood flow in the brain. Was that what caused my mother’s stroke at 75? A depression that lasted for more than two years? Or was it, as my mother’s neurologist offered when I pressed him for an explanation, simply that she sat too still for too long? After all, in the absence of the usual stroke suspects of high cholesterol, arrhythmia and high blood pressure, what else could have caused the clot that lodged itself in her left occipital lobe?
The stroke robbed her of the ability to read by causing the rare condition pure alexia. And without her voracious reading habit, which had shored her up against the worst of her depressions, Mum’s cognitive reserve, that dam of precious saved-for-later intellect, drained away fast.
If depression was the first nudge on a row of fateful dominoes, it was probably because its effects are cumulative. One study found a 13 per cent increase in dementia risk for every episode of depression; another concluded that while the illness is a risk factor for dementia later, recurring depression is “particularly pernicious” — two or more episodes doubles the risk.
Rowan with her mother in Kenya, 1966
ANTHEA ROWAN
A memory: I have accompanied Mum to yet another psychiatric appointment in yet another attempt to find something — anything — that might help. Mum is mired in the two-year episode that preceded the stroke that preceded dementia. See what I mean? Catastrophic cumulative collapse: a first slice of mortar worried loose, a first clue of a home falling apart, then an avalanche of bricks that buried Mum under rubble.
My mother was so anxious about her appointment that she begged me beforehand to do the talking. So I explained, again, when the depressions started — yes, before my father died — and how long they lasted. Yes, I say, we’ve tried this, we’ve tried that: ECT, lithium, CBT.
“How many of these episodes has she had?” the doctor, who has given up trying to get answers out of Mum, asks me. “Three, four?”
Mum gasps, and speaks for the first time during the consultation, “God, no! Dozens. I’ve had dozens of them.”
A long time later my sister and I will calculate that Mum lost a quarter of her life to depression. Twenty years, perhaps more.
But it’s not only the direct physiological effects of depression that we need to consider: “There are behavioural consequences too,” Cadar says, and these have an indirect physiological impact. Depression disrupts sleep, for example. Mum lay awake, night after night, for months, or woke in the small hours and was unable to drop off again.
It is during deep restorative non-rapid eye movement sleep that the brain sets about its housekeeping. It doesn’t only play and replay our memories, transcribing them to invisible archives with invisible, indelible ink in a process scientists call “memory consolidation” — it cleans up between those archives too. In deep restorative sleep, cerebrospinal fluid flows freely, rinsing waste from the brain, its weight in waste every year about 3lb, including toxic beta-amyloid and tau tangles, the signature stains of Alzheimer’s disease.
But it’s not just the right kind of sleep that affects the brain, it’s how peaceful that sleep is. Dr Abidemi Otaiku, a neuroscientist at Imperial College London, recently led research with the UK Dementia Research Institute, which found children and adults who suffered frequent nightmares were more likely to die before 70 than people who didn’t.
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It’s possible, Otaiku tells me, that nightmares lead to faster aging because of “the release of stress hormones like cortisol”. That inflammageing again, and its impact on body and brain.
“My previous studies,” he continues, “showed that people who have more frequent nightmares in childhood, middle age or older age may experience faster cognitive decline and may be more likely to develop cognitive impairment or dementia later in life.”
In the last years of her life Mum began to suffer a recurring nightmare. She was trapped on a ship. Sometimes she’d describe her distressing dream over breakfast. “I was on a ship,” she’d say, “I couldn’t get off. I was so afraid. I didn’t know where you were.”
I ask Otaiku if it was the nightmares exacerbating Mum’s dementia, or dementia the nightmares. The link is interesting, he says, and either could be true: nightmares can be an early sign of dementia, but also “it is plausible that they may hasten it”. Whatever the case, the nightmare of dementia became part of our days.
I once asked Mum what depression feels like. “Like living behind glass,” she told me. A perfect descriptor of the cold isolation the illness brings.
If you look to the Lancet’s list of modifiable risks for dementia, you’ll find poor sleep, lack of exercise and social isolation. You’ll also find depression: 3 per cent of all dementia cases are attributable to the illness.
Professor Gill Livingston, lead author of the Lancet’s list, offers a small reassuring caveat: while depression “really increases the risk of dementia, it seems that this is only for people who remain untreated or do not get better”.
Worryingly, though, Paul Keedwell, a fellow of the Royal College of Psychiatrists who works at Re:cognition Health and who developed a liaison service where GPs could access specialist psychiatric advice, says the incidence and prevalence of major depression and other mental health illnesses in the UK has risen over the past decade, influenced by socioeconomic factors and the pandemic.
But on a hopeful note, treatments in primary care — especially psychological treatments — have improved, he says. “This means that depression is being diagnosed earlier, and the earlier it is treated, the better. Your GP is still the best place to start.”
Also, he adds, there’s a growing repertoire of pharmacological and neuromodulatory treatments, so the prognosis for depression is improving. “But treatment-resistant depression remains a significant challenge, and demand for treatment is increasing.”
Professor Craig Ritchie, at Scottish Brain Sciences, is at pains to point out that a handful of depressive episodes are unlikely to have a lasting impact on a brain. “We’re talking about ‘chronic exposure’,” he says, for it takes years for the body’s natural resilience to be overwhelmed — years of the brain being “steeped” in stress, “just like it takes years of eating badly, years of sugar overload, to expose a person to the risk of type 2 diabetes”.
The Nottingham team’s findings endorse the importance of identifying and treating depression at any stage of life because, as Livingston says, “many fewer people would develop dementia if their depression was helped”. And, as Cadar says, addressing depression early may protect memory, and protecting memory may protect mental health.
Hand in hand, see.
If years of my mother’s life had not been lost to depression, I believe we would not have lost her to dementia.