Featuring Dr. Roger McIntyre, MD
Dr. Roger McIntyre is Professor of Psychiatry and Pharmacology at the University of Toronto and Head of the Mood Disorders Psychopharmacology Unit at the University Health Network in Toronto. He is also Executive Director of the Brain and Cognition Discovery Foundation and a director of the Depression and Bipolar Support Alliance (DBSA). Dr. McIntyre was named one of “The World’s Most Influential Scientific Minds” by Clarivate Analytics/Thomson Reuters (2014–2017), has published more than 400 articles and manuscripts, and has edited or co-edited numerous textbooks on mood disorders. He completed his medical degree at Dalhousie University and his psychiatry residency and fellowship in psychiatric pharmacology at the University of Toronto.
In this episode, we tackle a question so many of us in the 50+ community face: is forgetfulness just normal aging, or is it something more? Dr. McIntyre walks us through how bipolar disorder uniquely presents after 50, how to tell it apart from early dementia, and the cutting-edge research he’s leading to help us stay sharp.
Can bipolar disorder actually start after 50, or is it always something people are diagnosed with when they’re young?
Most people who live with bipolar disorder — roughly 75 to 85% — are diagnosed before age 25. But there’s replicated evidence that close to 10% (or more, depending on the study) experience their very first episode after age 50. These aren’t people who had it at 20 and are simply older now — for these patients, there was no prior evidence of the illness at all before it emerged later in life. Dr. McIntyre notes the clinical term for this, “old age bipolar disorder,” is an unfortunate name, but the phenomenon itself is real and well documented.
Is the biological cause different for someone diagnosed at 55 versus someone diagnosed at 20?
Significantly so. The single best predictor of whether a person with depression will go on to develop bipolar disorder is family history — and people whose bipolar onset happens after 50 are far less likely to have that family history than those diagnosed young. Instead, later-onset bipolar disorder is more strongly linked to vascular health problems — a higher rate of strokes and TIAs (mini-strokes), along with more vascular disease visible on brain MRIs. This points to a smaller genetic contribution and a larger role for vascular changes in the brain triggering illness later in life.
How does menopause or hormonal change factor into this, and into age-related brain fog generally?
In a big way. For some women, the menopausal transition is the first time bipolar disorder ever declares itself, and it’s also a known time of heightened risk of recurrence for women already diagnosed. Part of the mechanism ties back to sleep: falling estrogen levels affect a cluster of brain cells in the hypothalamus (the body’s rhythm center) that normally keep arousal in check — when estrogen drops, those cells can become overactive, disrupting sleep. Since bipolar disorder is fundamentally a disease of cycling and rhythm, poor sleep can directly precipitate mania or depression. Women with bipolar disorder also have higher rates of obesity, type 2 diabetes, and metabolic liver disease — conditions that tend to hit even harder as women age.
Mania in older adults often looks like agitation or anger rather than the classic euphoria we associate with younger patients. Why, and how do physicians tell the difference?
When bipolar disorder first appears later in life, mania tends to show up as restlessness, irritability, and a pervasive sense of gloom or doom — often with a notably high rate of reported suicidality — rather than the classic elation, grandiosity, and impulsive spending most people picture. Dr. McIntyre calls this the “mixed” presentation, and he’s seen it firsthand diagnosing bipolar disorder for the very first time in nursing home patients in their 60s and 70s who’d spent years being treated only for “agitation.” Because this presentation doesn’t fit the textbook picture, it’s frequently mistaken for depression, anxiety, or early dementia — and he notes that clinicians worldwide are seeing this irritable, agitated pattern more often than the classic euphoric mania that was more common earlier in his career.
With so many older patients dealing with type 2 diabetes and heart disease, how do GLP-1 drugs like Tirzepatide and Semaglutide fit into treating mental health?
GLP-1s currently carry six FDA-approved indications — obesity, diabetes, metabolic liver disease, obstructive sleep apnea, progressive kidney disease, and cardiovascular mortality — all conditions that occur at higher rates in people with bipolar disorder. Beyond treating those overlapping physical conditions, researchers are actively investigating whether GLP-1s can help treat or prevent mood episodes themselves, reduce substance and alcohol misuse (bipolar disorder has the highest rate of alcohol/substance misuse of any mental illness), and slow cognitive decline. A next-generation dual agonist, retatrutide, is now in Phase 3 trials specifically as a mood stabilizer for bipolar disorder, with results expected in the next one to two years.
Chronic inflammation is a hot topic in anti-aging conversations right now. Does it affect the brain’s stability as we get older?
es — there’s even a term for it: “inflammaging,” reflecting that inflammation is both a cause and a consequence of aging. In bipolar disorder specifically, there’s molecular evidence of premature cellular aging, and the condition is associated with a shorter “health span” — meaning conditions typically seen in a 50- or 60-year-old often show up in bipolar patients by their 20s and 30s, and dementia can occur both more frequently and earlier. The encouraging news: with timely, accurate diagnosis and treatment, much of this process can be slowed or reversed — this isn’t a life sentence.
Many older adults are on multiple medications. How does that polypharmacy affect cognitive clarity?
Considerably, and often in preventable ways. Dr. McIntyre points to research on anticholinergic drugs (found in many common cold, cough, and prescription medications) showing that stopping them produced a significant improvement in cognitive function. He’s found some of his biggest treatment wins come not from adding a new medication, but from removing ones a patient doesn’t actually need — particularly sedating drugs like benzodiazepines, which can also affect balance and increase fall risk. He recently co-authored a formal de-prescribing guideline on behalf of the American Society of Clinical Psychopharmacology (ASCP): the goal isn’t zero medications, it’s making sure every medication a patient takes actually makes sense together.
What about ketamine? It’s been in the news, including a high-profile overdose death.
Ketamine has been genuinely transformative for treating bipolar depression, particularly when it comes with heavy irritability, agitation, and anxiety. It’s been shown to be safe and well-tolerated in clinical settings (including in patients 65 and older), works rapidly, and does not appear to trigger mania or psychosis. Dr. McIntyre and colleagues recently published research in JAMA showing it can rapidly reduce suicidal thinking within hours to a day. He’s careful to distinguish the therapeutic, medically supervised use of ketamine (including the FDA-approved intranasal formulation Spravato, though that’s approved for depression, not bipolar) from the tragic, unsupervised misuse that makes headlines.
How can someone — or their physician — tell the difference between bipolar-related memory issues and the early signs of Alzheimer’s?
The key differences are speed and pace. Cognitive decline related to bipolar disorder is real, but it tends to be slower and more insidious. Alzheimer’s and other major neurocognitive disorders, while also gradual, tend to progress more rapidly once they manifest. Family history and the specific pattern of cognitive impairment both factor into the distinction as well.
Beyond managing mood swings, how can older adults regain mental sharpness and productivity?
Social engagement matters enormously — loneliness and isolation, which become more common as we age, can accelerate cognitive decline, while connection (to people, animals, art, nature, or community) helps protect against it. Beyond that, it comes down to the fundamentals: exercise, an affordable and sustainable diet, and adequate sleep. Dr. McIntyre’s broader philosophy is to manage patients “above the neck and below the neck” — treating the mood disorder itself while also making sure conditions like diabetes, thyroid function, and weight are under control, since an estimated 40–50% of people with bipolar disorder have undiagnosed metabolic liver disease that can itself affect cognition.
Watch the full interview here:https://youtu.be/7YDsq2iyaIU
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