A widely used supplement for joint pain may be accelerating cognitive decline in people with Alzheimer's disease and related dementias. Researchers analyzing brain tissue and health records found that glucosamine, taken by approximately 6 to 7 percent of Americans over 70, could worsen dementia progression and increase mortality risk by 25 percent in people already diagnosed with the disease.

What Does Glucosamine Do to the Brain?

The study, published in Nature Metabolism, reveals that glucosamine may trigger a harmful process in the brain called hyperglycosylation. This process involves the buildup of carbohydrate molecules called glycans that attach to proteins and disrupt their normal function. In people with Alzheimer's disease, this accumulation becomes increasingly severe as the disease progresses.

Researchers examined post-mortem brain tissue from people with and without Alzheimer's disease and found that brains affected by Alzheimer's showed significantly higher production of glycans, particularly in regions responsible for memory and learning. When these glycans accumulate, they overload the brain's metabolic systems and disrupt critical communication between nerve cells, a process essential for forming new memories.

"Hyperglycosylation can greatly increase the brain burden of sugar molecules called N-glycans that overload metabolic processing and disrupt critical cellular processes like synaptic signaling in regions of the brain devoted to learning and making new memories," explained Harris A. Gelbard, MD, PhD, Director of the Center for Neurotherapeutics Discovery at the University of Rochester Medicine.

Harris A. Gelbard, MD, PhD, Director of the Center for Neurotherapeutics Discovery, University of Rochester Medicine

The accumulation of these molecules can trigger a destructive cycle: as glycans continue to build up, they destroy the connections between nerve cells and activate the immune system, creating ongoing brain damage.

How Did Researchers Test This Finding?

Scientists conducted experiments in mice genetically modified to develop two different forms of Alzheimer's disease. They observed the same patterns of hyperglycosylation seen in human brains, with the highest concentrations in memory and cognitive processing regions. When researchers blocked glycan formation in the mice, the animals performed significantly better on memory tests.

Because glucosamine can easily cross the blood-brain barrier and become incorporated into brain glycans, the team tested whether the supplement would worsen cognitive decline in mice. In mice with an aggressive form of Alzheimer's disease, glucosamine supplementation significantly increased glycan production and worsened social memory performance.

What Did the Study Find in People With Dementia?

To determine whether these effects occur in humans, researchers analyzed health records from more than 50,000 people with Alzheimer's disease-related dementias (ADRD) in the University of Florida Health system. They identified approximately 1,900 patients with ADRD who had taken glucosamine supplements for at least one year after their dementia diagnosis and compared them with people diagnosed with mild cognitive impairment (MCI), an early stage of memory loss that often precedes dementia.

The findings were striking: glucosamine use was associated with a 25 percent increase in mortality risk among people with ADRD. However, no increased mortality risk was found in people with MCI, suggesting the supplement may be particularly harmful once dementia has developed.

"Their study carries enough weight to further define the relationships between age of onset of glucosamine supplementation and specific types of dementia. This is especially true with respect to their findings of accelerated mortality since patients with late onset dementia can live a relatively long time, albeit in a cognitively impaired state," noted Harris A. Gelbard, MD, PhD.

Harris A. Gelbard, MD, PhD, Director of the Center for Neurotherapeutics Discovery, University of Rochester Medicine

Should People With Dementia Stop Taking Glucosamine?

Experts emphasize that while the findings are concerning, more research is needed before making definitive recommendations. The study used an aggressive mouse model of early-onset Alzheimer's disease, which represents only a small percentage of all Alzheimer's cases. Most people develop the disease later in life, and it remains unclear whether glucosamine has the same effects in this larger population.

"While these findings add to our understanding of the potential relationship between glucosamine, brain health, and Alzheimer's disease progression, the data do not establish cause and effect," stated Courtney Kloske, PhD, director of scientific engagement for the Alzheimer's Association.

Courtney Kloske, PhD, Director of Scientific Engagement, Alzheimer's Association

Kloske advised that people should not start or stop taking glucosamine without consulting their healthcare provider. However, experts do recommend that physicians discuss the potential risks with patients who have been diagnosed with dementia and are considering or currently taking glucosamine supplements.

What Are the Early Warning Signs of Dementia You Shouldn't Ignore?

While glucosamine's effects on dementia progression are concerning, early detection of cognitive decline remains one of the most important factors in slowing disease progression. Many people overlook subtle warning signs that appear before significant memory loss develops.

One of the most commonly missed early indicators involves language and spatial skills. Difficulty finding the right words, struggling to follow conversations, or needing GPS for previously familiar routes can signal early cognitive decline. These changes may appear well before noticeable memory loss.

Steps to Monitor for Dementia Symptoms

• Language Changes: Pay attention to patterns of word-finding difficulty, incorrect sentence construction, or difficulty expressing thoughts. While occasional word lapses are normal, frequent struggles warrant a conversation with your doctor.
• Spatial and Navigation Issues: Notice if you or a loved one becomes confused about familiar routes, increasingly relies on GPS for previously known directions, or has difficulty judging distances or balance.
• Behavioral and Mood Shifts: Watch for abrupt personality changes, increased anxiety, depression, or unusual behavior without an obvious explanation. Some types of dementia, such as Lewy body dementia, can cause hallucinations or delusions.
• Difficulty With Familiar Tasks: Monitor for struggles with everyday activities like managing finances, following recipes, or completing household chores that were previously routine.
• Sensory Changes: Be alert to increased noise sensitivity, changes in taste or smell, or vision problems that develop without a clear cause.

Early diagnosis can significantly improve quality of life and slow disease progression. Physicians can identify reversible causes of memory loss, such as vitamin B12 deficiency or thyroid problems, and discuss treatment options. The FDA has approved medications like Leqembi (lecanemab) that target amyloid beta plaques, the hallmark protein buildup in Alzheimer's disease, and clinical trials have shown these drugs can slow cognitive decline in people with mild to moderate disease.

Experts recommend that people over 65 consider a simple cognitive screening as part of routine healthcare, particularly if they notice any concerning changes. There is no stigma in seeking evaluation, and an early, accurate diagnosis allows doctors to develop a treatment plan tailored to each person's needs.