Groundbreaking new medication reduces cognitive decline due to dementia

Lewy body disease is a stealthy and relentless brain disorder that affects memory, movement, and core body functions. It includes dementia with Lewy bodies and Parkinson’s disease, with or without dementia. While often overshadowed by Alzheimer’s, it's the second most common neurodegenerative disease worldwide.

The hallmark of this illness is the buildup of abnormal protein clumps called Lewy bodies. These form in regions of the brain critical for thinking, movement, and autonomic control. As they accumulate, they wreak havoc, gradually stripping away a person’s independence and shortening life expectancy.

Dementia with Lewy bodies accounts for about 10 to 15 percent of all dementia diagnoses. In 2020, an estimated 5.5 million people lived with the condition. By 2050, that number could rise to 14 million. This looming increase signals not just a medical crisis, but a growing economic and caregiving challenge.

Compared to Alzheimer’s, dementia with Lewy bodies often leads to a quicker decline in memory and daily function. This makes life harder for patients and heavier for caregivers. The cost of managing the disease is about double that of Alzheimer’s, further highlighting the urgent need for better treatment options.

Yet, despite its toll, effective therapies remain out of reach. No disease-modifying drugs are approved globally, aside from Japan. Doctors are left to prescribe Alzheimer’s medications off-label, hoping for symptom relief. Cholinesterase inhibitors and memantine are among the most commonly used, but they don’t stop the disease from advancing.

Cholinesterase inhibitors—like donepezil, rivastigmine, and galantamine—slow the breakdown of acetylcholine, a key brain chemical tied to memory and attention. Some studies suggest these medications may help patients think more clearly and function better for a time.

A meta-analysis of ten clinical trials found rivastigmine and donepezil led to annual gains of 1 to 2.5 points on the Mini-Mental State Examination (MMSE). Memantine, on the other hand, which acts on the glutamate system in the brain, showed little or no cognitive benefit for patients with dementia with Lewy bodies.

Yet, recent comprehensive reviews reveal inconsistencies. A network meta-analysis involving eight randomized controlled trials found no significant difference in cognitive outcomes between patients treated with ChEIs or memantine and those given placebos. Furthermore, most clinical trials have short durations—typically less than a year—leaving long-term efficacy largely unexplored.

Emerging observational studies offer new hope. Research from Karolinska Institutet, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, examined 1,095 DLB patients over a decade.

The findings suggest ChEIs may not only slow cognitive decline but also improve survival. Patients treated with ChEIs showed slower cognitive deterioration over five years compared to those receiving memantine or no treatment. Additionally, ChEIs were associated with a reduced risk of death within the first year post-diagnosis.

Hong Xu, assistant professor at Karolinska Institutet and the study's first author, highlighted the critical nature of these findings. “There are currently no approved treatments for DLB, so doctors often use drugs for Alzheimer’s disease, such as cholinesterase inhibitors and memantine, for symptom relief. However, the effectiveness of these treatments remains uncertain due to inconsistent trial results and limited long-term data,” Xu said.

Maria Eriksdotter, senior author of the study, added, “Our results highlight the potential benefits of ChEIs for patients with DLB and support updating treatment guidelines.”

ChEIs’ potential benefits may extend beyond cognitive preservation. By increasing acetylcholine levels, these drugs enhance communication between neurons. More intriguingly, acetylcholine plays a role in the cholinergic anti-inflammatory pathway (CAP), a critical defense mechanism that modulates systemic inflammation. Chronic inflammation is increasingly recognized as a contributor to neurodegenerative diseases, including DLB.

Activation of CAP by ChEIs could help reduce neuroinflammation, which exacerbates neuronal damage in DLB. This anti-inflammatory effect might explain the association between ChEI use and reduced risks of severe cardiovascular events like myocardial infarction and stroke.

Furthermore, a study from the Cambridgeshire and Peterborough NHS Foundation Trust showed that ChEI users with DLB had lower all-cause mortality rates, suggesting potential systemic benefits.

While the Karolinska study presents promising data, it is important to note its observational nature. Causality cannot be firmly established, and confounding factors, such as patients’ lifestyle habits, frailty, and coexisting Alzheimer’s pathology, could influence the results. Additionally, diagnosing DLB remains challenging due to overlapping symptoms with AD and Parkinson’s disease.

Despite these limitations, the findings provide a strong case for further exploration of ChEIs in DLB management. Long-term, randomized controlled trials are necessary to confirm their benefits and elucidate their mechanisms of action. As DLB cases rise globally, advancing our understanding of effective treatments becomes increasingly urgent.

DLB’s complex pathology underscores the need for multifaceted therapeutic approaches. Current research is exploring disease-modifying therapies targeting alpha-synuclein, the main component of Lewy bodies. Immunotherapies and incretin mimetics are also under investigation, though none have shown definitive success in clinical trials so far.

In the interim, optimizing the use of ChEIs could provide critical symptom relief and improve survival for millions living with DLB. As research progresses, integrating these insights into clinical practice will be vital for enhancing patient care and quality of life.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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