Understanding Brain Atrophy
Brain atrophy refers to the loss of neurons and the connections between them, resulting in a decrease in overall brain size [1.3.7]. While some degree of brain shrinkage is a natural part of aging, a process that begins around age 35 and accelerates after 60, it is significantly more pronounced in various neurological diseases [1.3.1, 1.3.7]. This loss of brain volume is a primary contributor to cognitive decline and functional impairment. For instance, in healthy individuals over 60, the annual rate of brain volume loss is about 0.5%, whereas in those with mild Alzheimer's disease (AD), this rate can double to nearly 1% [1.3.1]. Conditions most associated with accelerated brain atrophy include Alzheimer's disease, Multiple Sclerosis (MS), frontotemporal dementia, and vascular dementia [1.2.2, 1.3.1].
Medications for Alzheimer's Disease-Related Atrophy
For decades, treatments for Alzheimer's primarily managed symptoms. Cholinesterase inhibitors like donepezil (Aricept) and glutamate regulators like memantine (Namenda) can help with memory and functional decline but do not alter the underlying disease course or significantly slow atrophy [1.2.1, 1.2.3, 1.2.6]. The focus has now shifted to disease-modifying therapies that target the pathology of AD, specifically amyloid-beta plaques.
Amyloid-Targeting Monoclonal Antibodies
A new class of drugs, monoclonal antibodies, has emerged as the first to show a modest effect on slowing the progression of early-stage Alzheimer's disease [1.2.4].
- Lecanemab (Leqembi): Granted full FDA approval in July 2023, lecanemab is an intravenous therapy that selectively binds to and removes soluble amyloid-beta protofibrils, which are precursors to the amyloid plaques that disrupt brain cell communication [1.4.3, 1.4.4]. In clinical trials, lecanemab was shown to reduce amyloid plaques and moderately slow cognitive and functional decline by about 27% over 18 months compared to a placebo [1.4.7]. However, it is also associated with a greater loss in whole-brain volume compared to placebo, a phenomenon not yet fully understood, alongside risks of brain swelling and bleeding known as Amyloid-Related Imaging Abnormalities (ARIA) [1.4.6, 1.5.5].
- Donanemab (Kisunla): This medication also targets and clears amyloid-beta plaques from the brain [1.2.4]. Clinical trial results showed it slowed cognitive and functional decline by about 35% in patients with early symptomatic Alzheimer's [1.5.1, 1.5.2]. Like lecanemab, it carries risks of ARIA [1.5.1]. In July 2024, it received FDA approval for early Alzheimer's [1.2.8].
- Aducanumab (Aduhelm): Approved in 2021 under the FDA's accelerated pathway, Aduhelm also removes amyloid plaques [1.2.1]. However, its manufacturer announced the discontinuation of its production in 2024 [1.2.6].
These drugs represent a significant step forward but are only indicated for individuals in the early stages of Alzheimer's with confirmed amyloid pathology [1.2.4].
Medications for Multiple Sclerosis-Related Atrophy
In Multiple Sclerosis (MS), the immune system mistakenly attacks the central nervous system, leading to inflammation, demyelination, and subsequent brain atrophy. The rate of brain volume loss in MS patients can be 0.5% to 1.35% annually [1.6.6]. Disease-Modifying Therapies (DMTs) are the cornerstone of treatment, aiming to reduce relapse frequency and slow disease progression, which includes mitigating brain volume loss.
DMTs for MS are diverse and can be categorized by their administration route (injectable, oral, infused) and efficacy.
Comparison of MS Therapies and Brain Atrophy
| Medication Class | Examples | Effect on Brain Atrophy | Administration |
|---|---|---|---|
| S1P Receptor Modulators | Fingolimod (Gilenya), Siponimod (Mayzent), Ozanimod (Zeposia), Ponesimod (Ponvory) | Several drugs in this class, particularly ponesimod and fingolimod, have shown a significant reduction in the rate of brain volume loss compared to placebo [1.6.4, 1.6.6]. | Oral |
| Monoclonal Antibodies | Natalizumab (Tysabri), Alemtuzumab (Lemtrada), Ocrelizumab (Ocrevus) | Alemtuzumab has shown a significant effect in reducing brain volume loss [1.6.4]. Natalizumab has demonstrated potential neuroprotective effects, reducing cortical gray matter and thalamic atrophy [1.6.7]. | Infusion |
| Pyrimidine Synthesis Inhibitors | Teriflunomide (Aubagio) | Shown to significantly reduce the rate of brain volume loss compared to placebo in clinical trials [1.6.4, 1.6.5]. | Oral |
| Interferons & Glatiramer Acetate | Avonex, Rebif, Betaseron, Copaxone | These first-generation DMTs have a more modest effect on brain atrophy compared to newer, higher-efficacy therapies [1.6.2, 1.6.4]. | Injection |
Recent analyses suggest that newer oral and infused therapies like ponesimod, alemtuzumab, and teriflunomide are among the most effective at slowing the rate of brain volume loss in relapsing MS [1.6.4, 1.6.6].
The Critical Role of Lifestyle Interventions
Pharmacological treatments are only one piece of the puzzle. A robust body of evidence shows that lifestyle choices play a crucial role in preserving brain volume and cognitive function.
- Physical Exercise: Regular physical activity is one of the most effective ways to reduce brain atrophy risk. Activities like walking, gardening, swimming, or dancing are associated with larger brain volumes, equivalent to four fewer years of brain aging [1.7.1]. Exercise promotes blood flow, encourages the creation of new neurons, and may lower levels of amyloid and tau proteins [1.7.1, 1.7.2].
- Diet: A brain-healthy diet, such as the MIND or Mediterranean diet, emphasizes leafy greens, berries, nuts, whole grains, and fatty fish [1.7.2, 1.7.4]. These foods are rich in antioxidants and omega-3 fatty acids, which protect against cellular damage [1.7.2]. Recent research highlighted a 'green-Mediterranean' diet, rich in green tea and Mankai, for its ability to slow brain aging [1.7.7].
- Mental Stimulation: Engaging in cognitively challenging activities like puzzles, learning a new skill, or reading strengthens neural connections and builds cognitive reserve [1.7.2, 1.7.6].
- Quality Sleep: Sleep is when the brain clears waste products and consolidates memories. Consistent, high-quality sleep is vital for structural and functional brain health [1.7.3].
- Social Engagement: Maintaining strong social connections helps reduce stress and provides mental stimulation, both of which are protective against brain atrophy [1.7.2, 1.7.5].
Conclusion
While no single medication can completely halt or reverse brain atrophy, significant progress has been made. For early Alzheimer's disease, amyloid-targeting antibodies like lecanemab and donanemab offer a way to modestly slow cognitive decline by tackling a core pathology of the disease [1.2.3, 1.5.4]. For Multiple Sclerosis, a range of high-efficacy DMTs have proven effective at reducing the rate of brain volume loss [1.6.6]. However, these powerful medications must be balanced against their potential side effects and are most effective when combined with a proactive, brain-healthy lifestyle encompassing diet, exercise, and mental and social engagement. The future of treating brain atrophy will likely involve a personalized combination of targeted pharmacology and robust lifestyle management.
For more information on lifestyle factors, you can visit the Alzheimer's Society [1.7.5].
