In this review, researchers argue that abnormal glucose metabolism is closely tied to Alzheimer’s disease (AD) pathogenesis and may help explain why some diabetes therapies are being studied for cognitive benefit. The article describes how impaired brain glucose use, disrupted insulin signaling, blood-brain barrier dysfunction, mitochondrial injury, oxidative stress, inflammation, and TXNIP-related pathways may all contribute to amyloid-beta accumulation, tau phosphorylation, and neurodegeneration. In that framework, AD is presented not just as a disorder of plaques and tangles, but also as one linked to broader metabolic dysfunction, especially insulin resistance and impaired cellular energy handling in the brain.

The review then examines whether antidiabetic drugs and certain herbal compounds might help treat AD by targeting those metabolic pathways. It highlights promising preclinical and some early clinical signals for agents such as GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors, insulin, and metformin, though the evidence is mixed and in some cases contradictory, especially for metformin. It also surveys herbal candidates such as curcumin, resveratrol, berberine, geniposide, ginsenosides, and quercetin, noting potential anti-inflammatory, antioxidant, and insulin-signaling effects. Researchers emphasize that most of this evidence remains preclinical and that bioavailability, inconsistency, and lack of robust human trials remain major limitations. Overall, the authors suggest targeting glucose metabolism may open new avenues for AD treatment, but they stop well short of claiming that any of these approaches are proven therapies yet.

Reference: Wang Y, Hu H, Liu X, Guo X. Hypoglycemic medicines in the treatment of Alzheimer's disease: Pathophysiological links between AD and glucose metabolism. Front Pharmacol. 2023 Feb 23;14:1138499. doi: 10.3389/fphar.2023.1138499. PMID: 36909158; PMCID: PMC9995522.

Lewy body dementia is a complex neurodegenerative disorder that affects far more than cognition alone, with symptoms spanning cognitive, neuropsychiatric, motor, autonomic, gastrointestinal, urinary, and sleep domains. In this review, experts combined available evidence with Delphi-based clinical consensus to outline a practical management approach for these overlapping problems. For cognitive symptoms, donepezil and rivastigmine have the strongest evidence and are generally considered first-line. Memantine may offer some benefit but has shown mixed results. Neuropsychiatric symptoms such as hallucinations, delusions, anxiety, depression, and apathy often require careful assessment with caregiver input, and nonpharmacologic strategies are preferred first when possible. Antipsychotics must be used with great caution because patients with Lewy body dementia can have severe sensitivity reactions, and even helpful treatments in one domain may worsen symptoms in another.

The review emphasizes that management should be multidisciplinary and highly individualized because patients commonly experience parkinsonism, falls, orthostatic hypotension, constipation, urinary problems, REM sleep behavior disorder, insomnia, daytime sleepiness, and other disabling symptoms that can interact with one another. Evidence for many treatments remains limited, so clinicians often must rely on Parkinson’s disease data, expert consensus, and careful monitoring of tradeoffs. Nonpharmacologic measures such as physiotherapy, environmental modification, sleep hygiene, swallowing precautions, and caregiver education remain essential. Medications like levodopa, midodrine, fludrocortisone, melatonin, or selected bowel and bladder therapies may help specific symptoms in selected patients. Overall, the authors conclude that Lewy body dementia care requires coordinated, multispecialty support and that major evidence gaps remain, especially the need for larger, high-quality clinical trials focused on this population.

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Reference: Taylor JP, McKeith IG, Burn DJ, et al. New evidence on the management of Lewy body dementia. Lancet Neurol. 2020 Feb;19(2):157-169. doi: 10.1016/S1474-4422(19)30153-X. Epub 2019 Sep 10. PMID: 31519472; PMCID: PMC7017451.

This randomized controlled trial tested whether an intensive, multimodal lifestyle program could help people already diagnosed with mild cognitive impairment or early dementia due to Alzheimer’s disease. Over 20 weeks, participants in the intervention group followed a highly structured program that included a whole-food, minimally processed plant-based diet, regular exercise, stress management, support groups, and selected supplements, while the control group continued usual care. Compared with controls, the intervention group showed statistically significant advantages on several standard measures of cognition and function, including the CGIC, CDR-SB, and CDR-Global. It showed borderline significance on the ADAS-Cog in the primary analysis. Results were even stronger in a sensitivity analysis. The study also found that the control group worsened across all four measures, while the intervention group generally improved or declined less.

The findings also were supported by favorable shifts in several biomarkers, including the plasma Aβ42/40 ratio, insulin, LDL cholesterol, GlycA, and ketones, as well as beneficial microbiome changes. In addition, dose-response relationships showed that greater adherence to the lifestyle program was associated with greater cognitive benefit. The authors conclude that comprehensive lifestyle change may help slow, stop, or even improve early Alzheimer’s-related cognitive decline, though they stress that the intervention was intensive and that substantial adherence appeared necessary.  

Reference: Ornish D, Madison C, Kivipelto M, et al. Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer's disease: a randomized, controlled clinical trial. Alzheimers Res Ther. 2024 Jun 7;16(1):122. doi: 10.1186/s13195-024-01482-z. PMID: 38849944; PMCID: PMC11157928.