This week Dr Ray O’Connor takes a look at the potential role of medication and vaccination on the prevention of dementia and cognitive decline
Vaccination and Dementia Risk
The aim of this systematic review1 was to evaluate the association between influenza vaccination and dementia risk in the overall population and the high-risk populations for dementia, such as patients with chronic kidney disease (CKD), chronic obstruction pulmonary disease (COPD) and vascular disease. The authors searched PubMed, Embase and CENTRAL from inception to April 6, 2025.
Dr Ray O’Connor
Eight cohort studies were included with 9,938,696 subjects. Except for one study, the risk of bias of all other included studies was deemed to be low. Influenza vaccination was associated with a reduced risk of incident dementia in high-risk populations for dementia, but not in the overall population (HR 0.93; 95% CI: 0.86-1.01). For high-risk populations, more than one dose of influenza vaccination showed an association with a lower risk of incident dementia (2-3 doses: HR 0.84; 95% CI: 0.76-0.92; ≥ 4 doses: HR 0.43; 95% CI: 0.38-0.48). The authors concluded that influenza vaccination was associated with a decreasing risk of incident dementia in a dose-response manner.
Another systematic review2 looked at whether adults receiving commonly administered adult vaccines had a lower risk of developing mild cognitive impairment (MCI) and dementia. The authors searched PubMed, Embase and Web of Science from inception to January 1, 2025. They looked at observational studies comparing dementia and MCI incidence between vaccinated and unvaccinated adults aged ≥50 years.
Twenty-one studies (n=104,031,186 participants) were included. Vaccination against herpes zoster was associated with a reduced risk of any dementia (RR 0.76) and Alzheimer’s disease (RR0.53) Influenza vaccination was linked to a reduction in dementia risk (RR0.87), as was pneumococcal vaccination (RR0.64) for Alzheimer’s disease. Tetanus, diphtheria, pertussis (Tdap) vaccination was also associated with a significant reduction for any dementia (RR 0.67).
The authors concluded that adult vaccinations, particularly against herpes zoster, influenza, pneumococcus and Tdap, are associated with a lower risk of dementia. They recommend that vaccination strategies should be incorporated into public health initiatives for dementia prevention.
Glucose lowering agents and dementia risk in people with diabetes
Diabetes is a risk factor for dementia, but it is not known whether specific diabetes medications ameliorate this risk. The objective of this systematic review and meta-analysis3 was to evaluate such medication’s effect on the risk of developing dementia, MCI, or cognitive decline. The authors searched three databases until November 21, 2023. They included randomized controlled trials (RCT), cohort, and case-control studies assessing association between antidiabetic medication and future dementia, MCI, or cognitive decline.
They meta-analysed studies separately for individual drug classes and their comparators (no medication, placebo, or another drug). Forty-two studies fulfilled inclusion criteria. The findings were that Glucagon-like peptide-1 receptor agonists (GLP-1 RA) versus placebo reduced dementia risk by 53% in three RCTs (n=15,820, RR=0.47) and 27% in three case-control studies (n=312,856, RR=0.73]. Repaglinide was superior to glibenclamide by 0.8 points on the Mini-Mental State Examination scale in another RCT. Meta-analysis of seven longitudinal studies showed glitazones (n=1,081,519, RR=0.78) were associated with reduced dementia risk. Metformin (n=999,349, RR=0.94), sulfonylureas (RR=0.98), dipeptidyl peptidase-IV inhibitors (DPP-1V) (n=192,802, RR=0.86) and insulin (n=571,274, RR=1.09) were not.
Most studies were observational and limited by confounding by indication. The authors concluded that in people with diabetes, RCTs consistently showed GLP-RAs reduce future dementia risk. Glitazones consistently showed protective effects, without heterogeneity, suggesting potential generalizability of these results. Metformin, sulfonylureas, insulin, and DPP-1V studies had inconsistent findings.
Another independent study on the same topic4 also found benefit in GLP-1RAs. The authors searched PubMed and Embase databases for studies published from inception of the database to July 11, 2024 on people with diabetes. The studies selected were randomized clinical trials comparing cardioprotective glucose-lowering therapy with controls that reported dementia or change in cognitive scores.
Cardioprotective glucose-lowering therapies were defined as drug classes recommended by guidelines for reduction of cardiovascular events, based on evidence from phase III randomized clinical trials.
The primary outcome measure was dementia or cognitive impairment. The secondary outcomes were primary dementia subtypes, including vascular and Alzheimer dementia and change in cognitive scores. Twenty-six randomized clinical trials were eligible for inclusion (n=164,531 participants), of which 23 trials (n=160,191 participants) reported the incidence of dementia or cognitive impairment, including 12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were identified).
The mean (SD) age of trial participants was 64.4 (3.5) years and 57 470 (34.9%) were women. Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR], 0.83 [95%CI, 0.60-1.14]). Among drug classes, GLP-1RAs were associated with a statistically significant reduction in dementia (OR, 0.55 [95%CI, 0.35-0.86]), but not SGLT2is (OR, 1.20].
The authors concluded that in people with diabetes, while cardioprotective glucose-lowering therapies were not associated with an overall reduction in all-cause dementia, this meta-analysis of randomized clinical trials found that glucose lowering with GLP-1RAs was associated with a statistically significant reduction in all-cause dementia.
Systemic Drugs and Cognitive Impairment
Previous meta-analyses have found that systemic medications may modulate dementia risk. The aim of this umbrella review of meta analyses5 was to provide an overview of this evidence to guide clinical practice and future research.
The authors searched databases from inception to April 15, 2024. Only peer-reviewed meta-analyses examining dementia risk and systemic medications in humans were included. Sixty-eight meta-analyses were included, across 11 drug categories. Across meta-analyses, available data were primarily observational. Confounding by indication and potential reverse causality were important limitations.
Randomised-controlled data were rare but supported an association between treatment of hypertension and reduced dementia incidence. Overall, the authors found moderate certainty evidence of reduced risk of dementia associated with anti-hypertensives, statins, sodium-glucose transport protein 2 (SGLT2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and moderate certainty of increased risk with anticholinergics. The authors concluded that currently there is insufficient evidence to advise repurposing any systemic drugs with the primary aim of reducing dementia risk.
They recommend proactive treatment of hypertension to reduce risk of all-cause dementia. Their findings did not find a difference between antihypertensive drug classes, but dementia risk was associated with blood pressure reading. In addition, they advised avoidance of anticholinergic drugs in cognitive impairment, with assessment of anticholinergic burden and consideration of alternatives during routine clinical contacts.
References:
Yang W-K et al. Influenza vaccination and risk of dementia: a systematic review and meta-analysis. Age Ageing 2025 Jul 1;54(7): afaf169. DOI: 10.1093/ageing/afaf169.
Maggi S et al. Association between vaccinations and risk of dementia: a systematic review and meta-analysis. Age and Ageing 2025; 54: afaf331 https://doi.org/10.1093/ageing/afaf331.
Hui EK et al. Effect of diabetes medications on the risk of developing dementia, mild cognitive impairment, or cognitive decline: A systematic review and meta-analysis. Journal of Alzheimer’s Disease 2025, Vol. 104(3) 627–648 DOI: 10.1177/13872877251319054.
Seminer A et al. Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis. JAMA Neurol. 2025;82(5):450-460. DOI:10.1001/jamaneurol.2025.0360 Published online April 7, 2025.
Belessiotis-Richards C et al. Systemic medications and dementia risk: a systematic umbrella review. Molecular Psychiatry (2025) 30:5578–5599; https://doi.org/10.1038/s41380-025-03129-3