Överviktskirurgi kan minska risken för demens hos patienter med typ 2- diabetes

En studie av flera stora svenska register visar att överviktskirurgi

kan kopplas till lägre risk för att utveckla demens hos patienter med övervikt och typ 2-diabetes.

 

Demenssjukdomar ökar i samhället och två viktiga riskfaktorer för demens är kraftig övervikt (obesitas) och typ 2-diabetes. Övervikt är samtidigt en bidragande orsak till typ 2-diabetes.

 

Patienter som genomgått överviktskirurgi får ofta en bestående viktnedgång. Dessutom ger en sådan operation många gånger en positiv och långvarig effekt på metabola sjukdomar som typ-2 diabetes.

 

Forskare vid Örebro Universitet, Universitetssjukhuset i Örebro och Karolinska Institutet och Danderyd sjukhus ville undersöka om överviktskirurgi kan påverka risken för demens hos patienter med obesitas och typ 2-diabetes.
– Genom att använda data från stora svenska register har vår studie försökt besvara frågan om kirurgisk behandling mot övervikt kan minska risken för att drabbas av demens hos patienter som även har typ 2-diabetes, säger Erik Stenberg, docent i kirurgi vid Örebro Universitet, överläkare vid Kirurgkliniken, Örebro Universitetssjukhus.

 

Resultatet talar för att operation mot övervikt minskar risken för att utveckla demens hos patienter med kraftig övervikt och typ 2-diabetes.
– Vi kom fram till att risken att drabbas av demens var 40 procent lägre hos de som opererats. De hade en signifikant minskad risk för Alzheimers sjukdom och vaskulär demens, säger Erik Stenberg.

 

Men forskarna kunde samtidigt se en ökad risk för alkoholrelaterad demens hos patienter med typ 2-diabetes som opererats mot sin övervikt. Det kan bero på att det finns en ökad risk för alkoholberoende efter överviktskirurgi, förklarar Erik Näslund, FoUUi-direktör och chefläkare vid Danderyds sjukhus och professor vid institutionen för kliniska vetenskaper, Danderyds sjukhus vid Karolinska Institutet.

 

– Det går bara att spekulera i orsakerna till resultaten. Viktnedgången är sannolikt en faktor. En annan faktor kan vara att samma tarmhormon (GLP-1) som används i moderna läkemedel för behandling av övervikt och diabetes, också stiger efter födointag efter överviktsoperation, säger Erik Näslund.

 

Erik Stenberg tillägger:
– Den nya klassen av läkemedel mot övervikt, så kallade GLP-1-receptoragonister, har visat sig minska risken för demens men har inte visat sig påverka sjukdomens progression hos överviktiga med redan utvecklad demens.

 

Så gjordes studien
De register som forskarna utgick från var:
• Skandinaviska obesitaskirurgiska registret (SOReg) som omfattar i princip alla patienter som opererats för obesitas sedan 2007.
• Nationella diabetesregistret (NDR) som registrerat patienter med diabetes sedan 1996.

 

Utifrån de båda registren konstruerades två matchade grupper (1 opererad patient mot 2 icke-opererade). Grupperna matchades avseende bland annat ålder, BMI, kön, diabetes, hjärtkärlsjukdom och rökning. Patienterna i den ena gruppen hade opererats för sin övervikt medan den andra inte opererats.

 

I ett andra steg samkördes grupperna med

• Socialstyrelsens register där bland annat en demensdiagnos hämtades.

 

Antalet patienter var 12 084 i den opererade gruppen och 23 581 i den icke opererade gruppen. Patienternas ålder var i medeltal drygt 48 år och de hade ett BMI om knappt 42 kg/m2. Uppföljningstiden i studien var 9 år.

 

Forskarna betonar att registerbaserade studier måste tolkas med viss försiktighet till dess att resultat från randomiserade studier finns.

 

Studien har publicerats i tidskriften Alzheimer’s and Dementia.
Stenberg E, Cao Y, Eliasson B, Näslund E. The effects of bariatric surgery on dementia in patients with diabetes and obesity. Alzheimer’s Dement. 2026;22:e71802. https://doi.org/10.1002/alz.71…

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71802

 

 

The effects of bariatric surgery on dementia in patients with diabetes and obesity
Erik Stenberg, Yang Cao, Björn Eliasson, Erik Näslund

Abstract
INTRODUCTIONType 2 diabetes (T2D) and obesity are among the most important risk factors for dementia. Although weight loss is an important preventive strategy, the impact of metabolic and bariatric surgery (MBS) on dementia risk remains contradictory.

METHODS
We conducted a propensity score matched study using nationwide, high-quality clinical registries to compare the outcomes in patients with obesity and T2D who underwent MBS with matched controls who did not undergo surgery.

RESULTS
Over a mean follow-up of 9 years, MBS was associated with a reduced risk of dementia (15-year cumulative incidence 1.8% vs. 2.7%, subdistribution hazard ratio [SHR] 0.60, 95% CI 0.47–0.76). The incidence was lower for Alzheimer’s disease (1.2% vs. 1.9%, SHR 0.56, 95% CI 0.41–0.76) and vascular dementia (0.4% vs. 0.7%, SHR 0.49, 95% CI 0.29–0.85), but increased for alcohol-related dementia (0.2% vs. 0.04%, SHR 3.67, 95%CI 1.33–10.14).

DISCUSSION
These findings suggest that the collected long-term effects of MBS may reduce the risk of developing dementia in individuals with obesity and T2D.

 

Highlights
• We examined the association between metabolic and bariatric surgery (MBS) and risk of dementia.
• Patients who underwent MBS was compared to matched individuals with type 2 diabetes (T2D) and obesity.
• The risk for dementia was reduced by 40% among patients who underwent MBS.
• Reduced risk was seen for Alzheimer’s disease (AD) and vascular dementia but increased for alcohol dementia.
• MBS may reduce the risk for new-onset dementia in patients with T2D and obesity

 

From the article

1 BACKGROUND
The global prevalence of dementia is increasing and is estimated to further increase from 57 million in 2019 to 153 million by 2050.1 While the majority of the increase is driven by demographic factors of an ageing and growing population, approximately 45% of dementia cases may be due to modifiable factors, many of which may have a direct or indirect connection with obesity.2, 3 Type 2 diabetes (T2D), obesity, and smoking have been reported as the top three modifiable contributors to dementia,4 with obesity being reported to be the most important factor among women.5 Middle-aged people with obesity have 20%–40 % higher risk of developing mild cognitive impairment and dementia later in life than those of normal weight, with increased risk with longer duration of obesity.6
Addressing modifiable risk factors remains an important strategy for preventing dementia. Metabolic and bariatric surgery (MBS) is known to result in a stable long-term weight reduction, and remission or improvement of several metabolic risk factors also linked to dementia, including hypertension, dyslipidemia, and T2D.7 However, MBS is also associated with increased risk for depression and alcohol use disorders, which in turn are known to increase the risk for dementia.3 Previous studies have suggested that MBS improves vascular efficiency and cortical thickness of the temporal lobes and may improve cognition.8, 9 Through effects on glucagon-like peptide 1 receptor agonists (GLP-1RA) and cardiovascular protective effects, MBS may be hypothesized to reduce the incidence of Alzheimer’s disease and vascular dementia.

Previous studies have reported contradictory results with both reduced risk for Alzheimer’s disease11 and an increased risk for dementia after MBS.12 The aim of the current study, therefore, was to evaluate the risk for dementia with a particular focus on Alzheimer’s disease among patients with obesity and T2D in a matched study based on high-quality data using validated, nationwide prospective databases.

 

 

RESEARCH IN CONTEXT
1. Systematic review: Studies evaluating the effects of metabolic bariatric surgery (MBS) have suggested improved cognition, but results on the risk for dementia have been contradictory.
2. Interpretation: In this propensity score matched study, patients with type 2 diabetes (T2D) and obesity that underwent MBS had a lower risk of all-cause dementia, Alzheimer’s disease and vascular dementia but an increased risk for alcohol-related dementia.
3. Future directions: The collected long-term effects of MBS may reduce the risk of developing dementia, further supporting the benefits of MBS among patients with T2D and obesity in particular for patients at increased risk for dementia.

 

 

DISCUSSION
MBS was associated with a reduced risk of Alzheimer’s disease and vascular dementia, but an increased risk of alcohol-related dementia, among patients with obesity and T2D compared with those who did not undergo MBS. The risk of Alzheimer’s disease following MBS approached that of the normal population, whereas the risk of vascular dementia remained elevated relative to the normal population.
Obesity is associated with several potential mechanisms of dementia. These include inducing inflammatory mediators that can affect the central nervous system via the blood-brain barrier, elevated cortisol, changes in microbiota, and changes in adipocyte dysfunction.6 Weight reduction and improved glycemic control are key therapeutic targets in individuals at risk for dementia since they are associated with a reduction in inflammatory markers. Although the observed effects are likely largely attributable to weight loss, non-weight-dependent mechanisms may also contribute, as has been previously described.26, 27 MBS induces changes in gut-derived hormones, including GLP-1, and has been reported to activate GLP-1/SGLT1 signaling pathways in the hippocampus, potentially reversing nerve degenerative processes.28 Pharmacological treatment with GLP-1RAs mimics aspects of these mechanisms and has been proposed to confer neuroprotective effects, with real-world studies suggesting up to a 70% reduction in dementia incidence among long-term users.29, 30

 

However, in a randomized clinical trial, oral semaglutide did not slow cognitive decline in individuals with early Alzheimer’s disease, suggesting that such therapies may be more effective for prevention than for treatment.31 Whether similar neuroprotective effects can be attributed to MBS remain uncertain and were beyond the scope of the current study. Although a substantial proportion of patients in this study received GLP-1RA therapy, the most effective agents, that is, semaglutide and tirzepatide, have only been available in Sweden since 2018 and 2024, respectively. Therefore, a meaningful subgroup analysis comparing MBS to GLP-1RA treatment was not feasible. Furthermore, real-world studies have suggested greater risk reduction for several diabetes-related complications, including cardiovascular events following MBS32, 33 compared to treatment with GLP-1RA. Therefore, the findings of the present study cannot be directly extrapolated to pharmacological treatments targeting the gut-brain axis.
MBS was associated with an increased risk of alcohol-related dementia. Alcohol overconsumption remains a challenging long-term complication of MBS, with some evidence of a higher incidence after RYGB compared with SG.34 In addition, MBS have been associated with risks of clinical depression, malnutrition, and micronutrient deficiencies.35 Social isolation, although affecting a minority of patients, may also occur postoperatively.36 Collectively, these factors may contribute to an increased risk of dementia and could explain the higher incidence of Korsakoff’s syndrome and alcohol-related dementia observed in this study. Although the absolute incidence of these conditions remained low, these findings underscore the importance of long-term follow-up and multidisciplinary support for patients undergoing MBS, with particular attention to surgical and non-surgical complications, mental health, and adherence to postoperative recommendations (including supplementation).

 

The present study was limited to patients with obesity and T2D. In parallel with the global obesity pandemic, the prevalence of T2D continues to rise, and an increasing proportion of newly diagnosed individuals living with obesity.37 People with obesity and T2D have particularly substantial benefits from MBS38 and should be considered for surgical intervention at an early stage following diagnoses, as the likelihood of remission appears to decline with longer disease duration.39 However, the exclusion of patients without T2D limits the generalizability of these findings to patients without T2D. Additionally, the study was conducted within a publicly funded Scandinavian healthcare system and a predominantly Caucasian population, which may further limit generalizability to other settings and populations. Finally, 84% of the patients in the surgical group underwent RYGB. With previous studies suggesting differences in surgical outcomes after RYGB compared to SG beyond differences in weight-related outcomes, 26 the results of the current study may therefore not necessarily be generalizable to other MBS procedures than RYGB.

 

The major strengths of this study include its nationwide design and the high inclusion rate of patients within the defined cohorts. The use of unique personal identification numbers enabled linkage to comprehensive national registries, allowing access to detailed data on specialized care, prescribed drugs, socioeconomic factors, and mortality. Nevertheless, the findings must be interpreted in light of the study’s limitations. Although the definition of dementia has been previously validated with high validity for dementia overall, the validity for specific causes of dementia (in particular unspecified dementia) remains lower.19 While the definition was strengthened by the inclusion of pharmacological treatment for Alzheimer’s disease, diagnostic delay remains a potential concern.40 Further, early personality traits associated with the development of dementia may reduce the probability of seeking surgical obesity treatment, introducing a risk for confounding by indication. To mitigate reverse causation, a 12-month washout period was applied. The Kaplan–Meier curve showed an apparent increasing risk reduction over time, further supporting the plausibility of the findings. While the propensity score match was generally well matched, imbalance remained for BMI, smoking status, and level of education in favor of the non-operated group. The variables were further adjusted for in the statistical analyses reducing the risk for a significant impact on the outcomes. Several established risk factors for dementia were accounted for in the study; others–such as prior traumatic brain injury, air pollution exposure, and physical inactivity–were not available. Including city size in the matched model may partially account for environmental exposures such as air pollution, and there is no indication of differential bias between groups with respect to these factors.
In conclusion, among patients with obesity and T2D, MBS was associated with a reduced risk of Alzheimer’s disease and vascular dementia, but an increased risk of alcohol-related dementia. Overall, MBS was associated with a lower risk of all-cause dementia in this population.

 

Läs hela artikeln free open source pdf

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71802

 

 

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