Publication|Articles|June 19, 2026
- Vol 43, Issue 6
Evidence-Based Nonpharmacological Interventions in Schizophrenia: Focus on Cognitive Impairment
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Key Takeaways
- Cognitive deficits affect >80% of people with schizophrenia, involving attention, processing speed, memory, executive function, and social cognition, with early onset and heterogeneous but often stable trajectories.
- Functional impairment is strongly cognition-driven, worsening vocational outcomes, interpersonal functioning, and participation in meaningful activities, and cognitive status also predicts premature mortality.
Learn how cognitive remediation, aerobic exercise, and reducing secondary risks can boost thinking skills and daily functioning in schizophrenia.
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Schizophrenia is a severe mental disorder that frequently features reduced functional capacity, leading to impairment in real-world outcomes and high levels of disability.1,2 Individuals living with schizophrenia often also have to face high levels of internalized stigma, with reduced life engagement and diminished quality of life.3,4 Moreover, schizophrenia also carries a significantly increased mortality risk compared with the general population, leading to an estimated average of 15 years of life lost. Although this is partially due to an increase in suicide risk, noncommunicable diseases, including cardiovascular issues, diabetes, obesity, and cancer, represent the primary sources of increased mortality.5
Cognitive impairment represents one of the core features of schizophrenia6 and has been theorized as such since the earliest conceptualizations of the disorder, dating back more than a century, with the definition of the disorder as “dementia praecox.”7 In fact, a cognitive performance that is at least 1 standard deviation below that of the general population can be found in more than 80% of diagnosed individuals,8 with impairments that can be observed both in neurocognitive domains (eg, attention, processing speed, memory, and executive functions)9 and in social cognition domains (eg, emotion processing, theory of mind).10 These deficits can be observed from an early age, often predating the full onset of psychotic symptoms, and although their longitudinal trajectory can be quite heterogeneous, most individuals feature a stable level of impairment.
However, the relevance of cognitive impairment in schizophrenia is not only theoretical and scientific but also eminently clinical. In fact, cognitive impairment represents one of the main determinants of functional impairment in schizophrenia, and is therefore directly responsible for negative outcomes in several real-world contexts of utmost relevance for individuals living with the disorder. This includes difficulties in developing and maintaining personal relationships—whether amical or romantic—finding and maintaining remunerated employment, and engaging in and enjoying personal and recreational activities.11
Recent studies have also highlighted that, among other factors, cognitive impairment represents a predictor of premature mortality in individuals living with schizophrenia.12 Considering all of these issues, cognitive impairment has increasingly become a treatment target of relevance, both from the perspective of clinicians and of mental health service users.13
Secondary Cognitive Impairment in Schizophrenia
It has also been recently theorized that cognitive impairment in individuals with schizophrenia might be subdivided into 2 distinct components: (1) primary cognitive impairment, which is related to the core neurobiological alterations that characterize the disorder; and (2) secondary cognitive impairment, which is the result of exposure to factors that have a negative impact on cognitive performance and by which individuals living with schizophrenia are disproportionately affected in terms of frequency and intensity.14
These include pharmacological elements such as elevated anticholinergic burden, antipsychotic polypharmacy, and prolonged use of benzodiazepines.15-17
Substance abuse, including cannabis, cocaine, alcohol, and even tobacco smoking, negatively affects cognitive performance in individuals with schizophrenia.18-21 Metabolic conditions such as metabolic syndrome, dyslipidemia, obesity, and diabetes also appear to have a role in determining worse cognitive outcomes. Finally, social isolation, autistic symptoms, and depressive symptoms have all been linked to cognitive impairment in people with schizophrenia.22-25
Although the concept of secondary cognitive impairment in schizophrenia is still largely theoretical, addressing the sources of secondary cognitive impairment and removing them with dedicated treatment where possible could produce substantial benefits to the global cognitive health of service users.24
Treatment of Cognitive Impairment in Schizophrenia
Antipsychotic medications, which represent the cornerstone of the pharmacological treatment of schizophrenia,26 do not provide substantial benefits for cognitive impairment. Several meta-analytical studies have shown that all antipsychotic medications provide only minimal benefits for cognitive performance, and even these benefits become unsubstantial when corrected for improvement of psychotic symptoms.27 Various pharmacological agents designed specifically to improve cognitive performance have been investigated, and several more are currently under scrutiny, but, to date, no molecule has provided significant evidence of effectiveness.28
Despite the lack of pharmacological solutions, cognitive impairment in schizophrenia can and should be treated. This is where evidence-based psychosocial interventions come into play.29
Cognitive remediation (CR) is a behavioral training intervention that specifically targets cognitive impairment, aiming to provide long-term functional benefits. Several recent meta-analytic investigations have provided consistent evidence of its effectiveness in improving both cognitive and real-world outcomes.30 The presence of an active and trained therapist, the repetition of cognitive exercises, and the development of novel cognitive strategies and their integration in the real-world context of participants represent its core constituent elements.30 It presents a good acceptability profile,31 and the effects have been shown to be durable over time.32
Considering this wealth of evidence, CR represents a treatment for cognitive impairment in schizophrenia recommended with the highest level of endorsement in the European Psychiatric Association guidance document.33
Aerobic physical exercise is another intervention with a solid evidence base attesting to its effectiveness. In fact, besides providing substantial benefits on metabolic and health-related outcomes in individuals with schizophrenia, it has also been shown to improve core dimensions of the disorder, such as positive and negative symptoms.34,35 A meta-analytic investigation has recently found that at least 90 minutes per week for a duration of 12 weeks is also capable of providing measurable and clinically significant improvement in cognitive performance, whereas another meta-analysis has shown real-world functional improvements can also be observed.36,37 Moreover, CR and aerobic exercise–based programs can be combined in structured rehabilitation programs to provide even faster and more impactful improvements.38
Noninvasive brain stimulation, including transcranial magnetic stimulation and transcranial direct current stimulation, is a promising approach to treat both negative symptoms and cognitive impairment, with recent evidence attesting positive effects particularly in the working memory domain.39 Aerobic exercise can also be effectively combined with CR40; however, the relatively small number of available individual studies and the significant heterogeneity of results still hinder the recommendation of such approaches as fully evidence-based treatments.
Concluding Thoughts
In conclusion, cognitive impairment represents a core element of schizophrenia, with a staggering negative impact on service users’ lives. Although pharmacological treatment options are lacking, evidence-based behavioral interventions can provide substantial improvements. CR represents the most effective treatment for cognitive impairment in schizophrenia, and aerobic exercise can also provide substantial benefits. Noninvasive brain stimulation appears promising, but more scientific evidence is still needed. Finally, considering sources of secondary cognitive impairment and directly addressing them may provide substantial benefits to the overall cognitive health of individuals living with schizophrenia.
Prof Vita is a professor of psychiatry at the University of Brescia, chair of the psychiatric clinic, and director of the Department of Mental Health of Spedali Civili Hospital, Brescia.
Dr Nibbio is a postdoctoral fellow in the Department of Clinical and Experimental Sciences at the University of Brescia.
Prof Barlati is an associate professor of psychiatry in the Department of Clinical and Experimental Sciences at the University of Brescia.
References
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5. Solmi M, Croatto G, Fornaro M, et al.
6. Javitt DC.
7. Kraepelin E, Barclay RM, Robertson GM, eds. Dementia Praecox and Paraphrenia. E&S Livingstone;1919:13-24.
8. McCleery A, Nuechterlein KH.
9. Reichenberg A.
10. Barlati S, Minelli A, Ceraso A, et al.
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13. Nibbio G, Baglioni A, Bertoni L, et al.
14. Vita A, Nibbio G, Barlati S.
15. Mancini V, Latreche C, Fanshawe JB, et al.
16. Lähteenvuo M, Tiihonen J.
17. Liu C, Zhang L, Pan Q, et al.
18. Bourque J, Potvin, S.
19. Frazer KM, Richards Q, Keith DR.
20. Hetland J, Hagen E, Lundervold AJ, Erga AH.
21. Lisoni J, Nibbio G, Ardesi M, et al.
22. Salvi V, Tripodi B, Cerveri G, et al.
23. Duan Y, Jiang S, Yin Z, et al.
24. Komatsu H, Onoguchi G, Sato Y, et al.
25. Chen XJ, Wang DM, Zhou HX, et al.
26. McCutcheon RA, Pillinger T, Varvari I, et al.
27. Feber L, Peter NL, Chiocchia V, et al.
28. Vita A, Nibbio G, Barlati S.
29. Barlati S, Nibbio G, Vita A.
30. Vita A, Barlati S, Ceraso A, et al.
31. Vita A, Barlati S, Ceraso A, et al.
32. Vita A, Barlati S, Ceraso A, et al.
33. Vita A, Gaebel W, Mucci A, et al.
34. Galderisi S, De Hert M, Del Prato S, et al.
35. Fernández-Abascal B, Suárez-Pinilla P, Cobo-Corrales C, et al.
36. Shimada T, Ito S, Makabe A, et al.
37. Korman N, Stanton R, Vecchio A, et al.
38. Deste G, Barlati S, Nibbio G, et al.
39. García-Fernández L, Muñoz-Gualan AP, Romero-Ferreiro V, et al.
40. Lisoni J, Nibbio G, Baglioni A, et al.
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