Neuropsychological Assessment for Early Detection and Diagnosis of Dementia: Current Knowledge and New Insights.

Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of neuropsychological assessment in the characterization of cognitive changes associated with dementia syndrome at different states. The first section describes the early indicators of cognitive decline and the major barriers to their identification. Further, the optimal cognitive screening conditions and the most widely accepted tests are described. The second section analyzes the main differences in cognitive performance between Alzheimer's disease and other subtypes of dementia. Finally, the current challenges of neuropsychological assessment in aging/dementia and future approaches are discussed. Essentially, we find that current research is beginning to uncover early cognitive changes that precede dementia, while continuing to improve and refine the differential diagnosis of neurodegenerative disorders that cause dementia. However, neuropsychology faces several barriers, including the cultural diversity of the populations, a limited implementation in public health systems, and the adaptation to technological advances. Nowadays, neuropsychological assessment plays a fundamental role in characterizing cognitive decline in the different stages of dementia, but more efforts are needed to develop harmonized procedures that facilitate its use in different clinical contexts and research protocols.

A novel abbreviated version of the Luria neuropsychological diagnosis battery: reliability and convergent validity in Spanish older adults.

OBJECTIVE: To estimate the test-retest and inter-rater reliability of the new Spanish abbreviated version of the Luria Neuropsychological Diagnosis (DNA-2) battery for older adults. METHOD: A total of thirty cognitively healthy volunteers were examined in this study. The participants completed a comprehensive standardized assessment, encompassing cognitive and functional performance. Intraclass correlation coefficients (ICC) were used to examine test-retest and inter-rater reliability. One month was allowed between administrations. Furthermore, correlations between Luria DNA-2 (total and domain subscores) and other classical cognitive measures were explored. RESULTS: The test-retest reliability on the overall Luria DNA-2 score was high (ICC= .834, 95% CI [.680, .917], p < .001). Furthermore, the inter-rater reliability for the total score demonstrated an excellent concordance between administrators (ICC= .990, 95% CI [.979, .995], p < .001). Positive and significant correlations were observed between Luria DNA-2 (both total and domain subscores) and the Addenbrooke's Cognitive Examination (ACE-III; ρ = .857, p < .001). CONCLUSIONS: This study supports the adequate reliability of the Luria DNA-2, as an abbreviated neuropsychological battery, for assessing cognitive performance in Spaniards aged 55 years and older. Future studies should continue to explore the psychometric properties of the Luria DNA-2, particularly those related to its diagnostic validity for early detection of cognitive impairment.

Is cognitive reserve associated with the prevention of cognitive decline after stroke? A Systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analyses of the effect of socio-behavioral cognitive reserve (CR) proxies on cognitive decline after stroke. METHOD: Three journal search and indexing databases (PubMed, Scopus and Web of Sciences) were crossed to examine the scientific evidence systematically. In addition, meta-analytic techniques, using mixed-effect methods, were carried out to estimate the impact (pooled effect size) of CR proxies on either dementia incidence or cognitive decline after stroke. RESULTS: Twenty-two studies were included in the systematic revision, whereas nineteen of them were eligible for the meta-analysis. The findings showed that high education is associated with a decreased rate of post-stroke dementia. Moreover, other CR proxies (e.g., occupation, bilingualism or social interaction) demonstrate a protective effect against non-dementia cognitive decline after stroke, although some inconsistencies were found in the literature. Regarding the meta-analysis, occupational attainment and education) showed a protective effect against post-stroke cognitive impairment diagnosis in comparison with a mixed category of different CR proxies. Second, a main cognitive change effect was found, pointing to greater cognitive change after stroke in those with low vs. high CR. CONCLUSIONS: Our findings emphasize that CR may prevent cognitive decline after stroke, but this effect can be modulated by different factors such the CR proxy and individual characteristics such as age or type of lesion. The methodological divergences of the studies (i.e., follow-up intervals, cognitive outcomes) need unification to diminish external sources of variability for predicting rates of cognitive decline after stroke.

Education and Literacy as Risk Factors of Dementia after Stroke and Transient Ischemic Attack: NEDICES Study.

BACKGROUND: A protective effect of education on cognitive decline after stroke has been claimed, but evidence from prospective population-based cohorts is very limited. The differential role of literacy and education on dementia after stroke remains unexplored. OBJECTIVE: This research addresses the role of education and literacy in dementia incidence after stroke and transient ischemic attack (TIA). METHODS: 131 participants with stroke or TIA were identified within the population-based NEDICES study (N = 5,278 persons). Participants were fully assessed at baseline (1994-1995) and incident dementia diagnosis was made by expert neurologists (DSM-IV criteria) after a mean follow-up of 3.4 years. Adjusted Cox regression analyses were applied to test the association between education, literacy, and dementia risk. RESULTS: Within the 131 subjects with stroke or TIA, 19 (14%) developed dementia at follow-up. The Cox's regression model (age and sex adjusted) showed that low education (HR = 3.48, 95% CI = 1.28, 9.42, p = 0.014) and literacy (HR = 3.16, 95% CI = 1.08, 9.22, p = 0.035) were significantly associated with a higher dementia risk. Low education was also associated with dementia when main confounders (i.e., cognitive/functional performance) were considered in the Cox's model. However, after including stroke recurrence, only low/null literacy (versus education) remained as significant predictor of dementia. Finally, low/null literacy showed an effect over-and-above education on dementia risk when both factors were introduced in the adjusted Cox's regression. CONCLUSION: These findings underline the importance of literacy to estimate cognitive decline after stroke in low-educated populations.

The Distinctive Role of Grounded Optimism and Resilience for predicting Burnout and Work Engagement: A study in Professional Caregivers of Older Adults.

BACKGROUND: Resilience and optimism have been proposed as psychological resources which may help to cope better with work demands, preventing negative consequences of stress, whereas external locus of control (ELC) is considered an intra-psychic vulnerability factor associated with increased burnout. Noteworthy, the specific role of these overlapping constructs on the prevention of burnout and promotion of work engagement, respectively, remains unclear. OBJECTIVE: The main aim of this study was to compare the differential significance of resilience and optimism, joined with ELC, on the prediction of burnout and work engagement. METHOD: A sample of 265 professional caregivers of dependent older adults was assessed using an extensive standardized protocol. Optimism and ELC were measured using the Palenzuela's Battery of Generalised Expectancies of Control, and the Connor-Davidson Scale was used to estimate resilience. Moreover, the Maslach Burnout Inventory and the Utrecht Work Engagement Scale were used to measure burnout and work engagement, respectively. Different hierarchical regression models were conducted with burnout and work engagement as dependent factors. RESULTS: The results showed that more than half (51%) variance in resilience was accounted by grounded optimism scores. The ELC was the main explanatory factor of burnout, whereas optimism and resilience were the best predictors of work engagement. Finally, even after controlling the effect of resilience, the effect of optimism remained significant for predicting work engagement. CONCLUSIONS: These findings support distinctive role resilience and optimism, two closely related psychological constructs, for promoting work engagement and reducing burnout in professional caregivers of older adults.

The health status: the ignored risk factor in dementia incidence. NEDICES cohort.

BACKGROUND: The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF. AIM: To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis. METHODS: We analysed different objective health measures and SPH as RF for dementia and AD incidence in 4569 participants of the NEDICES cohort by means of Cox-regression models. The mean follow-up period was 3.2 (range: 0.03-6.6) years. RESULTS: Ageing, low education, history of stroke, and "poor" SPH were the main RF for dementia and AD incidence, whereas physical activity was protective. "Poor" SPH had a hazard ratio = 1.66 (95% CI 1.17-2.46; p = 0.012) after controlling for different confounders. DISCUSSION: According to data from NEDICES cohort, SPH is a better predictor of dementia and AD than other more objective health status proxies. SPH should be considered a holistic and biologically rooted indicator of health status, which can predict future development of dementia and AD in older adults. CONCLUSIONS: Our data indicate that it is worthwhile to include the SPH status as a RF in the studies of dementia and AD incidence and to explore the effect of its improvement in the evolution of this incidence.

Cognitive reserve and brain maintenance in aging and dementia: An integrative review.

This research is an integrative review of scientific evidence differentiating between cognitive reserve (CR) and brain maintenance concepts. Thus, we have examined how CR socio-behavioral proxies (i.e. education, occupational attainment, and leisure activities) may help to cope with age-related cognitive decline and negative consequences of brain pathology. We also analyze lifestyle factors associated with brain maintenance or the relative absence of change in neural resources over time. Medline and Web of Science databases were used for the bibliographic search in the last 20 years. Observational cohort studies were selected to analyze the effect of different CR proxies on cognitive decline, including dementia incidence, whereas studies employing functional neuroimaging (fMRI) were used to display the existence of compensation mechanisms. Besides, structural MRI studies were used to test the association between lifestyle factors and neural changes. Our findings suggest that education, leisure activities, and occupational activity are protective factors against cognitive decline and dementia. Moreover, functional neuroimaging studies have verified the existence of brain networks that may underlie CR. Therefore, CR may be expressed either through a more efficient utilization (neural reserve) of brain networks or the recruitment of additional brain regions (compensation). Finally, lifestyle factors such as abstaining from smoking, lower alcohol consumption, and physical activity contributed to brain maintenance and were associated with the preservation of cognitive function. Advances in multimodal neuroimaging studies, preferably longitudinal design, will allow a better understanding of the neural mechanisms associated with the prevention of cognitive decline and preservation of neural resources in aging.

Psychosocial Factors Associated with Burnout and Self-Perceived Health in Spanish Occupational Therapists.

(1) Background: There are few studies of burnout syndrome (BS) in occupational therapists (OTs), and protective factors for BS have received little attention in the scientific literature. This research aimed to estimate the prevalence of BS, characterize the associated psychosocial factors, and analyze their relationship with health in a sample of Spanish OTs. (2) Methods: A total of 127 therapists completed the Maslach Burnout Inventory (MBI) and other standardized questionnaires measuring: personality traits (reduced five-factor personality inventory, NEO-FFI), coping styles (Coping Strategies Questionnaire, CAE), work-family conflict (Survey Work-Home Interaction Nijmegen, SWING), professional factors (role ambiguity/clarity and modified role conflict questionnaires), and the perception of health (Goldberg's General Health Questionnaire). Several correlational and multiple regression analyses were performed to study the psychosocial predictors of burnout and its relationship with health perceptions. (3) Results: 15.8% of the professionals presented BS, with emotional exhaustion (EE; 38.7%) being the most compromised dimension. Neuroticism, role conflict, negative work-family interaction, and open emotional expression (OE) significantly predicted a higher EE. The main predictors of cynicism (CY) were being male, role conflict, and OE. Role conflict, role ambiguity and social support-seeking were significant predictors of reduced professional efficiency (PE). (4) Conclusions: A high percentage of OTs with BS suggests the need for increased awareness of the importance of this syndrome in the health community. It would be critical to consider the protective factors (i.e., emotional management, social support) that help promote OTs' well-being and health.

Physical activity and risk of Parkinson's disease and parkinsonism in a prospective population-based study (NEDICES).

To investigate whether physical activity (PA) is a protective factor for the incidence of Parkinson's disease (PD) and parkinsonism after three years of follow-up. All participants of this study were obtained from the Neurological Disorders in Central Spain (NEDICES), a prospective population-based cohort survey of older subjects (≥65 years) that comprised 5278 census-based participants at baseline (1994-1995). A modified version of Rosow-Breslau questionnaire was applied to categorize PA into active versus sedentary group. The final diagnosis of PD and parkinsonism was made by an expert neurologist. Cox regression models (CRM) adjusted for several covariates (sex, age, education, alcohol consumption, tobacco, stroke, hypertension and body mass index) were used to calculate the association between PA (active group vs. sedentary) and risk of PD and parkinsonism after three years. 22 incident PD and 25 incident parkinsonism cases were identified among 2943 participants with available PA information (57.1% female; mean age = 73.28 ± 6.24 years) after three years of follow-up. The CRM showed that the active group (vs. sedentary) showed a lower risk of parkinsonism (Hazard ratio (HR) = 0.18; 95% CI [0.07-0.51]; p = 0.0001). However, this effect was restricted to men (HR = 0.34; 95% CI [0.11-0.99], p < 0.05) for incident PD. PA may be a protective factor for incident parkinsonism, whereas this effect was only significant for men in the case of PD. The mechanisms implicated for brain maintenance in active individuals and the neurophysiological differences behind the role of sex on PD are discussed.

Accelerated forgetting in temporal lobe epilepsy: When does it occur?

OBJECTIVE: The main goal of the study was to analyse differences in the forgetting rates of Temporal Lobe Epilepsy (TLE) patients at different intervals (30 sec, 10 min, 1 day and 1 week) compared with those of healthy controls. A secondary aim of this research was to provide an assessment of the relationship between clinical epilepsy-related variables and forgetting rates in TLE patients. METHOD: The sample was composed of 14 TLE patients and 14 healthy matched controls. All participants underwent a full standardised neuropsychological assessment including general intelligence, executive functioning, memory, language and other variables, such as depression, anxiety or everyday memory failures. Two specific memory tasks, consisting of cued recall of 4 short stories and 4 routes, were carried out at four different intervals. RESULTS: There was a significant difference between groups at 10-min interval on the stories task, with the TLE group displaying greater forgetting than healthy controls. None of the other intervals on either task showed significant group differences. No differences were found when controlling for clinical epilepsy-related variables. CONCLUSION: Forgetting of verbal information at 10 min was greater in patients with TLE compared with controls, but accelerated longer term forgetting was not found. This study suggests that a late consolidation process is not necessarily impaired in TLE patients.

The role of education in executive functions, behavioral problems and functional performance in people with schizophrenia.

OBJECTIVE: This cross-sectional study examined the influence of education on executive functions, behavioral problems and functional performance in people with chronic schizophrenia. METHOD: Our sample was composed of 116 subjects with a schizophrenia diagnosis (evolution time = 17.5 ± 9.5 years) from consecutive referrals to the Rehabilitation Unit of Benito Menni Hospital (Valladolid, Spain). All participants completed an extensive standardized protocol including a neuropsychological testing of executive functions (processing speed, working memory, inhibition, interference control, mental flexibility), the assessment of behavioral symptoms, and functional performance. Hierarchical regression models (HRMs) were carried out to determine whether education (in years) relates to executive functions after controlling for the effect of demographics, IQ, and clinical factors. RESULTS: Both IQ and years of education were associated with a later onset of the illness. Specifically, high education (in years) significantly correlated with fewer behavioral problems and better functional performance in daily life. Further, HRMs showed that education was associated with digit span and sematic verbal fluency tasks after controlling for the effect of age, sex, and IQ as covariates. CONCLUSIONS: Higher education may ameliorate executive deficits in patients with chronic schizophrenia and, in turn, diminish the behavioral and functional problems of the illness. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Predementia constructs: Mild cognitive impairment or mild neurocognitive disorder? A narrative review.

BACKGROUND: Predementia is a heuristic umbrella concept to classify older adults with cognitive impairment who do not suffer dementia. Many diagnostic entities have been proposed to address this concept, but most of them have not had widespread acceptance. AIMS: To review clinical definitions, epidemiologic data (prevalence, incidence) and rate of conversion to dementia of the main predementia constructs, with special interest in the two most frequently used: mild cognitive impairment (MCI) and minor neurocognitive disorder (miNCD). METHODS: We have selected in three databases (MEDLINE, Web of Science and Google scholar) the references from inception to 31 December 2019 of relevant reviews, population and community-based surveys, and clinical series with >500 participants and >3 years follow-up as the best source of evidence. MAIN RESULTS: The history of predementia constructs shows that MCI is the most referred entity. It is widely recognized as a clinical syndrome harbinger of dementia of several etiologies, mainly MCI due to Alzheimer's disease. The operational definition of MCI has shortcomings: vagueness of its requirement of "preserved independence in functional abilities" and others. The recent miNCD construct presents analogous difficulties. Current data indicate that it is a stricter predementia condition, with lower prevalence than MCI, less sensitivity to cognitive decline and, possibly, higher conversion rate to dementia. CONCLUSIONS: MCI is a widely employed research and clinical entity. Preliminary data indicate that the clinical use of miNCD instead of MCI requires more scientific evidence. Both approaches have common limitations that need to be addressed.

Clinical Utility of Two- and Three-Dimensional Visuoconstructional Tasks in Mild Cognitive Impairment and Early Alzheimer's Disease.

OBJECTIVE: The aim of this study was to investigate whether different types of visuoconstructional abilities are useful to distinguish individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from healthy controls (HCs). METHOD: We selected 20 patients with MCI and 14 with AD diagnosis based on standard criteria. The neuropsychological performance of MCI and AD groups were compared with that of a group of 11 HCs using a standard neuropsychological battery and visuoconstructional tasks that differed difficulty and type of implicated skills (graphomotor vs. non-graphomotor): two-dimensional (Clock Drawing Test, CDT; Block Design, BD; and Visual Puzzles, VP) and three-dimensional Block Construction (TBC). RESULTS: AD group scored significantly lower than HCs in BD, VP and TBC tasks, but no significant differences were found between HCs and MCI. CDT (copy condition) scores did not differ significantly among the groups. The receiver operating characteristic analysis showed that BD [sensitivity (se) = .85, specificity (sp) = .90, Youden index (J) = .76], VP (se = .78 and sp = .72, J = .51) and TBC (se = .71, sp = 100, J = .71) were accurate tasks to discriminate between AD and HCs. Moreover, BD tasks (se = .85, sp = .70, J = .55) and TBC (se = .71, sp = .80, J = .51) showed fair accuracy to differentiate between MCI and AD groups. CONCLUSIONS: These findings indicate that non-graphomotor visuoconstructional tasks are already impaired in the early stages of AD, but are preserved in MCI individuals when compared with HCs.

Mediating effect of social support on the relationship between resilience and burden in caregivers of people with dementia.

OBJECTIVE: This study examined different predictive factors of burden in a sample of family caregivers of patients with dementia (PWD). In particular, the influence of social support and resilience on burden was tested, considering potential mediation effects. METHODS: A total of 283 primary and family caregivers in Spain were evaluated using a standardized protocol to assess sociodemographic characteristics, clinical state of PWD and specific variables of caregiving and care providers. RESULTS: The role of caregiver of PWD was more common in women, reporting significantly higher levels of burden than men. Resilience and social support accounted for most of the variance in burden. Furthermore, social support partially mediated the relationship between resilience and burden in caregivers. CONCLUSIONS: Caregivers' resilience and social support are protective factors against burden in caregivers of PWD. Both factors should be considered for tailored interventions aimed at reducing the health costs of burden in this population.

Influence of cognitive reserve in schizophrenia: A systematic review.

OBJECTIVE: To perform a systematic review of the influence of sociobehavioural indicators of cognitive reserve (CR) in the risk of schizophrenia, the clinical manifestations of the disease, and cognitive intervention programs (CRT) carried out with these patients. METHOD: A cross search was made by two independent reviewers in Pubmed and PsycINFO databases using keywords "schizophrenia" and "cognitive reserve." Twenty-one studies which analyzed different CR proxies were selected and the level of evidence was classified according to the Oxford Centre for Evidence-Based Medicine. RESULT: People with higher CR may have a lower risk of developing schizophrenia and a later onset of disease. In addition, they present better neuropsychological and functional performance in the illness course. However, the suspected influence of CR on the effectiveness of CRT in patients with schizophrenia is currently unresolved. CONCLUSION: Our findings suggest that higher CR delays the clinical diagnosis threshold and severity of the symptoms in patients with schizophrenia. However, effect of singular sociobehavioral measures on clinical expression and benefits of intervention program need further investigation.

Characterizing functional alterations in instrumental activities of daily living using latent class analysis: a population-based study (NEDICES).

Background and Objectives: The existence of different patterns of functional impairment in older adults has scarcely been addressed. This research investigates major patterns of functional impairment based on Pfeffer's Functional Activity Questionnaire (FAQ).Research Design and Methods: The participants come from NEDICES (Neurological Disorders in Central Spain), a prospective population-based cohort study. A total of 3837 individuals without dementia who completed the Spanish version of the FAQ was selected. Latent Class Analysis (LCA) was carried out to examine potential cluster subgroups based on FAQ responses.Results: The FAQ showed good internal consistency (Cronbach's alpha: 0.86) and moderate correlation (r = -.40) with cognitive performance on the Mini-Mental State Examination (MMSE-37). The response patterns revealed the presence of three latent classes: absence of functional alteration (Class 1), established functional alteration (Class 2), and minimal functional alteration (Class 3). Moreover, the probability of resolving Items 2 ('shopping alone for…'), 3 ('heating water…'), 4 ('preparing a balanced meal'), and 9 ('travelling out of neighbourhood…') was close to 0% for Class 2 membership, while those with the lowest probability of resolution for Class 3 were Items 2 and 9. Items 3 and 4 were the best to discriminate between different grades of functional alterations (Class 2 vs. Class 3).Discussion and Implications: Our findings indicate that the combination of overall FAQ score and item response pattern may help to classify individuals with different subtypes of functional impairment. The Spanish version of the FAQ is a useful tool for detection of functional impairment in older adults.

Reliable change indices for the 37-item version of the MMSE in Spanish older adults.

OBJECTIVE: The aim of this study was to establish reliable change and regression-based change score norms on the 37-item version of MMSE in older Spanish adults at the three-year follow-up. METHOD: All subjects of this research were selected from the Neurological Disorders in Central Spain (NEDICES), a prospective population-based cohort study of older adults (65 years and over). Of the 4208 individuals free from neurological disorders in this cohort, 2073 participants completed the MMSE-37 at baseline and at the three-year follow-up. Reliable Change Indices were computed for the 80, 90% and 95 confidence intervals (CIs). Multiple regression analyses were used to derive equations for predicting MMSE-37 post-test scores taking into account baseline scores, time to follow-up and sociodemographic factors. RESULTS: The MMSE-37 obtained a marginal test-retest reliability (.70). The results showed significant effects of education, age, and sex on the MMSE-37 change scores. After correcting for regression to the mean, at least a 6-point change on MMSE-37 (three-years follow-up) is required to be classified as reliable (90% CI). CONCLUSIONS: These findings demonstrate that the MMSE-37 is a reliable test-retest measure whose change scores are significantly influenced by sociodemographic factors. Importantly, small changes on this measure require a cautious interpretation.

Non-steroidal anti-inflammatory drugs use in older adults decreases risk of Alzheimer's disease mortality.

Alzheimer disease (AD) mortality risk in a large cohort of subjects treated or not with non-steroidal anti-inflammatory drugs (NSAIDs) is unknown. Our objective was to determine whether NSAIDs use is associated with decreased risk of AD mortality. In this prospective, population-based study (Neurological Disorders in Central Spain [NEDICES]) of 5,072 people without AD (aged 65 years and older), sociodemographic, comorbidity factors, and current medications were recorded at baseline. Community-dwelling older adults were followed for a median of 12.7 years, after which the death certificates of deceased participants were examined. 2,672 (52.7%) of 5,072 participants died, including 504 (18.9%) NSAIDs users and 2,168 (81.1%) non-users. Of the 2,672 deceased participants, 113 (4.2%) had AD as a cause of death (8 [1.6%] among NSAIDs users and 105 [4.8%] among non-users, chi-square = 10.70, p = 0.001). In an unadjusted Cox model, risk of AD mortality was decreased in NSAIDs users (hazard ratio [HR] for AD mortality = 0.35, 95% confidence interval [CI] 0.17-0.72, p = 0.004) when compared to non-users. After adjusting for numerous demographic factors and co-morbidities, the HR for AD mortality in NSAIDs users was 0.29, 95% CI 0.12-0.73, p = 0.009. Stratified analyses showed a significantly decreased risk of AD mortality with aspirin, whereas non-aspirin NSAIDs only showed a statistical trend toward significance in the adjusted Cox regression models. NSAIDs use was associated with 71% decreased risk of AD mortality in older adults. Our results support the hypothesis that NSAIDs use is a protective factor of developing AD.

The role of stress in drug addiction. An integrative review.

BACKGROUND: The high prevalence and burden to society of drug abuse and addiction is undisputed. However, its conceptualisation as a brain disease is controversial, and available interventions insufficient. Research on the role of stress in drug addiction may bridge positions and develop more effective interventions. AIM: The aim of this paper is to integrate the most influential literature to date on the role of stress in drug addiction. METHODS: A literature search was conducted of the core collections of Web of Science and Semantic Scholar on the topic of stress and addiction from a neurobiological perspective in humans. The most frequently cited articles and related references published in the last decade were finally redrafted into a narrative review based on 130 full-text articles. RESULTS AND DISCUSSION: First, a brief overview of the neurobiology of stress and drug addiction is provided. Then, the role of stress in drug addiction is described. Stress is conceptualised as a major source of allostatic load, which result in progressive long-term changes in the brain, leading to a drug-prone state characterized by craving and increased risk of relapse. The effects of stress on drug addiction are mainly mediated by the action of corticotropin-releasing factor and other stress hormones, which weaken the hippocampus and prefrontal cortex and strengthen the amygdala, leading to a negative emotional state, craving and lack of executive control, increasing the risk of relapse. Both, drugs and stress result in an allostatic overload responsible for neuroadaptations involved in most of the key features of addiction: reward anticipation/craving, negative affect, and impaired executive functions, involved in three stages of addiction and relapse. CONCLUSION: This review elucidates the crucial role of stress in drug addiction and highlights the need to incorporate the social context where brain-behaviour relationships unfold into the current model of addition.