Neurological soft signs and brain morphology in people living with HIV.

Neurological soft signs (NSS) are a common feature of severe psychiatric disorders such as schizophrenia but are also prevalent in organic brain diseases like HIV-associated neurocognitive disorder (HAND) or Alzheimer's disease. While distinct associations between NSS, neurocognition, and cerebral regions were demonstrated in schizophrenia, these associations still have to be elucidated in HIV. Therefore, we investigated 36 persons with HIV of whom 16 were neurocognitively healthy and 20 were diagnosed with HAND. NSS were assessed using the Heidelberg scale. NSS scores were correlated with gray matter (GM) using whole brain voxel-based morphometry. Results showed significantly elevated NSS in the HAND group when compared to the neurocognitively healthy with respect to NSS total score and the subscores "orientation" and "complex motor tasks". While the two groups showed only minor, non-significant GM differences, higher NSS scores (subscales "motor coordination", "orientation") were significantly correlated with GM reduction in the right insula and cerebellum (FWE-corrected). Our results corroborate elevated NSS in HIV+ patients with HAND in contrast to cognitively unimpaired patients. In addition, cerebral correlates of NSS with GM reductions in insula and cerebellum were revealed. Taken together, NSS in this patient group could be considered a marker of cerebral damage and neurocognitive deficits.

[Self-managed psychiatry seminars as a model of active student participation in undergraduate education]. / Seminarios autogestionados de psiquiatría como modelo de participación estudiantil activa en pregrado. Experiencia 2014-2021 en la Pontificia Universidad Católica de Chile.

In the last decade, medical students stood out as active agents in their training, which implies their involvement in the design, implementation, evaluation, and curricular co-governance. This article describes a model of active undergraduate student participation from 2014 to 2021 and compares the face-to-face and synchronous online modalities, later brought forward by the SARS-COV-2 pandemic. Annually, a call was made to UC School of Medicine undergraduate students to establish the topics and areas to be addressed during self-managed seminars. Then, medical students located in Chile were invited to attend the activity. Psychiatry was established as a priority topic in six out of eight years. Five seminars were conducted, the last two in synchronous online mode. The number of people enrolled in the online modality increased by 251% compared to the face-to-face modality (face-to-face mean = 133 ± 33 SD; online mean = 336 ± 24SD), with no significant differences in rates of attendance between modalities (Odds ratio (OR) = 1,12; 95% CI= 0,82 - 1,55; p = 0,45). The online modality was associated with a higher proportion of enrollees belonging to an institution outside the Metropolitan Region (OR 12,63; 95% CI = 8,64 - 18,46; p < 0,01). The self-managed psychiatry seminars correspond to a model of active undergraduate student participation, with the synchronous online modality representing an opportunity to massify it throughout the national territory.

[Delirium, catatonia and substance withdrawal syndrome manifested as psychomotor agitation in COVID-19: a pharmacological management approach for the general hospital setting]. / Delirium, catatonía y síndrome de abstinencia manifestados como agitación psicomotora en COVID-19: una propuesta de manejo farmacológico en el hospital general.

BACKGROUND: Neuropsychiatric symptoms can be part of the clinical spectrum of COVID-19 infections. AIM: To devise an evidence based clinical algorithm as a guide for clinicians, to identify and treat underlying clinical syndromes of psychomotor agitation, such as delirium, catatonia or substance withdrawal in patients who are hospitalized and infected with SARS-CoV-2. MATERIAL AND METHODS: A review of the literature about the pharmacological management of neuropsychiatric manifestations of COVID-19 at the general hospital, to develop a clinical protocol based on a consensus from an interdisciplinary expert panel at a Clinical Hospital. RESULTS: A consensual clinical algorithm for the management of delirium, catatonia, and substance withdrawal, manifested as psychomotor agitation in patients hospitalized with COVID-19, was developed as a clinical proposal for physicians at different levels of complexity in health services. CONCLUSIONS: Cooperation among different clinical units in the general hospital facilitated the implementation of a clinical algorithm for clinicians for the management of psychomotor agitation in COVID-19 patients.

[Negative effects of the patients' rights law and neuro-rights bill in Chile]. / Efectos negativos en la investigación y el quehacer médico en Chile de la Ley 20.584 y la Ley de Neuroderechos en discusión: la urgente necesidad de aprender de nuestros errores.

Recently, the Chilean Senate approved the main ideas of a constitutional reform and a Neuro-rights bill. This bill aims to protect people from the potential abusive use of "neuro-technologies". Unfortunately, a literal interpretation of this law can produce severe negative effects both in the development of neuroscience research and medical practice in Chile, interfering with current treatments in countless patients suffering from neuropsychiatric diseases. This fear stems from the observation of the negative effects that recent Chilean legislations have produced, which share with the Neuro-Rights Law the attempt to protect vulnerable populations from potential abuse from certain medical interventions. In fact, Law 20,584 promulgated in 2012, instead of protecting the most vulnerable patients "incapacitated to consent", produced enormous, and even possibly irreversible, damage to research in Chile in pathologies that require urgent attention, such as many neuropsychiatric diseases. This article details the effects that Law 20.584 had on research in Chile, how it relates to the Neuro-Rights Law, and the potential negative effects that the latter could have on research and medical practice, if it is not formulated correcting its errors.

Polypharmacy in a semirural community in Chile: Results from Maule Cohort.

PURPOSE: Although polypharmacy in younger populations is a growing public health concern, most studies addressing polypharmacy focus on elderly populations. Thus, polypharmacy is not yet well understood in younger populations. METHODS: Baseline data from the Maule Cohort (MAUCO) (adults aged 38-74 years) were used to study the prevalence of polypharmacy and associated participant characteristics using logistic and zero-inflated negative binomial regressions. Factors studied include age, sex, self-rated health, education, smoking, obesity, diabetes, hypertension, and other chronic conditions. RESULTS: Polypharmacy was reported by 10% of participants overall, with higher prevalence among older (≥60 years) vs middle aged (<60 years) participants (overall: 20.9% vs 6.0%, P < .0001; for those reporting any medication use: 30.2% vs 15.9%, P < .0001). Middle-aged adults reported different patterns of medication use by polypharmacy status, while older adults reported similar medication use patterns regardless of polypharmacy. Diabetes, hypertension, dyslipidemia, cardiovascular diseases, hypothyroidism, and osteomuscular diseases were significantly associated with polypharmacy. Analyses also revealed that there are MAUCO participants who are potentially being undertreated for conditions like depression. CONCLUSIONS: Research into medication use among younger and middle-aged adults and development of possible tools to deprescribe medications in this population are warranted. However, it is important that patients who need treatment receive it, and so both potential overtreatment and undertreatment need further study in this population.

Validity and Performance of the Patient Health Questionnaire (PHQ-2) for Screening of Depression in a Rural Chilean Cohort.

Validity of PHQ-2 to screen for depression was assessed in an agricultural population in Chile. The sample included 4767 adults enrolled from 2014 to 2017 in a population-based cohort of chronic disease in Maule, Chile. Receiver operating characteristic (ROC) curve analysis was used to find the optimal PHQ-2 cut-off for depression, defined as the highest Youden index, using PHQ-9 as a reference standard. Sensitivity, specificity, and Youden J index were calculated for every cut-off point of PHQ-2. Prevalence of depression measured by PHQ-9 and PHQ-2 was 18% and 18.4%, respectively. Corresponding rates for women were 24.7% and 23.6%, and 8.3% and 10.9 for men. The optimal PHQ-2 cut-off score was 3, achieved with a sensitivity of 74.6%, specificity 93.9%, and Youden index of 0.68. The area under the curve for the ROC analysis ROC curve was 0.92 (95% CI 0.91-0.93). PHQ-2 has good performance for use as a test for depression screening in a rural population of Chile and can be easily applied in areas with low resources.

The COMTp.Val158Met Polymorphism and Cognitive Performance in Adult Development, Healthy Aging and Mild Cognitive Impairment.

BACKGROUND: The impact of genetic polymorphisms on cognition is assumed to increase with age as losses of brain resources have to be compensated for. We investigate the relation of catechol-O-methyltransferase (COMT)p.Val158Met polymorphism and cognitive capacity in the course of adult development, healthy aging and the development of mild cognitive impairment (MCI) in two birth cohorts of subjects born between 1930 and 1932 or between 1950 and 1952. METHODS: Thorough neuropsychological assessment was conducted in a total of 587 participants across three examination waves between 1993 and 2008. The COMT genotype was determined as a restriction fragment length polymorphism after PCR amplification and digestion with NlaIII. RESULTS: Significant effects of the COMTp.Val158Met polymorphism were identified for attention and cognitive flexibility in the younger but not the older cohort. CONCLUSION: These results confirm the importance of the COMTp.Val158Met genotype on tasks assessing attention and cognitive flexibility in midlife but not in healthy aging and the development of MCI. Our findings suggest that the influence of COMT changes as a function of age, decreasing from midlife to aging.

Study protocol for the Maule Cohort (MAUCO) of chronic diseases, Chile 2014-2024.

BACKGROUND: Maule Cohort (MAUCO), a Chilean cohort study, seeks to analyze the natural history of chronic diseases in the agricultural county of Molina (40,000 inhabitants) in the Maule Region, Chile. Molina´s population is of particular interest because in the last few decades it changed from being undernourished to suffering excess caloric intake, and it currently has the highest national rates of cardiovascular diseases, stomach cancer and gallbladder cancer. Between 2009 and 2011 Molina´s poverty rate dropped from 24.1 % to 13.5 % (national average 20.4 %); in this period the county went from insufficient to almost complete basic sanitation. Despite these advances, chemical pollutants in the food and air are increasing. Thus, in Molina risk factors typical of both under-developed and developed countries coexist, generating a unique profile associated with inflammation, oxidative stress and chronic diseases. METHODS/DESIGN: MAUCO is the core project of the recently established Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile & Pontificia Universidad Católica de Chile. In this study, we are enrolling and following 10,000 adults aged 38 to 74 years over 10 years. All eligible Molina residents will be enrolled. Participants were identified through a household census. Consenting individuals answer an epidemiological survey exploring risk factors (psycho-social, pesticides, diet, alcohol, and physical activity), medical history and physical and cognitive conditions; provide fasting blood, urine, and saliva samples; receive an electrocardiogram, abdominal ultrasound and bio-impedance test; and take a hand-grip strength test. These subjects will be re-interviewed after 2, 5 and 7 years. Active surveillance of health events is in place throughout the regional healthcare system. The MAUCO Bio-Bank will store 30 to 50 aliquots per subject using an NIH/NCI biorepository system for secure and anonymous linkage of samples with data. DISCUSSION: MAUCO´s results will help design public health interventions tailored to agricultural populations in Latin America.

Resting state in obsessive-compulsive disorder. A review of the literature.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a chronic disease that may have a great impact on functionality. The neuroimaging study on OCD has been advancing along with the advance in the technique. Functional neuroimages suggest the participation of the prefrontal cortex and basal ganglia, forming a subcortical cortex system. Study of the resting state is a new radiological technique that makes it possible to see connectivity and activity of the neuronal zones during rest. It has been used in many psychiatric conditions, among them OCD. OBJECTIVE: To review the studies on resting state in OCD. METHOD: A systematic search was made in PubMed, Scielo and Liliacs, and 11 works for found for review. RESULTS: OCD would be caused by variations in different brain circuits. The constant perception of error and checking need could be due to an internal hyperconnection in the cingulate cortex. Difficulty to control compulsions could be caused by alterations on the prefrontal cortex level. No alterations per se of the OCD and absences in controls have been found. The differences would be more qualitative than quantitative, the OCD being a deregulation of normal processes.

Prevalence and Factors Associated with Subjective Memory Complaint in a Semi-Rural Community in Chile.

BACKGROUND: Subjective memory complaints (SMC) are commonly studied in older adults and have been identified as potentially prodromal to dementia and Alzheimer's disease. Studies among younger adults from South America are lacking. OBJECTIVE: To estimate the prevalence of SMC and the factors associated with it among Maule Cohort (MAUCO) participants. METHODS: We performed a cross-sectional analysis to estimate the prevalence of SMC and investigated its associated factors from MAUCO baseline data (N = 6,687). Within groups defined by age (38-59, 60-74) and global cognition (Mini-Mental State Examination: ≥26, 25-22, ≤21), multinomial logistic regression models evaluated risk factors for SMC (Yes, Sometimes, No). RESULTS: Overall, SMC prevalence was 16.4%; 15.9% (95% CI 14.9-16.9%) among younger and 17.6% (15.8-19.4%) among older participants. Female sex, comorbidities, and bad/fair self-reported health status (SRHS) were generally associated with higher odds of SMC. CONCLUSION: Overall prevalence of SMC was 16%. Different factors were associated with the odds of SMC depending on age and global cognitive status. Future SMC studies should include sex-specific assessments, evaluate SRHS as a moderator of SMC reporting, and the influence of the SARS-CoV-2 pandemic on SMC reporting.

Cognitive activity, education and socioeconomic status as preventive factors for mild cognitive impairment and Alzheimer's disease.

Growing epidemiological evidence suggests that premorbid participation in cognitive leisure activities (CLA) reduces the risk of dementia by increasing cognitive reserve. We investigated the differential effect of CLA, education, and socioeconomic status (SES) on the development of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants in the prospective population-based ILSE study (*1930-1932; 12-year follow-up) were examined in three examination waves (t1:1993/94; t2:1997/98; t3:2005/07). In total, 381 subjects of the original cohort (n=500) were re-examined at t3. Of these subjects 29% received the diagnosis of MCI and 7% of AD. Subjects participated in a thorough psychogeriatric examination and neuropsychological testing. Moreover, they took part in a detailed autobiographical interview and completed questionnaires including socio-demographic data and current frequency of participation in CLA. Subjects who were highly cognitively active at t1 had a significantly reduced risk of developing MCI/AD at t3 (scores adjusted for education, SES, gender, and depressive symptoms). Additionally, high education and high SES separately reduced the risk of MCI and AD. Our results confirm the hypothesis that a high level of CLA acts as a protective factor against the development of MCI and AD by increasing cognitive reserve. This effect is not accounted for by important potential confounders.

Differences in Cognitive Functioning in Two Birth Cohorts Born 20 Years Apart: Data from the Interdisciplinary Longitudinal Study of Ageing.

We compared neuropsychological functioning and prevalence of mild cognitive impairment (MCI) in two birth cohorts born 20 years apart when participants had reached the same age, i.e., the mid-60s. The study followed up 500 volunteers born 1930-1932 (C30) and 502 born 1950-1952 (C50). Participants underwent medical, neuropsychological, and psychiatric examinations in 1993-1996 (T1), 1997-2000 (T2), 2005-2008 (T3), and 2014-2016 (T4), including assessment of abstract thinking, memory performance, verbal fluency, visuo-spatial thinking, psychomotor speed, and attention. Healthy participants from C30 at T2 (n = 298) and from C50 at T4 (n = 205) were compared using multivariate ANCOVAs. Groups slightly differed with respect to age (C50: 63.86 ± 1.14 vs. C30: 66.80 ± 0.91; p < 0.05) and years of education (13.28 ± 2.89 vs. 14.56 ± 2.45). After correcting for age, C50 significantly outperformed C30 in all domains except concentration and verbal fluency. After additionally adjusting for education, C50 significantly outperformed C30 in declarative memory performances and abstract thinking only. Prevalence rates of MCI were 25.2% in C30 and 9.6% in C50 (p < 0.001). Our findings confirm the association between better educational attainment and enhanced cognitive performance in "younger" old individuals. While this association corresponds to the Flynn effect, various life course influences may have also contributed to better performance, including improvements in healthcare provision, medication, and lifestyle factors. Their overall effects may foster cognitive reserve and thus translate into the decline in MCI prevalence reported here.

Cognitive impairment with Type 2 Diabetes Mellitus among community-dwelling older adults in Chile: Prevalence, risk factors and cognitive characteristics.

Introduction: The aim of this study is to determine prevalence and risk factors of Cognitive Impairment (CI) and its association with Type 2 Diabetes Mellitus (T2DM) in subjects aged 65 years and above. Additionally, we attempt to provide a cognitive profile for T2DM group. Methodology: A cross-sectional analytical study to assess CI was carried out. We evaluated a sample of community-dwelling residents from Chile. All participants underwent a general interview, lifestyle questionnaires and a comprehensive neuropsychological battery. Regression analyses were performed to evaluate risk of CI with T2DM and influencing factors. Results between groups in the different domains of the neuropsychological assessment were compared by Student's t-tests and MANOVA. Results: Among all 358 subjects, overall T2DM prevalence were 17.3%. The prevalence of CI was higher in T2DM group compared to the healthy participants (30.7%, p < 0.001). The risk of CI was 2.8 times higher in older people with T2DM compared to older people without the diagnosis. Multiple regression analysis, adjusted for age and gender, demonstrated that age, education, presence of dyslipidemia, and T2DM duration were the predictor variables significantly associated with CI. T2DM group performed worse on global cognitive performance, attention, language, verbal memory, visual memory, visual constructional ability, and executive function. After adjusting for significant covariates from multiple regression analysis, a relationship between "cognition" and T2DM is still observed. Amnesic multi-domain impairment was the specific cognitive identified pattern for T2DM group. Conclusion: The present study confirms the high prevalence of CI with T2DM among Chilean older adults in a community-based population. T2DM is significantly associated with a higher risk of CI, and age, education, presence of dyslipidemia, and duration of T2DM are risk factors. T2DM patients with CI are impaired in multiple cognitive domains, even after adjusting covariables, resulting in an amnesic multi-domain cognitive profile.

High contextual sensitivity of metaphorical expressions and gesture blending: A video event-related potential design.

Human communication in a natural context implies the dynamic coordination of contextual clues, paralinguistic information and literal as well as figurative language use. In the present study we constructed a paradigm with four types of video clips: literal and metaphorical expressions accompanied by congruent and incongruent gesture actions. Participants were instructed to classify the gesture accompanying the expression as congruent or incongruent by pressing two different keys while electrophysiological activity was being recorded. We compared behavioral measures and event related potential (ERP) differences triggered by the gesture stroke onset. Accuracy data showed that incongruent metaphorical expressions were more difficult to classify. Reaction times were modulated by incongruent gestures, by metaphorical expressions and by a gesture-expression interaction. No behavioral differences were found between the literal and metaphorical expressions when the gesture was congruent. N400-like and LPC-like (late positive complex) components from metaphorical expressions produced greater negativity. The N400-like modulation of metaphorical expressions showed a greater difference between congruent and incongruent categories over the left anterior region, compared with the literal expressions. More importantly, the literal congruent as well as the metaphorical congruent categories did not show any difference. Accuracy, reaction times and ERPs provide convergent support for a greater contextual sensitivity of the metaphorical expressions.

[Neuropsychiatric comorbidity in HIV infection]. / Co-morbilidad neuro-psiquiátrica en infección por VIH.

BACKGROUND: The prevalence of neuropsychiatric disorders in HIV infected individuals is around 50%. Despite this, these diseases are often underdiagnosed and undertreated. Direct effects of the virus, opportunistic infections, adverse effects of antiretroviral therapy and the sociocultural context of the infected persons, contribute to the development of HIV associated neurocognitive disorder (HAND) and major depressive disorder (MDD), both of which have an impact in quality of life and disease progression. AIM: To introduce physicians in the pathophysiology, clinical features and management of psychiatric disease in seropositive patients. CONTENT: Early detection and treatment of neuropsychiatric comorbidity in HIV infected individuals improve clinical outcomes, quality of life and is an important milestone in the control of the pandemic.

Neurological soft signs (NSS) and cognitive deficits in HIV associated neurocognitive disorder.

Neurological soft signs (NSS) are frequently found in severe mental disorders, such as Alzheimer's disease, schizophrenia or HIV associated neurocognitive disorder (HAND) which includes asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia. To characterize NSS in patients with HIV we examined them with respect to neuropsychological deficits typically found in the disorder. 67 HIV + patients without a history of head trauma, opportunistic infections, severe psychiatric disorders or acute confounding comorbidities of the Central nervous system (CNS) were recruited. NSS and neuropsychological deficits were examined on the Heidelberg scale and the Cambridge Neuropsychological Test Automated Battery (CANTAB), respectively. Semantic and phonemic verbal fluency were additionally established. According to NIMH and NINDS criteria, 18 patients were diagnosed with ANI and 21 with MND, 28 showed no cognitive deficits. NSS total scores were significantly correlated with several cognitive domains and NSS subscales. These correlations were confirmed when motor performance was entered as a covariate. According to our findings, NSS in HIV positive patients are significantly correlated with deficits in a broad range of neuropsychological domains. Similar findings were reported in schizophrenia, emphasizing the transdiagnostic character of NSS and supporting NSS examination in screening HIV patients for HAND.

Type II diabetes in mild cognitive impairment and Alzheimer's disease: results from a prospective population-based study in Germany.

Diabetes mellitus type 2 (T2DM) is considered to be an important risk factor for mild cognitive impairment (MCI) and subsequent Alzheimer's disease (AD). The majority of studies relating T2DM to MCI and AD were performed in North America. We investigated the potential impact of T2DM on the development of MCI and AD in the Interdisciplinary Longitudinal Study on Adult Development and Aging which involves a representative birth cohort of subjects born between 1930 and 1932 in Germany. Subjects received a thorough psycho-geriatric examination and neuropsychological testing; particular care was taken to exclude subjects with severe medical or neurological conditions sufficient to explain the cognitive deficits, or other major psychiatric disorders. When compared to healthy subjects (n=159), patients with MCI (n=108) or AD (n=26) showed a tendency towards increased prevalence rates for T2DM (17% vs. 23%; chi2=1.7, p=0.18). In both patients with MCI and controls, T2DM was associated with psychomotor slowing but not deficits in other cognitive domains typically involved in MCI. Our findings indicate that T2DM is involved in MCI and may aggravate the clinical picture as a concomitant factor.

MRI-derived atrophy of the olfactory bulb and tract in mild cognitive impairment and Alzheimer's disease.

There is increasing histopathological evidence that the olfactory bulb and tract (OBT) is a primary focus of neurodegenerative changes in Alzheimer's disease (AD). Correspondingly, high-resolution magnetic resonance imaging revealed significant atrophy of the OBT in manifest AD. Whether these alterations are already present in mild cognitive impairment, the assumed preclinical stage of AD, has not been investigated yet. OBT volumes were assessed by manual tracing in 29 patients with mild cognitive impairment, 27 patients with probable AD, and 30 healthy controls. In a second step, voxel based morphometry was used to investigate the potential association between OBT atrophy and morphological changes in other brain regions. Patients had significantly lower OBT volumes when compared to controls, with atrophy being most prominent in the AD group. In addition, OBT atrophy was associated with a decreased medial temporal lobe (MTL) gray matter density bilaterally. Our findings indicate that neurodegeneration in OBT and MTL regions is linked and suggest that OBT volume might be a surrogate marker in AD.

[DIABDEM project: A pilot study of prevalence of cognitive impairment in diabetes mellitus in 2 Hispanic countries]. / Proyecto DIABDEM: estudio piloto de la prevalencia de deterioro cognitivo en diabetes mellitus en 2 países hispánicos.

INTRODUCTION: The prevalence of chronic noncommunicable diseases such as type 2 diabetes mellitus (T2DM) and dementia increase with ageing. In this context, an association between T2DM and cognitive impairment has been described in the literature. However, there are few studies in the Hispanic population. This research project presents a pilot study that will evaluate the feasibility of the DIABDEM project that will determine the prevalence of cognitive impairment in old people with diagnosis of T2DM in Spain and Chile. MATERIALS AND METHODS: It is a observation-based pilot study, non-experimental, descriptive-comparative and cross-sectional. The sample will involve 72 participants (39 Spaniards and 33 Chileans), 65 year-old or older, men and women, community dwelling, and who have not been previously diagnosed with dementia, with or without a T2DM diagnosis. Participants will fill in a research protocol form collecting socio-demographic and clinical data, lifestyle details, and neuropsychological variables. EXPECTED RESULTS: This study will evaluate the feasibility of the DIABDEM project that will determine the prevalence rate of cognitive impairment in old people with T2DM. On one hand, the aim of this study will establish risk and protectors factors potentially associated with the development of cognitive impairment in T2DM. On the other hand, it is expected to identify a specific neuropsychological profile in people with T2DM, proposing later a brief and useful neuropsychological battery in order to discriminate early cognitive impairment in people with T2DM. CONCLUSION: Findings in this pilot study will obtain greater knowledge about the feasibility of the DIABDEM project, which will provide evidence about cognitive complications in T2DM.

Apolipoprotein E polymorphism and brain morphology in mild cognitive impairment.

BACKGROUND: The apolipoprotein E (ApoE) genotype has been confirmed as the major genetic risk factor for late-onset Alzheimer's disease (AD). How the ApoE genotype and brain morphology relate to each other is only partly understood, particularly in mild cognitive impairment, the assumed prestage of AD. METHODS: A total of 83 subjects with mild cognitive impairment (aging-associated cognitive decline criteria) were investigated with optimized voxel-based morphometry (VBM). We tested for differences in gray and white matter densities between groups according to their ApoE status, i.e. epsilon4 allele noncarriers (n = 42), subjects with one epsilon4 allele (n = 27) and subjects with two epsilon4 alleles (n = 14). RESULTS: In individuals carrying two epsilon4 alleles, VBM revealed a decline in gray matter density predominantly in the medial temporal lobe region. Subjects with a single copy of the epsilon4 allele exhibited gray matter atrophy in the right inferior frontal gyrus. With respect to white matter changes, atrophy was only found in subjects homozygous for epsilon4 and confined to the right superior and middle temporal gyrus. CONCLUSION: Our findings support the hypothesis that the ApoE genotype in mild cognitive impairment might be associated with structural changes typically found in the early stages of AD.