Background and Purpose: Stroke is the major cause of vascular behavior and cognitive disorders worldwide. In developing countries, there is a dearth of information regarding the public health magnitude of stroke. The aim of the Fogarty-Mexico cohort was to assess the prevalence of vascular behavioral and cognitive disorders, ranging from mild vascular cognitive impairment (VCI) to vascular dementia (VaD), in a cohort of acute first-ever symptomatic stroke patients in Mexico. Methods: A total of 165 consecutive, first-ever stroke patients admitted to the National Institute of Neurology and Neurosurgery in Mexico City, were included in the cohort. Patients were eligible if they had an ischemic stroke, primary intracerebral hemorrhage, or cerebral venous thrombosis (CVT). Stroke diagnosis required the presence of an acute focal deficit lasting more than 24 h, confirmed by a corresponding lesion on CT/MRI. Stroke severity was established with the NIH Stroke Scale. The pre-stroke functional status was determined by the IQCODE. Three months after the occurrence of stroke, 110 survivor patients returned for follow-up and were able to undergo functional outcome (modified Rankin scale, Barthel index), along with neurological, psychiatric, neuropsychological, laboratory, and imaging assessments. We compared depression, demographic, and clinical and imaging features between patients with and without dementia, and between patients with VCI and those with intact cognition. Results: Of the 110 patients (62% men, mean age 56 ± 17.8, education 7.7 ± 5.2 years) 93 (84%) had ischemic strokes, 14 (13%) intracerebral hemorrhage, and 3 (3%) CVT. The main risk factors were hypertension (50%), smoking (40%), hypercholesterolemia (29%), hyperhomocysteinemia (24%), and diabetes (22%). Clinical and neuropsychological evaluations demonstrated post-stroke depression in 56%, VCI in 41%, and VaD in 12%; 17% of the latter had pre-stroke functional impairment (IQCODE >3.5). Cognitive deficits included executive function in 69%, verbal memory in 49%, language in 38%, perception in 36%, and attention in 38%. Executive dysfunction occurred in 36% of non-demented subjects, 65% of them with mild-moderate deficits in daily living activities. Female gender (p ≤ 0.054), older age (mean age 65.6 years vs. 49.3, p < 0.001), diabetes (p ≤ 0.004), illiteracy and lower education (p ≤ 0.001), and PSD (p = 0.03) were significantly higher in VCI-VaD compared with cognitively intact post-stroke subjects. We could not demonstrate an association with lesion site and distribution of the cognitive deficits. Conclusions: The Fogarty-Mexico cohort recruited relatively young acute stroke patients, compared with other Mexican stroke cohorts. PSD and VCI occurred frequently but prevalence of VaD (12%) was lower than expected. A high prevalence of treatable stroke risk factors suggests that preventive interventions are advisable.

Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children.

Objectives: To study depressive symptoms in preclinical presenilin-1 (PS1) related Alzheimer’s disease. Methods: Participants were 33 Mexican women at risk for inheriting PS1 mutations who were not demented. They were interviewed, underwent cognitive testing, and completed the Beck depression inventory (BDI). PS1 mutation status was determined. Mean BDI scores were compared between PS1 mutation carriers and non-carriers. The percentage of subjects who reported seeing a psychiatric professional, and the percentage complaining of memory loss were compared between groups. Regression analysis was used to determine whether mutation status predicted BDI scores after adjusting for age, education, mini-mental state examination, and subjective memory function. Results: PS1 mutation carriers (n = 17) scored significantly higher than non-carriers (n = 16) on the BDI (mean score, 14.4 v 6.5, p = 0.017); 24% of mutation carriers and 12.5% of non-carriers admitted having sought help from a psychiatric professional (NS). Mutation status remained a significant predictor of BDI scores after adjusting for potential covariates. Though not demented, mutation carriers tended to score lower than non-carriers on several neuropsychological tests. Conclusions: Depressive symptoms can occur early in the course of PS1 related Alzheimer’s disease, at least in women. This supports the hypothesis that depression may occur as a direct result of the neuropathology underlying Alzheimer’s disease.

Background: Prospective and case-control studies have demonstrated that memory loss and executive dysfunction occur early in Alzheimer disease (AD). Objective: To investigate these observations by the study of persons at risk for autosomal dominant forms of AD. Methods: Neuropsychological and genetic tests were performed on 51 nondemented at-risk members of 10 Mexican families with two distinct presenilin-1 (PS1) mutations. Test scores were compared between PS1 mutation carriers (MCs; n = 30) and noncarriers (NCs; n = 21) by analyses of variance, co-varying for family and specific mutation. Regression analyses were performed, taking into account age relative to the median age at dementia diagnosis in the family (adjusted age), gender, Beck Depression Inventory (BDI) scores, education, and number of APOE ε4 alleles. Subjects were divided into age tertiles and scores compared within these groups. Composite scores for Verbal Memory, Executive Function/Working Memory, Language, and Visuospatial Function were created, and these scores compared between MCs and NCs. Results: MCs performed worse than NCs on the Mini-Mental State Examination, Trails Making Tests A and B, Delayed Recall of a 10-Word List, and Wechsler Adult Intelligence Scale WAIS Block Design. In multiple linear regression analyses, BDI score, gender, and number of APOE ε4 alleles did not consistently affect test scores. The differences seen between MCs and NCs were due to differences in the oldest tertile. MCs had lower Visuospatial and Executive Function/Working Memory but not Verbal Memory or Language composite scores. Conclusions: This study is consistent with findings in sporadic Alzheimer disease of early problems with memory, visuospatial function, and particularly with executive function in PS1 mutation carriers. Depression, gender, and presence of an APOE ε4 allele did not demonstrate large influences on neuropsychological performance.

The definition of mild cognitive impairment (MCI) as a precursor for Alzheimers disease (AD) represented an important step forward in diagnosing the illness in its earliest stage. However, diagnoses based principally on cognitive performance have limitations in that there is variability between centers in which tests are employed and in how they are interpreted. Advances in our understanding of imaging and biochemical changes occurring early in the illness have improved our ability to diagnose AD in this early phase and diagnostic criteria for AD have been proposed recently based on such biomarkers. Persons inheriting autosomal dominant mutations causing familial AD (FAD) are essentially certain to develop the disease. In our studies of preclinical persons at-risk for inheriting FAD, we applied MCI diagnostic criteria to carriers of FAD mutations to ascertain the extent to which they identified persons in the earliest stages of the clinical illness. Our results indicate the relative prevalence of MCI subtypes varies considerably depending on the tests used to measure cognition. Furthermore, we found that cognitive complaints in such persons were less predictive of mutation status than were informants reports of cognitive loss. The study of FAD provides an opportunity to test various criteria for early AD and these observations should be taken into consideration in future iterations of such diagnostic criteria.

Huntington disease (HD) is an autosomal dominant genetic disorder characterized by movement disorders, cognitive impairment, and psychiatric symptoms. Relatives of HD patients experience a great burden as the latter suffer from altered social conduct and deterioration of interpersonal relationships. Theory of mind (ToM) is the ability to attribute mental states (to oneself and others). Deficits in ToM are thought to have a role in the changes in empathy and interpersonal difficulties that HD patients face. Methods: We conducted a cross sectional study to compare ToM task scores of patients with mild to moderate HD, their relatives (spouse or at-risk first-degree relative with a negative gene test) and controls.Individuals with dementia or depression were excluded. The ToM test battery included Spanish versions of the Reading Mind in the Eyes Test (RMET), Happé's Strange Stories (Social and Physical Stories subtests) and the Hinting Task. Results: The series comprised 12 HD patients, 12 relatives and 12 controls. The HD patients showed lower affective ToM scores than controls (RMET 19 [3.5] vs 23.9 [2.7], p = 0.016). Cognitive ToM tasks scores were lower in HD patients than controls as well (Happé's Social Stories 9 [2.6] vs 13 [1.9], p = 0.001; the Hinting Task 13.6 [3.4] vs 17.5 [4.0], p = 0.009). In the Hinting Task, HD relatives had lower scores in than controls (13 [3.2] vs 17.5 [4.0], p = 0.009) and similar scores to controls in the rest of the battery. Conclusion: The HD patients with mild to moderate disease severity and their relatives show ToM deficits.