GWAS for executive function and processing speed suggests involvement of the CADM2 gene.

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Syncope caused by carotid body tumor.

A 71-year-old woman with a syncope and carotid body tumor is described. On palpation of the tumor on the left side of the neck, the patient felt vertiginous and has a syncope, while ECG showed an asystolic pause of 7.6 s. The tumor was completely surgically removed. After the surgery, massage of the left side of the neck provoked neither sinus bradycardia nor asystole, and the pacing electrode was removed. Temporary pacemaker is recommended in patients with syncope caused by carotid body tumor for the safe performance of diagnostic and surgical procedures. This report describes the successful operation of carotid body tumor as a rare cause of syncope. The patient feels well one year after the surgery.

[Cardiogenic shock in acute myocardial infarct]. / Kardiogeni sok u akutnom infarktu miokarda.

Cardiogenic shock is the most important fatal complication of acute myocardial infarction (AMI). This syndrome may be considered as a severe form of left ventricular failure and the mortality rate is very high. According to the clinical classification, Killip class IV ranges from 60 to 95%, depending on authors. Shock occurs in about 15-20% of patients with AMI and accounts for at least 70% of the in-hospital deaths. During 1994, 168 patients with AMI were treated at the Intensive Care Unit of the Zagreb General Hospital, of which 14 (8.2%) developed cardiogenic shock. Ten patients experienced the first myocardial infarction, and 4 were admitted because of the second myocardial infarction, that time of anterior localization. Signs of cardiogenic shock were present in 8 (57.1%) patients already on admission. Three patients developed cardiogenic shock during the first 10 hours of hospitalization and further 3 patients during the initial 4 to 15 days of treatment. Older age prevailed. Eleven (78.5%) persons were older than 60 years of age. Eight patients demonstrated anterior infarction, 4 had inferior infarction and 2 non-Q-wave infraction. All patients had signs of left ventricular failure evidenced by pulmonary edema (Killip class IV) and later complicated by arrhythmia. Of the 14 patients who had AMI with the shock syndrome, 13 (92.8%) died; 5 (35.7%) patients during the first 2 hours, 3 (21.4%) within 24 hours of infarction, and 5 (35.7%) patients during the initial 4 to 25 days of treatment. Patients were treated conservatively, and only 3 patients received thrombolytic therapy, namely, streptokinase.