Mild cognitive impairment (MCI) is an intermediate state between normal cognition and early dementia and is not considered as a typical outcome of brain aging. It has been estimated that 10% to 20% of individuals above 65 years of age will be diagnosed as having MCI. The increased rate of dementia and the importance of early detection of its forerunners have encouraged researchers to focus on detecting MCI and modifiable risk factors with the hope of developing better ways of managing dementia and its consequences. The main aim of this study was to systematically review the related literature concerning the cognitive changes in the spectrum of cognitive aging to cognitive impairment. Articles included in this review were identified through searching the databases of PubMed, Psych Info, Embase, ProQuest, and Scopus. Many domains like verbal memory, language, executive function, visual memory, attentional skills, and working memory showed acceptable predictive power. Testing subdomains such as executive function, speed of processing, working memory and semantic language are critical and others may indicate some suggestions for further clinical deteriorations in normal individuals. Although various cognitive instruments have been used for evaluation of impaired cognitive domains, it remains challenging to select the most appropriate ones having high‐level accuracy and their related cognitive subdomains. It also revealed that none of the identified cognitive domains solely fulfilled the criteria for MCI screening; in clinical settings, multiple neuropsychological batteries may be used for one single cognitive domain, while longitudinal studies prefer the use of at least two cognitive measures for each domain to improve accuracy and research settings might focus on only a single neuropsychological test. However, along with episodic memory, testing for amnestic MCI, executive function could increase the chance of early detection of MCI. Executive control has been found to deteriorate the earliest in MCI patients.

Background: Approximately 2% of the human core promoter short tandem repeats (STRs) reach lengths of ≥6 repeats, which may in part be a result of adaptive evolutionary processes and natural selection. A single-exon transcript of the human nescient helix loop helix 2 (NHLH2) gene is flanked by the longest CA-repeat detected in a human protein-coding gene core promoter (Ensembl transcript ID: ENST00000369506.1). NHLH2 is involved in several biological and pathological pathways, such as motivated exercise, obesity, and diabetes. Methods: The allele and genotype distribution of the NHLH2 CA-repeat were investigated by sequencing in 655 Iranian subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 290) and matched controls (n = 365). The evolutionary trend of the CA-repeat was also studied across vertebrates. Results: The allele range was between 9 and 25 repeats in the NCD cases, and 12 and 24 repeats in the controls. At the frequency of 0.56, the 21-repeat allele was the predominant allele in the controls. While the 21-repeat was also the predominant allele in the NCD patients, we detected significant decline of the frequency (p < 0.0001) and homozygosity (p < 0.006) of this allele in this group. Furthermore, 12 genotypes were detected across 16 patients (5.5% of the entire NCD sample) and not in the controls (disease-only genotypes; p < 0.0003), consisting of at least one extreme allele. The extreme alleles were at 9, 12, 13, 18, and 19 repeats (extreme short end), and 23, 24, and 25 repeats (extreme long end), and their frequencies ranged between 0.001 and 0.04. The frequency of the 21-repeat allele significantly dropped to 0.09 in the disease-only genotype compartment (p <

The human X-linked zinc finger MYM-type protein 3 (ZMYM3) contains the longest GA-STR identified across protein-coding gene 5′ UTR sequences, at 32-repeats. This exceptionally long GA-STR is located at a complex string of GA-STRs with a human-specific formula across the complex as follows: (GA)8-(GA)4-(GA)6-(GA)32 (ZMYM3-207 ENST00000373998.5). ZMYM3 was previously reported among the top three genes involved in the progression of late-onset Alzheimer’s disease. Here we sequenced the ZMYM3 GA-STR complex in 750 human male subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 268) and matched controls (n = 482). We detected strict monomorphism of the GA-STR complex, except of the exceptionally long STR, which was architecturally skewed in respect of allele distribution between the NCD cases and controls [F (1, 50) = 12.283; p = 0.001]. Moreover, extreme alleles of this STR at 17, 20, 42, and 43 repeats were detected in seven NCD patients and not in the control group (Mid-P exact = 0.0003). A number of these alleles overlapped with alleles previously found in schizophrenia and bipolar disorder patients. In conclusion, we propose selective advantage for the exceptional length of the ZMYM3 GA-STR in human, and its link to a spectrum of diseases in which major cognition impairment is a predominant phenotype.

Background Older adults may be more prone to death anxiety than their younger counterparts. This study explores factors affecting death anxiety based on gender differences. Methods In this correlational study, 450 older adults referred to the health centres in the city of Bukan, Iran were recruited by using a randomised sampling method. Next, data were collected about the demographic questionnaire, anxiety about ageing, death anxiety, mental well‐being, perceived social support, and quality of life questionnaire. The Spearman correlation coefficient was used to determine the correlation between variables, and the predictors of death anxiety were evaluated using quintile regression. Relationship between death anxiety and other variables was evaluated by the Structural Equation Model (SEM). The study was approved by the Tabriz University of Medical Sciences Ethics Committee (Ethics Code: IR.TBZMED.REC.1397.304). Results The results showed that death anxiety in men had a significant relationship with the level of literacy (P = 0.047), body self‐imaging (P = 0.031), and perceived social activity (P = 0.033). Among women, death anxiety had a significant relationship with physical activity (P = 0.007) and perceived social activity (P = 0.002). Additionally, quintile regression analysis was calculated: among men, anxiety about ageing was related to death anxiety (β = 0.182, P = 0.05), while in women, only perceived social support was associated to death anxiety (β = −0.376, P = 0.05). Finally, according to SEM, a significantly different level of predictability of mental well‐being was found for death anxiety among older men and women. Conclusion Understanding the gender differences about death anxiety by the healthcare system might be useful in controlling and reducing a variety of concerns among elders who experience high levels of anxiety of death.

BackgroundWhile there is an ongoing trend to identify single nucleotide substitutions (SNSs) that are linked to inter/intra-species differences and disease phenotypes, short tandem repeats (STRs)/microsatellites may be of equal (if not more) importance in the above processes. Genes that contain STRs in their promoters have higher expression divergence compared to genes with fixed or no STRs in the gene promoters. In line with the above, recent reports indicate a role of repetitive sequences in the rise of young transcription start sites (TSSs) in human evolution.ResultsFollowing a comparative genomics study of all human protein-coding genes annotated in the GeneCards database, here we provide a genome-scale portrait of human-specific short- and medium-size (≥ 3-repeats) tri- and tetranucleotide STRs and STR motifs in the critical core promoter region between − 120 and + 1 to the TSS and evidence of skewing of this compartment in reference to the STRs that are not human-specific (Levene’s test p < 0.001). Twenty-five percent and 26% enrichment of human-specific transcripts was detected in the tri and tetra human-specific compartments (mid-p < 0.00002 and mid-p < 0.002, respectively).ConclusionOur findings provide the first evidence of genome-scale skewing of STRs at a specific region of the human genome and a link between a number of these STRs and TSS selection/transcript specificity. The STRs and genes listed here may have a role in the evolution and development of characteristics and phenotypes that are unique to the human species.