Genetic Correlates of Presenile Dementia and Cognitive Decline in the Armenian Population Following COVID-19: A Case-Control Study

The presence of cognitive lapses in the post-COVID-19 period, particularly among younger individuals, suggests a potential genetic predisposition. This case-control study aimed to assess the association between neurodegeneration-associated genes and cognitive declines in the post-COVID-19 Armenian population under the age of 65. In addition, we examined other contributing factors, including depressive symptoms, hypovitaminosis D, vitamin B12 and B9 deficiencies, and some viral infections, as potential confounders or effect modifiers. A total of 162 participants (ages 19-65, Med = 43), who were exposed to SARS-CoV-2 in Armenia between 2020 and 2022, participated in this study. Standardized assessments, including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Montreal Cognitive Assessment (MoCA), were used to evaluate cognitive functions and mental status, while the Patient Health Questionnaire-9 (PHQ-9) was utilized to assess depressive symptoms. Clinical interview data, comprising yes/no self-reports regarding the presence of cognitive problems and depressive symptoms, were also included. Genetic analysis identified copy number variations (CNVs) in the <i>APP</i>, <i>PSEN1</i>, <i>PSEN2</i>, <i>MAPT</i>, and <i>GRN</i> genes, while viral infections (HSV-1, HSV-2, CMV, EBV, HIV, SARS-CoV-2, Hepatitis A, B, and C) and vitamin D, B12, and B9 deficiencies were measured. Lower cognitive performance was associated with CNVs in <i>PSEN1</i> (exons 1, 9, 12), <i>GRN</i> (exons 1, 6, 12), and <i>MAPT</i> (exons 2, 8), along with viral infections (HSV-1, HSV-2, HAV-2). The findings indicate that post-COVID-19 cognitive problems are multifactorial and are linked to genetic mutations, viral infections, age, gender, and folic acid deficiency.