Dynamics of Cognitive Impairment in Older Adults Linked to Suicide-Related Single-Nucleotide Polymorphisms: A 3-Year Follow-Up Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Cognitive Status Assessment
2.3. DNA Extraction and Genotyping
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviation
APOE | apolipoprotein E |
IGF | insulin-like growth factor |
JCAD | Junctional Cadherin 5-Associated |
MCI | mild cognitive impairment |
MMSE | Mini-Mental State Examination |
MoCA | Montreal Cognitive Assessment |
SNPs | single-nucleotide polymorphisms |
VEGF | vascular endothelial growth factor |
References
- Jongsiriyanyong, S.; Limpawattana, P. Mild Cognitive Impairment in Clinical Practice: A Review Article. Am. J. Alzheimers Dis. Other Dement. 2018, 33, 500–507. [Google Scholar] [CrossRef] [PubMed]
- Dumas, J.A. Strategies for Preventing Cognitive Decline in Healthy Older Adults. Can. J. Psychiatry 2017, 62, 754–760. [Google Scholar] [CrossRef]
- Kirova, A.M.; Bays, R.B.; Lagalwar, S. Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer’s disease. BioMed Res. Int. 2015, 2015, 748212. [Google Scholar] [CrossRef] [PubMed]
- Anderson, N.D. State of the science on mild cognitive impairment (MCI). CNS Spectr. 2019, 24, 78–87. [Google Scholar] [CrossRef] [PubMed]
- Klimova, B.; Valis, M.; Kuca, K. Cognitive decline in normal aging and its prevention: A review on non-pharmacological lifestyle strategies. Clin. Interv. Aging 2017, 12, 903–910. [Google Scholar] [CrossRef]
- Finkel, D.; Pedersen, N.L. Processing speed and longitudinal trajectories of change for cognitive abilities: The Swedish Adoption/Twin Study of Aging. Aging Neuropsychol. Cogn. 2004, 11, 325–345. [Google Scholar] [CrossRef]
- Bellenguez, C.; Küçükali, F.; Jansen, I.E.; Kleineidam, L.; Moreno-Grau, S.; Amin, N.; Naj, A.C.; Campos-Martin, R.; Grenier-Boley, B.; Andrade, V.; et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat. Genet. 2022, 54, 412–436. [Google Scholar] [CrossRef]
- Ferrari, R.; Hernandez, D.G.; Nalls, M.A.; Rohrer, J.D.; Ramasamy, A.; Kwok, J.B.; Dobson-Stone, C.; Brooks, W.S.; Schofield, P.R.; Halliday, G.M.; et al. Frontotemporal dementia and its subtypes: A genome-wide association study. Lancet Neurol. 2014, 13, 686–699. [Google Scholar] [CrossRef]
- Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) Consortium; Fongang, B.; Sargurupremraj, M.; Jian, X.; Mishra, A.; Damotte, V.; de Rojas, I.; Skrobot, O.; Bis, J.C.; Fan, K.H.; et al. Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) consortium. A genome-wide association meta-analysis of all-cause and vascular dementia. Alzheimers Dement. 2024, 20, 5973–5995. [Google Scholar] [CrossRef]
- Sherva, R.; Zhang, R.; Sahelijo, N.; Jun, G.; Anglin, T.; Chanfreau, C.; Cho, K.; Fonda, J.R.; Gaziano, J.M.; Harrington, K.M.; et al. African ancestry GWAS of dementia in a large military cohort identifies significant risk loci. Mol. Psychiatry 2023, 28, 1293–1302. [Google Scholar] [CrossRef]
- Littlejohns, T.J.; Collister, J.A.; Liu, X.; Clifton, L.; Tapela, N.M.; Hunter, D.J. Hypertension, a dementia polygenic risk score, APOE genotype, and incident dementia. Alzheimers Dement. 2023, 19, 467–476. [Google Scholar] [CrossRef] [PubMed]
- Sun, M.; He, Q.; Sun, N.; Han, Q.; Wang, Y.; Zhao, H.; Li, G.; Ma, Z.; Feng, Z.; Li, T.; et al. Intrinsic Capacity, Polygenic Risk Score, APOE Genotype, and Risk of Dementia: A Prospective Cohort Study Based on the UK Biobank. Neurology 2024, 102, e209452. [Google Scholar] [CrossRef] [PubMed]
- Nettiksimmons, J.; Tranah, G.; Evans, D.S.; Yokoyama, J.S.; Yaffe, K. Gene-based aggregate SNP associations between candidate AD genes and cognitive decline. Age 2016, 38, 41. [Google Scholar] [CrossRef] [PubMed]
- Lin, C.H.; Lin, E.; Lane, H.Y. Genetic Biomarkers on Age-Related Cognitive Decline. Front. Psychiatry 2017, 8, 247. [Google Scholar] [CrossRef]
- Abramova, O.; Soloveva, K.; Zorkina, Y.; Gryadunov, D.; Ikonnikova, A.; Fedoseeva, E.; Emelyanova, M.; Ochneva, A.; Andriushchenko, N.; Pavlov, K.; et al. Suicide-Related Single Nucleotide Polymorphisms, rs4918918 and rs10903034: Association with Dementia in Older Adults. Genes 2022, 13, 2174. [Google Scholar] [CrossRef]
- Alothman, D.; Card, T.; Lewis, S.; Tyrrell, E.; Fogarty, A.W.; Marshall, C.R. Risk of suicide after dementia diagnosis. JAMA Neurol. 2022, 79, 1148–1154. [Google Scholar] [CrossRef]
- López, C.; Altuna, M. New Community and Sociohealth Challenges Arising from the Early Diagnosis of Mild Cognitive Impairment (MCI). J. Pers. Med. 2023, 13, 1410. [Google Scholar] [CrossRef]
- Creavin, S.T.; Wisniewski, S.; Noel-Storr, A.H.; Trevelyan, C.M.; Hampton, T.; Rayment, D.; Thom, V.M.; Nash, K.J.; Elhamoui, H.; Milligan, R.; et al. Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations. Cochrane Database Syst. Rev. 2016, CD011145. [Google Scholar] [CrossRef]
- Nasreddine, Z.S.; Phillips, N.A.; Bédirian, V.; Charbonneau, S.; Whitehead, V.; Collin, I.; Cummings, J.L.; Chertkow, H. The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 2005, 53, 695–699. [Google Scholar] [CrossRef]
- Freud, T.; Vostrikov, A.; Dwolatzky, T.; Punchik, B.; Press, Y. Validation of the Russian Version of the MoCA Test as a Cognitive Screening Instrument in Cognitively Asymptomatic Older Individuals and Those with Mild Cognitive Impairment. Front. Med. 2020, 7, 447. [Google Scholar] [CrossRef]
- Savenkova, V.I.; Zorkina, Y.A.; Ochneva, A.G.; Zeltzer, A.I.; Ryabinina, D.A.; Tsurina, A.M.; Golubeva, E.A.; Goncharova, A.S.; Alekseenko, I.V.; Kostyuk, G.P.; et al. Prevalence of anxiety and depressive disorders in a sample of Moscow residents: Comparison of the GAD-7 and HADS results with a clinical assessment. Consort. Psychiatricum. 2024, 5, CP15487. [Google Scholar] [CrossRef]
- Zucca, M.; Rubino, E.; Vacca, A.; Govone, F.; Gai, A.; De Martino, P.; Boschi, S.; Gentile, S.; Giordana, M.T.; Rainero, I. High Risk of Suicide in Behavioral Variant Frontotemporal Dementia. Am. J. Alzheimers Dis. Other Dement. 2019, 34, 265–271. [Google Scholar] [CrossRef] [PubMed]
- Rodrigues, J.F.R.; Rodrigues, L.P.; de Araújo Filho, G.M. Alzheimer’s Disease and Suicide: An Integrative Literature Review. Curr. Alzheimer Res. 2024, 20, 758–768. [Google Scholar] [CrossRef] [PubMed]
- Lozupone, M.; Donghia, R.; Sardone, R.; Mollica, A.; Berardino, G.; Lampignano, L.; Griseta, C.; Zupo, R.; Castellana, F.; Bortone, I.; et al. Apolipoprotein E genotype, inflammatory biomarkers, and non-psychiatric multimorbidity contribute to the suicidal ideation phenotype in older age. The Salus in Apulia Study. J. Affect. Disord. 2022, 319, 202–212. [Google Scholar] [CrossRef] [PubMed]
- Gujral, S.; Butters, M.A.; Dombrovski, A.Y.; Szanto, K. Late-Onset Suicide: A Dementia Prodrome? Am. J. Geriatr. Psychiatry 2021, 29, 709–713. [Google Scholar] [CrossRef]
- Zettergren, A.; Jonson, M.; Mellqvist Fässberg, M.; Najar, J.; Rydberg Sterner, T.; Seidu, N.M.; Kern, S.; Blennow, K.; Zetterberg, H.; Skoog, I.; et al. Passive and active suicidal ideation in a population-based sample of older adults: Associations with polygenic risk scores of relevance for suicidal behavior. Front. Psychiatry 2023, 14, 1101956. [Google Scholar] [CrossRef]
- Kim, J.M.; Stewart, R.; Kim, S.W.; Kang, H.J.; Kim, S.Y.; Lee, J.Y.; Bae, K.Y.; Shin, I.S.; Yoon, J.S. Interactions between a serotonin transporter gene, life events and social support on suicidal ideation in Korean elders. J. Affect. Disord. 2014, 160, 14–20. [Google Scholar] [CrossRef]
- Reyes, A.; Hermann, B.P.; Prabhakaran, D.; Ferguson, L.; Almane, D.N.; Shih, J.J.; Iragui-Madoz, V.J.; Struck, A.; Punia, V.; Jones, J.E.; et al. Validity of the MoCA as a cognitive screening tool in epilepsy: Are there implications for global care and research? Epilepsia Open 2024, 9, 1526–1537. [Google Scholar] [CrossRef]
- Faust-Socher, A.; Duff-Canning, S.; Grabovsky, A.; Armstrong, M.J.; Rothberg, B.; Eslinger, P.J.; Meaney, C.A.; Schneider, R.B.; Tang-Wai, D.F.; Fox, S.H.; et al. Responsiveness to Change of the Montreal Cognitive Assessment, Mini-Mental State Examination, and SCOPA-Cog in Non-Demented Patients with Parkinson’s Disease. Dement. Geriatr. Cogn. Disord. 2019, 47, 187–197. [Google Scholar] [CrossRef]
- Ang, L.C.; Yap, P.; Tay, S.Y.; Koay, W.I.; Liew, T.M. Examining the Validity and Utility of Montreal Cognitive Assessment Domain Scores for Early Neurocognitive Disorders. J. Am. Med. Dir. Assoc. 2023, 24, 314–320.e2. [Google Scholar] [CrossRef]
- Jia, X.; Wang, Z.; Huang, F.; Su, C.; Du, W.; Jiang, H.; Wang, H.; Wang, J.; Wang, F.; Su, W.; et al. A comparison of the Mini-Mental State Examination (MMSE) with the Montreal Cognitive Assessment (MoCA) for mild cognitive impairment screening in Chinese middle-aged and older population: A cross-sectional study. BMC Psychiatry 2021, 21, 485. [Google Scholar] [CrossRef] [PubMed]
- Aiello, E.N.; Pasotti, F.; Appollonio, I.; Bolognini, N. Trajectories of MMSE and MoCA scores across the healthy adult lifespan in the Italian population. Aging Clin. Exp. Res. 2022, 34, 2417–2420. [Google Scholar] [CrossRef] [PubMed]
- Langa, K.M.; Levine, D.A. The diagnosis and management of mild cognitive impairment: A clinical review. JAMA 2014, 312, 2551–2561. [Google Scholar] [CrossRef] [PubMed]
- Wischmann, H.A.; Logroscino, G.; Kurth, T.; Piccininni, M. Consequences of age and education correction of cognitive screening tests—A simulation study of the MoCA test in Italy. Neurol. Sci. 2024, 45, 5697–5706. [Google Scholar] [CrossRef]
- Washington, L. Dementia and the aging population: Cognitive screening within correctional health. Int. J. Prison. Health 2023, 19, 63–76. [Google Scholar] [CrossRef]
- Green, C.J.; Holly, J.M.; Bayer, A.; Fish, M.; Ebrahim, S.; Gallacher, J.; Ben-Shlomo, Y. The role of IGF-I, IGF-II, and IGFBP-3 in male cognitive aging and dementia risk: The Caerphilly Prospective Study. J. Alzheimers Dis. 2014, 41, 867–875. [Google Scholar] [CrossRef]
- Quinlan, P.; Horvath, A.; Nordlund, A.; Wallin, A.; Svensson, J. Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia. Psychoneuroendocrinology 2017, 86, 169–175. [Google Scholar] [CrossRef]
- Kimbrel, N.A.; Garrett, M.E.; Dennis, M.F.; VA Mid-Atlantic Mental Illness Research; Ashley-Koch, A.E.; Beckham, J.C. A genome-wide association study of suicide attempts and suicidal ideation in U.S. military veterans. Psychiatry Res. 2018, 269, 64–69. [Google Scholar] [CrossRef] [PubMed]
- Ciampa, C.J.; Parent, J.H.; Lapoint, M.R.; Swinnerton, K.N.; Taylor, M.M.; Tennant, V.R.; Whitman, A.J.; Jagust, W.J.; Berry, A.S. Elevated Dopamine Synthesis as a Mechanism of Cognitive Resilience in Aging. Cereb. Cortex 2022, 32, 2762–2772. [Google Scholar] [CrossRef]
- Berry, A.S.; Shah, V.D.; Baker, S.L.; Vogel, J.W.; O’Neil, J.P.; Janabi, M.; Schwimmer, H.D.; Marks, S.M.; Jagust, W.J. Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility. J. Neurosci. 2016, 36, 12559–12569. [Google Scholar] [CrossRef]
- Mullins, N.; Bigdeli, T.B.; Børglum, A.D.; Coleman, J.R.; Demontis, D.; Mehta, D.; Power, R.A.; Ripke, S.; Stahl, E.A.; Starnawska, A.; et al. GWAS of Suicide Attempt in Psychiatric Disorders and Association with Major Depression Polygenic Risk Scores. Am. J. Psychiatry 2019, 176, 651–660. [Google Scholar] [CrossRef] [PubMed]
- Akashi, M.; Higashi, T.; Masuda, S.; Komori, T.; Furuse, M. A coronary artery disease-associated gene product, JCAD/KIAA1462, is a novel component of endothelial cell-cell junctions. Biochem. Biophys. Res. Commun. 2011, 413, 224–229. [Google Scholar] [CrossRef]
- Murdock, D.G.; Bradford, Y.; Schnetz-Boutaud, N.; Mayo, P.; Allen, M.J.; D’Aoust, L.N.; Liang, X.; Mitchell, S.L.; Zuchner, S.; Small, G.W.; et al. KIAA1462, a coronary artery disease associated gene, is a candidate gene for late onset Alzheimer disease in APOE carriers. PLoS ONE 2013, 8, e82194. [Google Scholar] [CrossRef]
- Ceci, C.; Lacal, P.M.; Barbaccia, M.L.; Mercuri, N.B.; Graziani, G.; Ledonne, A. The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications. Pharmacol. Res. 2024, 201, 107101. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Zhang, Z.; Li, H.; Xia, Y.; Xing, M.; Xiao, C.; Cai, W.; Bu, L.; Li, Y.; Park, T.E.; et al. Blockage of VEGF function by bevacizumab alleviates early-stage cerebrovascular dysfunction and improves cognitive function in a mouse model of Alzheimer’s disease. Transl. Neurodegener. 2024, 13, 1. [Google Scholar] [CrossRef]
- Ryu, J.K.; Cho, T.; Choi, H.B.; Wang, Y.T.; McLarnon, J.G. Microglial VEGF receptor response is an integral chemotactic component in Alzheimer’s disease pathology. J. Neurosci. 2009, 29, 3–13. [Google Scholar] [CrossRef] [PubMed]
- Kauppi, K.; Rönnlund, M.; Nordin Adolfsson, A.; Pudas, S.; Adolfsson, R. Effects of polygenic risk for Alzheimer’s disease on rate of cognitive decline in normal aging. Transl. Psychiatry 2020, 10, 250. [Google Scholar] [CrossRef]
- Harris, S.E.; Davies, G.; Luciano, M.; Payton, A.; Fox, H.C.; Haggarty, P.; Ollier, W.; Horan, M.; Porteous, D.J.; Starr, J.M.; et al. Polygenic risk for Alzheimer’s disease is not associated with cognitive ability or cognitive aging in non-demented older people. J. Alzheimers Dis. 2014, 39, 565–574. [Google Scholar] [CrossRef]
- Andrews, S.J.; Das, D.; Cherbuin, N.; Anstey, K.J.; Easteal, S. Association of genetic risk factors with cognitive decline: The PATH through life project. Neurobiol. Aging 2016, 41, 150–158. [Google Scholar] [CrossRef]
- Lambert, J.C.; Ibrahim-Verbaas, C.A.; Harold, D.; Naj, A.C.; Sims, R.; Bellenguez, C.; Jun, G.; DeStefano, A.L.; Bis, J.C.; Beecham, G.W.; et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet. 2013, 45, 1452–1458. [Google Scholar] [CrossRef]
- Rietman, M.L.; Onland-Moret, N.C.; Nooyens, A.C.J.; Ibi, D.; van Dijk, K.W.; Samson, L.D.; Pennings, J.L.; Schipper, M.; Wong, A.; Spijkerman, A.M.; et al. The APOE locus is linked to decline in general cognitive function: 20-years follow-up in the Doetinchem Cohort Study. Transl. Psychiatry 2022, 12, 496. [Google Scholar] [CrossRef] [PubMed]
- Puri, S.; Shaheen, M.; Grover, B. Nutrition and cognitive health: A life course approach. Front. Public Health 2023, 11, 1023907. [Google Scholar] [CrossRef] [PubMed]
- Orgeta, V.; Leung, P.; Del-Pino-Casado, R.; Qazi, A.; Orrell, M.; Spector, A.E.; Methley, A.M. Psychological treatments for depression and anxiety in dementia and mild cognitive impairment. Cochrane Database Syst. Rev. 2022, 4, CD009125. [Google Scholar] [CrossRef] [PubMed]
- Gómez-Gómez, M.E.; Zapico, S.C. Frailty, Cognitive Decline, Neurodegenerative Diseases and Nutrition Interventions. Int. J. Mol. Sci. 2019, 20, 2842. [Google Scholar] [CrossRef]
- Kuchibhatla, M.; Hunter, J.C.; Plassman, B.L.; Lutz, M.W.; Casanova, R.; Saldana, S.; Hayden, K.M. The association between neighborhood socioeconomic status, cardiovascular and cerebrovascular risk factors, and cognitive decline in the Health and Retirement Study (HRS). Aging Ment. Health 2020, 24, 1479–1486. [Google Scholar] [CrossRef]
Study Inclusion | 3-Year Follow-Up | |
---|---|---|
Number of participants | 146 | 66 |
Age | 68 ± 6.3 | 71 ± 7.7 |
Women (%) | 136 (93%) | 62 (94%) |
Higher education (%) | 95 (65%) | 45 (68%) |
MMSE total score | 27 (26; 27) | 28 (27; 29) |
MoCA total score | 24 (21; 26) | 25 (22; 28) |
Moca | MMSE | Anxiety | Depression | ||
---|---|---|---|---|---|
M (Q1; Q3) | Remained | 25 (22; 26) | 27 (26; 29) | 8 (6; 10) | 7 (5; 9) |
Drop-out | 23 (20; 25) | 26 (26; 27) | 6 (4; 9) | 6 (4; 9) | |
Minimum | Remained | 11 | 22 | 0 | 1 |
Drop-out | 4 | 9 | 0 | 0 | |
Maximum | Remained | 30 | 30 | 19 | 14 |
Drop-out | 29 | 30 | 17 | 18 | |
Kruskal–Wallis χ2 | 8.24 | 10.13 | 9.79 | 3.08 | |
p | 0.004 | 0.001 | 0.002 | 0.0079 |
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Zorkina, Y.; Berdalin, A.; Morozova, I.; Andryushchenko, A.; Pavlov, K.; Pavlova, O.; Abramova, O.; Ushakova, V.; Zeltzer, A.; Kurmishev, M.; et al. Dynamics of Cognitive Impairment in Older Adults Linked to Suicide-Related Single-Nucleotide Polymorphisms: A 3-Year Follow-Up Study. Psychiatry Int. 2025, 6, 64. https://doi.org/10.3390/psychiatryint6020064
Zorkina Y, Berdalin A, Morozova I, Andryushchenko A, Pavlov K, Pavlova O, Abramova O, Ushakova V, Zeltzer A, Kurmishev M, et al. Dynamics of Cognitive Impairment in Older Adults Linked to Suicide-Related Single-Nucleotide Polymorphisms: A 3-Year Follow-Up Study. Psychiatry International. 2025; 6(2):64. https://doi.org/10.3390/psychiatryint6020064
Chicago/Turabian StyleZorkina, Yana, Alexander Berdalin, Irina Morozova, Alisa Andryushchenko, Konstantin Pavlov, Olga Pavlova, Olga Abramova, Valeriya Ushakova, Angelina Zeltzer, Marat Kurmishev, and et al. 2025. "Dynamics of Cognitive Impairment in Older Adults Linked to Suicide-Related Single-Nucleotide Polymorphisms: A 3-Year Follow-Up Study" Psychiatry International 6, no. 2: 64. https://doi.org/10.3390/psychiatryint6020064
APA StyleZorkina, Y., Berdalin, A., Morozova, I., Andryushchenko, A., Pavlov, K., Pavlova, O., Abramova, O., Ushakova, V., Zeltzer, A., Kurmishev, M., Savilov, V., Karpenko, O., Kostyuk, G., & Morozova, A. (2025). Dynamics of Cognitive Impairment in Older Adults Linked to Suicide-Related Single-Nucleotide Polymorphisms: A 3-Year Follow-Up Study. Psychiatry International, 6(2), 64. https://doi.org/10.3390/psychiatryint6020064