Alzheimer’s disease and related dementia as a component of a multiorgan senescence syndrome
Patients with Alzheimer’s disease and related dementia (ADRD) have a higher risk for comorbidities than non-cognitively impaired age-matched individuals. Because ADRD is an age-related disorder, it was hypothesized that younger patients with ADRD have a lower prevalence of comorbidities than their older counterparts. To test this hypothesis, the following four patient cohorts were defined in the TriNetX Analytics Network database based on the presence or absence of International Classification of Diseases, Tenth Revision (ICD-10) codes G30 (Alzheimer’s disease), and/or F01 (dementia in other diseases classified elsewhere) in their health care records who had health care visits from 2021 to 2023: individuals aged 65 – 80 years with and without ADRD diagnosis and individuals aged ≥90 years with and without ADRD diagnosis. Patients with ADRD in both age groups had a higher prevalence of comorbidities in almost all ICD-10 chapters than age-matched non-ADRD individuals. The younger ADRD cohort showed a comorbidity pattern that was significantly different than that of their age-matched cohort (P < 0.0001); however, it was not statistically different than the comorbidity pattern of the older ADRD cohort (P = 0.80). Similarly, the younger non-ADRD cohort showed a comorbidity pattern that was not statistically different than that of the older non-ADRD cohort (P = 0.28). These results indicated that ADRD diagnosis is associated with coincident multiorgan dysfunction in a pattern that is almost identical between the two different age groups. These data also suggested that cognitive impairment associated with ADRD is only a single component of a multiorgan senescence syndrome. Overall, this study revealed that optimizing the health care management of non-cognitive organ dysfunction in patients with ADRD may improve their overall health and, thereby, delay the progression of cognitive impairment.
- Li JQ, Tan L, Wang HF, et al. Risk factors for predicting progression from mild cognitive impairment to Alzheimer’s disease: A systematic review and meta-analysis of cohort studies. J Neurol Neurosurg Psychiatry. 2016;87(5):476-484. doi: 10.1136/jnnp-2014-310095
- Lanctôt KL, Hahn-Pedersen JH, Eichinger CS, et al. Burden of illness in people with Alzheimer’s disease: A systematic review of epidemiology, comorbidities and mortality. J Prev Alzheimers Dis. 2024;11(1):97-107. doi: 10.14283/jpad.2023.61
- Sanderson M, Wang J, Davis DR, Lane MJ, Cornman CB, Fadden MK. Co-morbidity associated with dementia. Am J Alzheimers Dis Other Demen. 2002;17(2):73-78. doi: 10.1177/153331750201700210
- Bauer K, Schwarzkopf L, Graessel E, Holle R. A claims data-based comparison of comorbidity in individuals with and without dementia. BMC Geriatr. 2014;14:10. doi: 10.1186/1471-2318-14-10
- Wang JH, Wu YJ, Tee BL, Lo RY. Medical comorbidity in Alzheimer’s disease: A nested case-control study. J Alzheimers Dis. 2018;63(2):773-781. doi: 10.3233/JAD-170786
- Doraiswamy PM, Leon J, Cummings JL, Marin D, Neumann PJ. Prevalence and impact of medical comorbidity in Alzheimer’s disease. J Gerontol A Biol Sci Med Sci. 2002;57(3):M173-M177. doi: 10.1093/gerona/57.3.m173
- Mielke MM, Dage JL, Frank RD, et al. Performance of plasma phosphorylated tau 181 and 217 in the community. Nat Med. 2022;28(7):1398-1405. doi: 10.1038/s41591-022-01822-2
- McCormick WC, Kukull WA, van Belle G, Bowen JD, Teri L, Larson EB. Symptom patterns and comorbidity in the early stages of Alzheimer’s disease. J Am Geriatr Soc. 1994;42(5):517-521. doi: 10.1111/j.1532-5415.1994.tb04974.x
- Fereshtehnejad SM, Damangir S, Cermakova P, Aarsland D, Eriksdotter M, Religa D. Comorbidity profile in dementia with Lewy bodies versus Alzheimer’s disease: A linkage study between the Swedish Dementia Registry and the Swedish National Patient Registry. Alzheimers Res Ther. 2014;6(5-8):65. doi: 10.1186/s13195-014-0065-2
- Jørgensen IF, Aguayo-Orozco A, Lademann M, Brunak S. Age-stratified longitudinal study of Alzheimer’s and vascular dementia patients. Alzheimers Dement. 2020;16:908-917. doi: 10.1002/alz.12091
- Melis RJ, Marengoni A, Rizzuto D, et al. The influence of multimorbidity on clinical progression of dementia in a population-based cohort. PLoS One. 2013;8:e84014. doi: 10.1371/journal.pone.0084014
- Haaksma ML, Vilela LR, Marengoni A, et al. Comorbidity and progression of late onset Alzheimer’s disease: A systematic review. PLoS One. 2017;12:e0177044. doi: 10.1371/journal.pone.0177044
- Hill NL, Bhargava S, Brown MJ, et al. Cognitive complaints in age-related chronic conditions: A systematic review. PLoS One. 2021;16(7):e0253795. doi: 10.1371/journal.pone.0253795
- Rajamaki B, Hartikainen S, Tolppanen AM. The effect of comorbidities on survival in persons with Alzheimer’s disease: A matched cohort study. BMC Geriatr. 2021; 21(1):173. doi: 10.1186/s12877-021-02130-z
- Peroutka SJ, Lledó-Macau A. Age demographics of Alzheimer’s disease clinical trial subjects compared to Alzheimer’s disease and related dementia patients from real world data. Neurology. 2024;102(17_Suppl_1). doi: 10.1212/WNL.0000000000205454
- Gonzales MM, Garbarino VR, Marques Zilli E, et al. Senolytic therapy to modulate the progression of Alzheimer’s disease (SToMP-AD): A pilot clinical trial. J Prev Alzheimers Dis. 2022;9(1):22-29. doi: 10.14283/jpad.2021.62
- Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer’s disease: An analysis of population-based data. Lancet Neurol. 2014;13(8):788-794. doi: 10.1016/S1474-4422(14)70136-X. Erratum in: Lancet Neurol. 2014;13(11):1070.
- Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673-2734. doi: 10.1016/S0140-6736(17)31363-6
- Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the lancet commission. Lancet. 2020;396(10248):413-446. doi: 10.1016/S0140-6736(20)30367-6
- Yaffe K, Vittinghoff E, Dublin S, et al. Effect of personalized risk-reduction strategies on cognition and dementia risk profile among older adults: The SMARRT randomized clinical trial. JAMA Intern Med. 2024;184(1):54-62. doi: 10.1001/jamainternmed.2023.6279
- Lai SW, Lin CL, Liao KF. Cataract may be a non-memory feature of Alzheimer’s disease in older people. Eur J Epidemiol. 2014;29(6):405-409. doi: 10.1007/s10654-014-9903-6
- Shang X, Zhu Z, Huang Y, et al. Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank. Br J Ophthalmol. 2023;107(2):275-282. doi: 10.1136/bjophthalmol-2021-319508
- Ma LZ, Zhang YR, Li YZ, et al. Cataract, cataract surgery, and risk of incident dementia: A prospective cohort study of 300,823 participants. Biol Psychiatry. 2023;93(9):810-819. doi: 10.1016/j.biopsych.2022.06.005
- Lee CS, Gibbons LE, Lee AY, et al. Association between cataract extraction and development of dementia. JAMA Intern Med. 2022;182(2):134-141. doi: 10.1001/jamainternmed.2021.6990
- Hokkinen K, Kaarniranta K, Jämsen E, Lampela P, Hartikainen S, Tolppanen AM. Incidence of cataract surgeries in people with and without Alzheimer’s disease. Acta Ophthalmol. 2022;100(1):68-73. doi: 10.1111/aos.14896
- Noetel M, Sanders T, Gallardo-Gómez D, et al. Effect of exercise for depression: Systematic review and network meta-analysis of randomised controlled trials. BMJ. 2024;384:e075847. doi: 10.1136/bmj-2023-075847. Erratum in: BMJ. 2024;385:q1024. doi: 10.1136/bmj.q1024
- Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: The evidence. CMAJ. 2006;174(6):801-809. doi: 10.1503/cmaj.051351
- Kruk J. Physical activity in the prevention of the most frequent chronic diseases: An analysis of the recent evidence. Asian Pac J Cancer Prev. 2007;8:325-338.
- Bishop-Bailey D. Mechanisms governing the health and performance benefits of exercise. Br J Pharmacol. 2013;170(6):1153-1166. doi: 10.1111/bph.12399
- Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): A randomised controlled trial. Lancet. 2015;385(9984):2255-2263. doi: 10.1016/S0140-6736(15)60461-5
- Isaacson RS, Hristov H, Saif N, et al. Individualized clinical management of patients at risk for Alzheimer’s dementia. Alzheimers Dement. 2019;15(12):1588-1602. doi: 10.1016/j.jalz.2019.08.198