Associations of CAIDE Dementia Risk Score with MRI, PIB-PET measures, and cognition

Ruth Stephen, Yawu Liu, Tiia Ngandu, Juha O Rinne, Nina Kemppainen, Riitta Parkkola, Tiina Laatikainen, Teemu Paajanen, Tuomo Hänninen, Timo Strandberg, Riitta Antikainen, Jaakko Tuomilehto, Sirkka Keinänen Kiukaanniemi, Ritva Vanninen, Seppo Helisalmi, Esko Levälahti, Miia Kivipelto, Hilkka Soininen, Alina Solomon, Ruth Stephen, Yawu Liu, Tiia Ngandu, Juha O Rinne, Nina Kemppainen, Riitta Parkkola, Tiina Laatikainen, Teemu Paajanen, Tuomo Hänninen, Timo Strandberg, Riitta Antikainen, Jaakko Tuomilehto, Sirkka Keinänen Kiukaanniemi, Ritva Vanninen, Seppo Helisalmi, Esko Levälahti, Miia Kivipelto, Hilkka Soininen, Alina Solomon

Abstract

Background: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile.

Objectives: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures.

Methods: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation.

Results: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (β-coefficient -0.29, p = 0.001) and hippocampal volume (β-coefficient -0.28, p = 0.003), lower cortical thickness (β-coefficient -0.19, p = 0.042), and poorer cognition (β-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p < 0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15, 95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation.

Conclusions: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.

Keywords: Aging; cognition; dementia; neuroimaging.

Figures

Fig.1
Fig.1
Overview of the study design.

References

    1. Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C (2014) Potential for primary prevention of Alzheimer’s disease, an analysis of population-based data. Lancet Neurol 13, 788–794.
    1. Tang EY, Harrison SL, Errington L, Gordon MF, Visser PJ, Novak G, Dufouil C, Brayne C, Robinson L, Launer LJ, Stephan BC (2015) Current developments in dementia risk prediction modelling, an updated systematic review. PLoS One 10, e0136181.
    1. Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M (2015) 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 385, 2255–2263.
    1. Moll van Charante EP, Richard E, Eurelings LS, van Dalen JW, Ligthart SA, van Bussel EF, Hoevenaar-Blom MP, Vermeulen M, van Gool WA (2016) Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): A cluster-randomised controlled trial. Lancet 388, 797–805.
    1. Andrieu S, Guyonnet S, Coley N, Cantet C, Bonnefoy M, Bordes S, Bories L, Cufi MN, Dantoine T, Dartigues JF, Desclaux F, Gabelle A, Gasnier Y, Pesce A, Sudres K, Touchon J, Robert P, Rouaud O, Legrand P, Payoux P, Caubere JP, Weiner M, Carrie I, Ousset PJ, Vellas B (2017) Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): A randomised, placebo-controlled trial. Lancet Neurol 16, 377–389.
    1. Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J (2006) Risk score for the prediction of dementia risk in 20 years among middle aged people, a longitudinal, population-based study. Lancet Neurol 5, 735–741.
    1. Exalto LG, Quesenberry CP, Barnes D, Kivipelto M, Biessels GJ, Whitmer RA (2014) Midlife risk score for the prediction of dementia four decades later. Alzheimers Dement 10, 562–570.
    1. Vuorinen M, Spulber G, Damangir S, Niskanen E, Ngandu T, Soininen H, Kivipelto M, Solomon A (2015) Midlife CAIDE dementia risk score and dementia-related brain changes up to 30 years later on magnetic resonance imaging. J Alzheimers Dis 44, 93–101.
    1. Enache D, Solomon A, Cavallin L, Kareholt I, Kramberger MG, Aarsland D, Kivipelto M, Eriksdotter M, Winblad B, Jelic V (2016) CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia. Neurobiol Aging 42, 124–131.
    1. Kaffashian S, Dugravot A, Elbaz A, Shipley MJ, Sabia S, Kivimaki M, Singh-Manoux A (2013) Predicting cognitive decline, a dementia risk score vs. the Framingham vascular risk scores. Neurology 80, 1300–1306.
    1. Reijmer YD, van den Berg E, van Sonsbeek S, Dekker JM, Nijpels G, Stehouwer CD, Kappelle LJ, Biessels GJ (2011) Dementia risk score predicts cognitive impairment after a period of 15 years in a nondemented population. Dement Geriatr Cogn Disord 31, 152–157.
    1. Kivipelto M, Solomon A, Ahtiluoto S, Ngandu T, Lehtisalo J, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J, Mangialasche F, Nissinen A, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H (2013) The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), study design and progress. Alzheimers Dement 9, 657–665.
    1. Ngandu T, Lehtisalo J, Levalahti E, Laatikainen T, Lindstrom J, Peltonen M, Solomon A, Ahtiluoto S, Antikainen R, Hanninen T, Jula A, Mangialasche F, Paajanen T, Pajala S, Rauramaa R, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M (2014) Recruitment and baseline characteristics of participants in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)-a randomized controlled lifestyle trial. Int J Environ Res Public Health 11, 9345–9360.
    1. Borodulin K, Vartiainen E, Peltonen M, Jousilahti P, Juolevi A, Laatikainen T, Mannisto S, Salomaa V, Sundvall J, Puska P (2015) Forty-year trends in cardiovascular risk factors in Finland. Eur J Public Health 25, 539–546.
    1. Tuomilehto H, Peltonen M, Partinen M, Seppa J, Saaristo T, Korpi-Hyovalti E, Oksa H, Saltevo J, Puolijoki H, Vanhala M, Tuomilehto J (2008) Sleep-disordered breathing is related to an increased risk for type 2 diabetes in middle-aged men, but not in women–the FIN-D2D survey. Diabetes Obes Metab 10, 468–475.
    1. Miettinen ME, Kinnunen L, Leiviska J, Keinanen-Kiukaanniemi S, Korpi-Hyovalti E, Niskanen L, Oksa H, Saaristo T, Tuomilehto J, Vanhala M, Uusitupa M, Peltonen M (2014) Association of serum 25-hydroxyvitamin D with lifestyle factors and metabolic and cardiovascular disease markers, population-based cross-sectional study (FIN-D2D). PLoS One 9, e100235.
    1. Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) (1989) Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology 39, 1159–1165.
    1. The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease), a major international collaboration (1988) WHO MONICA Project Principal Investigators. J Clin Epidemiol 41, 105–114.
    1. Tolonen H, Kuulasmaa K, Laatikainen T, Wolf H (2002) European Health Risk Monitoring Project. Recommendation for Indicators, International Collaboration, Protocol and Manual of Operations for Chronic Disease Risk Factor Surveys. Project EHRM Helsinki, Finland, National Public Health Institute.
    1. De la Vega FM, Lazaruk KD, Rhodes MD, Wenz MH (2005) Assessment of two flexible and compatible SNP genotyping platforms, TaqMan SNP Genotyping Assays and the SNPlex Genotyping System. Mutat Res 573, 111–135.
    1. Harrison J, Minassian SL, Jenkins L, Black RS, Koller M, Grundman M (2007) A neuropsychological test battery for use in Alzheimer disease clinical trials. Arch Neurol 64, 1323–1329.
    1. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state” (1975) A practical method for grading the cognitive state of patients forthe clinician. J Psychiatr Res 12, 189–198.
    1. Jack CR Jr, Wiste HJ, Weigand SD, Knopman DS, Mielke MM, Vemuri P, Lowe V, Senjem ML, Gunter JL, Reyes D, Machulda MM, Roberts R, Petersen RC (2015) Different definitions of neurodegeneration produce similar amyloid/neurodegeneration biomarker group findings. Brain 138, 3747–3759.
    1. Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, Kuiper M, Steinling M, Wolters EC, Valk J (1992) Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing, diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 55, 967–972.
    1. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 149, 351–356.
    1. Kemppainen NM, Aalto S, Wilson IA, Nagren K, Helin S, Bruck A, Oikonen V, Kailajärvi M, Scheinin M, Viitanen M, Parkkola R, Rinne JO (2006) Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Neurology 67, 1575–1580.
    1. Long SJ, Freese J (2014) Regression Models for Categorical Dependent Variables using Stata, 3rd ed Stata Press, College Station, TX.
    1. Schmidt R, Schmidt H, Haybaeck J, Loitfelder M, Weis S, Cavalieri M, Seiler S, Enzinger C, Ropele S, Erkinjuntti T, Pantoni L, Scheltens P, Fazekas F, Jellinger K (2011) Heterogeneity in age-related white matter changes. Acta Neuropathol 122, 171–185.
    1. Fagan AM (2015) What does it mean to be ‘amyloid-positive’? Brain 138, 514–516.
    1. Solomon A, Mangialasche F, Richard E, Andrieu S, Bennett DA, Breteler M, Breteler M, Fratiglioni L, Hooshmand B, Khachaturian AS, Schneider LS, Skoog I, Kivipelto M (2014) Advances in the prevention of Alzheimer’s disease and dementia. J Intern Med 275, 229–250.
    1. Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ (2013) Tracking pathophysiological processes in Alzheimer’s disease, an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12, 207–216.
    1. Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, Bakardjian H, Benali H, Bertram L, Blennow K, Broich K, Cavedo E, Crutch S, Dartigues JF, Duyckaerts C, Epelbaum S, Frisoni GB, Gauthier S, Genthon R, Gouw AA, Habert MO, Holtzman DM, Kivipelto M, Lista S, Molinuevo JL, O’Bryant SE, Rabinovici GD, Rowe C, Salloway S, Schneider LS, Sperling R, Teichmann M, Carrillo MC, Cummings J, Jack CR Jr (2016) Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement 12, 292–323.
    1. Schneider LS, Mangialasche F, Andreasen N, Feldman H, Giacobini E, Jones R, Mantua V, Mecocci P, Pani L, Winblad B, Kivipelto M (2014) Clinical trials and late-stage drug development for Alzheimer’s disease: An appraisal from 1984 to 2014. J Intern Med 275, 251–283.
    1. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, Cappa S, Crutch S, Engelborghs S, Frisoni GB, Fox NC, Galasko D, Habert MO, Jicha GA, Nordberg A, Pasquier F, Rabinovici G, Robert P, Rowe C, Salloway S, Sarazin M, Epelbaum S, de Souza LC, Vellas B, Visser PJ, Schneider L, Stern Y, Scheltens P, Cummings JL (2014) Advancing research diagnostic criteria for Alzheimer’sdisease, the IWG-2 criteria. Lancet Neurol 13, 614–629.
    1. Fjell AM, McEvoy L, Holland D, Dale AM, Walhovd KB, Alzheimer’s Disease Neuroimaging Initiative (2014) What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Prog Neurobiol 117, 20–40.
    1. Jack CR Jr, Wiste HJ, Knopman DS, Vemuri P, Mielke MM, Weigand SD, Senjem ML, Gunter JL, Lowe V, Gregg BE, Pankratz VS, Petersen RC (2014) Rates of beta-amyloid accumulation are independent of hippocampal neurodegeneration. Neurology 82, 1605–1612.
    1. Fotuhi M, Do D, Jack C (2012) Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol 8, 189–202.
    1. Chui HC, Zheng L, Reed BR, Vinters HV, Mack WJ (2012) Vascular risk factors and Alzheimer’s disease, are these risk factors for plaques and tangles or for concomitant vascular pathology that increases the likelihood of dementia? An evidence-based review. Alzheimers Res Ther 4, 1.
    1. Girouard H, Iadecola C (2006) Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol (1985) 100, 328–335.
    1. Chetelat G (2013) Alzheimer disease, Abeta-independent processes-rethinking preclinical AD. Nat Rev Neurol 9, 123–124.
    1. Han X, Jovicich J, Salat D, van der Kouwe A, Quinn B, Czanner S, Busa E, Pacheco J, Albert M, Killiany R, Maguire P, Rosas D, Makris N, Dale A, Dickerson B, Fischl B (2006) Reliability of MRI-derived measurements of human cerebral cortical thickness, the effects of field strength, scanner upgrade and manufacturer. Neuroimage 32, 180–194.
    1. Reuter M, Schmansky NJ, Rosas HD, Fischl B (2012) Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage 61, 1402–1418.

Source: PubMed

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