[en] Background. Cognitive complaints are gaining more attention as they may represent an early marker of increased risk for AD in individuals without objective decline at standard neuropsychological examination.
Objective. Our aim was to assess whether cognitive complaints in late middle-aged individuals not seeking medical help are related to objective cognitive outcomes known as early markers for AD risk, concomitant affective state, and amyloid-β (Aβ) burden.
Methods. Eighty-seven community-based cognitively normal individuals aged 50-69 years underwent neuropsychological assessment for global cognition, using Preclinical Alzheimer’s Cognitive Composite 5 (PACC5) score, and a more specific episodic memory measure. Affective state was based on self-assessment questionnaires for depression and anxiety. Aβ PET burden was assessed via [18F]Flutemetamol (N=84) and [18F]Florbetapir (N=3) uptake. Cognitive complaints were evaluated using Cognitive Difficulties Scale.
Results. Higher cognitive complaints were significantly associated with lower episodic memory performance and worse affective state. Moreover, higher level of cognitive complaints was related to higher (but still sub-clinical) global Aβ accumulation (at uncorrected significance level). Importantly, all three aspects remained significant when taken together in the same statistical model, indicating that they explained distinct parts of variance.
Conclusion. In healthy Aβ negative late middle-aged individuals, a higher degree of cognitive complaints is associated with lower episodic memory efficiency, more anxiety and depression, as well as, potentially, with higher Aβ burden, suggesting that complaints might signal subtle decline. Future studies should untangle how cognitive complaints in healthy aging populations are related to longitudinal changes in objective cognition and AD biomarker correlates.
Disciplines :
Neurosciences & behavior Neurology
Author, co-author :
Narbutas, Justinas ; Université de Liège - ULiège > GIGA-CRC In Vivo Imaging
Van Egroo, Maxime; Université de Liège - ULiège > GIGA-CRC In Vivo Imaging
Chylinski, Daphné ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Sleep and chronobiology
Bahri, Mohamed Ali ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Aging & Memory
Koshmanova, Ekaterina ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Sleep and chronobiology
Talwar, Puneet ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Sleep and chronobiology
Besson, Gabriel ; Université de Liège - ULiège > CRC In vivo Imaging-Aging & Memory
Muto, Vincenzo ; Université de Liège - ULiège > GIGA CRC In vivo Imaging
Schmidt, Christina ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Sleep and chronobiology
Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences) > Département de chimie (sciences)
Balteau, Evelyne ; Université de Liège - ULiège > GIGA CRC In vivo Im. - Neuroimaging, data acquisi. & proces.
Phillips, Christophe ; Université de Liège - ULiège > GIGA CRC In vivo Im. - Neuroimaging, data acquisi. & proces.
MAQUET, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de neurologie
Salmon, Eric ; Université de Liège - ULiège > Département des sciences cliniques > Neuroimagerie des troubles de la mémoire et revalid. cogn.
Bastin, Christine ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Aging & Memory
Vandewalle, Gilles ; Université de Liège - ULiège > GIGA CRC In vivo Imaging - Sleep and chronobiology
Collette, Fabienne ; Université de Liège - ULiège > Département de Psychologie > Neuropsychologie
Associations between cognitive complaints, memory performance, mood and amyloid-β accumulation in healthy amyloid negative late-midlife individuals
Publication date :
2021
Journal title :
Journal of Alzheimer's Disease
ISSN :
1387-2877
eISSN :
1875-8908
Volume :
83
Pages :
127-141
Peer reviewed :
Peer reviewed
Name of the research project :
Cognitive Fitness in Aging study ERDF, Radiomed Project
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique WBI - Wallonia-Brussels International ULiège - Université de Liège Fondation Pierre et Simone Clerdent ERDF - European Regional Development Fund ERC - European Research Council
Funding number :
Fonds National de la Recherche Scientifique (FRS-FNRS, FRSM 3.4516.11, MEMODYN 30446199, Belgium); Wallonia-Brussels Federation (grant for Concerted Research Actions – grant 17/21-09 SLEEPDEM); SAO-FRA (grant 15018); European Research Council starting grant (CS; ERC-StG 757763)
Funding text :
[18F]Flutemetamol doses were provided and cost covered by GE Healthcare Ltd (Little Chalfont, UK) as part of an investigator sponsored study (ISS290) agreement. This agreement had no influence on the protocol and results of the study reported here
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7, 263-269.
Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Associationworkgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7, 280-292.
Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R, Elliott C, Masliah E, Ryan L, Silverberg N(2018) NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 14, 535-562.
Jessen F, Amariglio RE, Van Boxtel M, Breteler M, Ceccaldi M, Chételat G, Dubois B, Dufouil C, Ellis KA, Van Der Flier WM, Glodzik L, Van Harten AC, De Leon MJ, McHugh P, Mielke MM, Molinuevo JL, Mosconi L, Osorio RS, Perrotin A, Petersen RC, Rabin LA, Rami L, Reisberg B, Rentz DM, Sachdev PS, De La Sayette V, Saykin AJ, Scheltens P, Shulman MB, Slavin MJ, Sperling RA, Stewart R, Uspenskaya O,Vellas B,Visser PJ,Wagner M(2014) A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease. Alzheimers Dement 10, 844-852.
Rabin LA, Smart CM, Crane PK, Amariglio RE, Berman LM, Boada M, Buckley RF, Chételat G, Dubois B, Ellis KA, Gifford KA, Jefferson AL, Jessen F, Katz MJ, Lipton RB, Luck T, Maruff P, Mielke MM, Molinuevo JL, Naeem F, Perrotin A, Petersen RC, Rami L, Reisberg B, Rentz DM, Riedel-Heller SG, Risacher SL, Rodriguez O, Sachdev PS, Saykin AJ, Slavin MJ, Snitz BE, Sperling RA, Tandetnik C, van der Flier WM, Wagner M, Wolfsgruber S, SikkesSAM(2015) Subjective cognitive decline in older adults: An overview of self-report measures used across 19 international research studies. J Alzheimers Dis 48(Suppl 1), S63-86.
Jessen F, Wiese B, Bachmann C, Eifflaender-Gorfer S (2010) Prediction of dementia by subjective memory impairment. Arch Gen Psychiatry 67, 414-422.
Garcia-Ptacek S, Cavallin L, Kareholt I, Kramberger MG, Winblad B, Jelic V, Eriksdotter M (2014) Subjective cognitive impairment subjects in our clinical practice. Dement Geriatr Cogn Dis Extra 4, 419-30.
Jacinto A, Brucki S, Porto C, Martins M, Nitrini R (2014) Subjective memory complaints in the elderly: A sign of cognitive impairment? Clinics (Sao Paulo) 69, 194-197.
Langlois AS, Belleville S (2014) Subjective cognitive complaint in healthy older adults: Identification of major domains and relation to objective performance. Aging Neuropsychol Cogn 21, 257-282.
McNair DM, Kahn RJ (1984) Self-assessment of cognitive deficits. In Assessment in geriatric psychopharmacology, Crook T, Ferris S, Bartus R, eds. Mark Powley, New Canaan.
Farias ST, Mungas D, Reed BR, Cahn-Weiner D, JagustW, Baynes K, Decarli C (2008) The measurement of everyday cognition (ECog): Scale development and psychometric properties. Neuropsychology 22, 531-44.
Rattanabannakit C, Risacher SL, Gao S, Lane KA, Brown SA, McDonald BC, Unverzagt FW, Apostolova LG, Saykin AJ, FarlowMR (2016) The cognitive change index as a measure of self and informant perception of cognitive decline: Relation to neuropsychological tests. J Alzheimers Dis 51, 1145-1155.
Rami L, Mollica MA, Garcfa-Sanchez C, Saldafia J, Sanchez B, Sala I, Valls-Pedret C, Castellvi M, Olives J, Molinuevo JL (2014) The subjective cognitive decline questionnaire (SCD-Q): A validation study. J Alzheimers Dis 41, 453-466.
Miebach L, Wolfsgruber S, Polcher A, Peters O, Menne F, Luther K, Incesoy E, Priller J, Spruth E, Altenstein S, Buerger K, Catak C, Janowitz D, Perneczky R, Utecht J, Laske C, Buchmann M, Schneider A, Fliessbach K, Kalbhen P, Heneka MT, Brosseron F, Spottke A, Roy N, Teipel SJ, Kilimann I, Wiltfang J, Bartels C, D¨uzel E, Dobisch L, Metzger C, Meiberth D, Ramirez A, Jessen F, Wagner M (2019) Which features of subjective cognitive decline are related to amyloid pathology? Findings from the DELCODE study. Alzheimers Res Ther 11, 66.
Ferreira D, Machado A, Molina Y, Nieto A, Correia R, Westman E, Barroso J (2017) Cognitive variability during middle-age: Possible association with neurodegeneration and cognitive reserve. Front Aging Neurosci 9, 188.
Jessen F, Amariglio RE, Buckley RF, van der Flier WM, Han Y, Molinuevo JL, Rabin L, Rentz DM, Rodriguez-Gomez O, Saykin AJ, Sikkes SAM, Smart CM, Wolfsgruber S, Wagner M (2020) The characterisation of subjective cognitive decline. Lancet Neurol 19, 271-278.
Sachdev PS, Blacker D, Blazer DG, Ganguli M, Jeste D V., Paulsen JS, Petersen RC (2014) Classifying neurocognitive disorders: The DSM-5 approach. Nat Rev Neurol 10, 634-642.
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington, DC.
Slot RER, Sikkes SAM, Berkhof J, Brodaty H, Buckley R, Cavedo E, Dardiotis E, Guillo-Benarous F, Hampel H, Kochan NA, Lista S, Luck T, Maruff P, Molinuevo JL, Kornhuber J, Reisberg B, Riedel-Heller SG, Risacher SL, Roehr S, Sachdev PS, Scarmeas N, Scheltens P, Shulman MB, Saykin AJ, Verfaillie SCJ, Visser PJ, Vos SJB, Wagner M, Wolfsgruber S, Jessen F, Boada M, de Deyn PP, Jones R, Frisoni G, Spiru L, Nobili F, Freund-Levi Y, Soininen H, Verhey F, Wallin A K, Touchon J, Rikkert MO, Rigaud AS, Bullock R, Tsolaki M, Vellas B,Wilcock G, Froelich L, Bakardjian H, Benali H, Bertin H, Bonheur J, Boukadida L, Boukerrou N, Chiesa P, Colliot O, Dubois B, Dubois M, Epelbaum S, Gagliardi G, Genthon R, Habert MO, Houot M, Kas A, Lamari F, Levy M, Metzinger C, Mochel F, Nyasse F, Poisson C, Potier MC, Revillon M, Santos A, Andrade KS, Sole M, Surtee M, Thiebaud de Schotten M, Vergallo A, Younsi N, van der FlierWM(2019) Subjective cognitive decline and rates of incident Alzheimer's disease and non-Alzheimer's disease dementia. Alzheimers Dement 15, 465-476.
Waldorff FB, Rishoj S, Waldemar G (2008) If you don't ask (about memory), they probablywon't tell. J Fam Pract 57, 41-44.
Ritchie K, Ritchie CW, Jaffe K, Skoog I, Scarmeas N (2015) Is late-onset Alzheimer's disease really a disease of midlife? Alzheimers Dement (N Y) 1, 122-130.
Jack CR, Holtzman DM (2013) Biomarker modeling of Alzheimer's disease. Neuron 80, 1347-1358.
Beason-Held LL, Goh JO, An Y, Kraut MA, O'Brien RJ, Ferrucci L, Resnick SM (2013) Changes in brain function occur years before the onset of cognitive impairment. J Neurosci 33, 18008-18014.
Coupé P, Manjón JV, Lanuza E, Catheline G (2019) Lifespan changes of the human brain in Alzheimer's disease. Sci Rep 9, 3998.
Eckert (2010) Age-related changes in processing speed: Unique contributions of cerebellar and prefrontal cortex. Front Hum Neurosci 4, 10.
Fjell AM, Sneve MH, Grydeland H, Storsve AB,Walhovd KB (2017) The disconnected brain and executive function decline in aging. Cereb Cortex 27, 2303-2317.
Harada CN, Natelson Love MC, Triebel KL (2013) Normal cognitive aging. Clin Geriatr Med 29, 737-752.
Hoogendam YY, Hofman A, Van Der Geest JN, Van Der Lugt A, IkramMA(2014) Patterns of cognitive function in aging: The Rotterdam Study. Eur J Epidemiol 29, 133-140.
Olaya B, Bobak M, Haro JM, Demakakos P (2017) Trajectories of verbal episodic memory in middle-aged and older adults: Evidence from the English Longitudinal Study of Ageing. J Am Geriatr Soc 65, 1274-1281.
R¨onnlund M, Nyberg L, B¨ackman L, Nilsson L-G (2005) Stability, growth, and decline in adult life span development of declarative memory: Cross-sectional and longitudinal data from a population-based study. Psychol Aging 20, 3-18.
Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, Jackson JD, Mormino EC, Rentz DM, Sperling RA, Johnson KA, Amariglio RE (2017) Region-specific association of subjective cognitive decline with tauopathy independent of global-amyloid burden. JAMA Neurol 74, 1455-1463.
Amariglio RE, Mormino EC, Pietras AC, Marshall GA, Vannini P, Johnson KA, Sperling RA, Rentz DM (2015) Subjective cognitive concerns, amyloid-, and neurodegeneration in clinically normal elderly. Neurology 85, 56-62.
Zwan MD, Villemagne VL, Doré V, Buckley R, Bourgeat P,Veljanoski R, Salvado O,Williams R, Margison L, Rembach A, Macaulay SL, Martins R, Ames D, Van Der Flier WM, Ellis KA, Scheltens P, Masters CL, Rowe CC (2016) Subjective memory complaints in APOE 4 carriers are associated with high amyloid-burden. J Alzheimers Dis 49, 1115-1122.
Teipel SJ, Cavedo E, Weschke S, Grothe MJ, Rojkova K, Fontaine G, Dauphinot L, Gonzalez-Escamilla G, Potier MC, Bertin H, Habert MO, Dubois B, Hampel H, Christelle A, Hugo B, Laurie B, Federica C, Enrica C, Patrizia CA, Stanley D, Stephane E, Geoffroy G, Remy G, Pailine G, Aurelie K, Marcel L, Simone L, Christiane M, Francis N, Catherine P, Stephie R, Marie R, Katrine R, Perrine R, Katia SA, Antonio S, Valérie S, Marine S, Caroline T, Bruno D, Harald H, Hovagim B, Habib B, Olivier C, Marie-Odile H, Foudil L, Fanny M, Marie-Claude P, de Schotten Michel T (2017) Cortical amyloid accumulation is associated with alterations of structural integrity in older people with subjective memory complaints. Neurobiol Aging 57, 143-152.
Shokouhi S, Conley AC, Baker SL, Albert K, Kang H, Gwirtsman HE, Newhouse PA (2019) The relationship between domain-specific subjective cognitive decline and Alzheimer's pathology in normal elderly adults. Neurobiol Aging 81, 22-29.
Mielke MM, Wiste HJ, Stephen Weigand BD, David Knopman MS, Lowe VJ, Roberts RO, Yonas Geda ME, Swenson-Dravis DM, Bradley Boeve MF, Senjem ML, Prashanthi Vemuri B, Petersen RC, Jack CR (2012) Indicators of amyloid burden in a population-based study of cognitively normal elderly. Neurology 79, 1570-1577.
Toledo JB, Bjerke M, Chen K, Rozycki M, Jack CR Jr, WeinerMW, Arnold SE, Reiman EM, Davatzikos C, Shaw LM, Trojanowski JQ; Alzheimer's Disease Neuroimaging Initiative (2015) Memory, executive, and multidomain subtle cognitive impairment: Clinical and biomarker findings. Neurology 85, 144-53.
Mosconi L, De Santi S, Brys M, Tsui WH, Pirraglia E, Glodzik-Sobanska L, Rich KE, Switalski R, Mehta PD, Pratico D, Zinkowski R, Blennow K, de Leon MJ (2008) Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. Biol Psychiatry 63, 609-618.
Grambaite R, Hessen E, Auning E, Aarsland D, Selnes P, Fladby T (2013) Correlates of subjective and mild cognitive impairment: Depressive symptoms and CSF biomarkers. Dement Geriatr Cogn Dis Extra 3, 291-300.
Weisenbach SL, Boore LA, Kales HC (2012) Depression and cognitive impairment in older adults. Curr Psychiatry Rep 14, 280-288.
Hill NL, Mogle J, Wion R, Munoz E, DePasquale N, Yevchak AM, Parisi JM (2016) Subjective cognitive impairment and affective symptoms: A systematic review. Gerontologist 56, e109-e127.
Sun Y, Wang X, Wang Y, Dong H, Lu J, Scheininger T, Ewers M, Jessen F, Zuo XN, Han Y (2019) Anxiety correlates with cortical surface area in subjective cognitive decline: APOE 4 carriers versus APOE 4 non-carriers. Alzheimers Res Ther 11, 50.
Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, Ballard C, Banerjee S, Burns A, Cohen-Mansfield J, Cooper C, Fox N, Gitlin LN, Howard R, Kales HC, Larson EB, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbæk G, Teri L, Mukadam N (2017) Dementia prevention, intervention, and care. Lancet 390, 2673-2734.
Hurt CS, Burns A, Brown RG, Barrowclough C (2012) Why don't older adults with subjective memory complaints seek help? Int J Geriatr Psychiatry 27, 394-400.
Narbutas J, Van Egroo M, Chylinski D, González PV, Jimenez CG, Besson G, Ghaemmaghami P, Hammad G, Muto V, Schmidt C, Luxen A, Salmon E, Maquet P, Bastin C, Vandewalle G, Collette F (2019) Cognitive efficiency in late midlife is linked to lifestyle characteristics and allostatic load. Aging (Albany NY) 11, 7169-7186.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4, 561-571.
Beck AT, Epstein N, Brown G, Steer RA (1988) An inventory for measuring clinical anxiety: Psychometric properties. J Consult Clin Psychol 56, 893-897.
Mattis (1976) Mental status examination for organic mental syndrome in the elderly patients. In Geriatrics Psychiatry: A Handbook for Psychiatrists and Primary Care Physicians, Bellak L, Karasu T, New York, pp. 77-121.
Donohue MC, Sperling RA, Salmon DP, Rentz DM, Raman R, Thomas RG, Weiner M, Aisen PS (2014) The preclinical Alzheimer cognitive composite: Measuring amyloid-related decline. JAMA Neurol 71, 961-970.
Papp KV, Rentz DM, Orlovsky I, Sperling RA, Mormino EC (2017) Optimizing the preclinical Alzheimer's cognitive composite with semantic processing: The PACC5. Alzheimers Dement (N Y) 3, 668-677.
Grober E, Hall CB, Lipton RB, Alan B, Resnick SM, Kawas C (2009) NIH Public Access. J Int Neuropsychol Soc 14, 266-278.
Wechsler D, Stone CP (1987) Wechsler Memory Scalerevised, Psychological Corporation, San Antonio.
WechslerD(1981)WAIS-R Manual:Wechsler Adult Intelligence Scale-Revised, Psychological Corporation, San Antonio.
FolsteinMF, Folstein SE,McHughPR(1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12, 189-198.
Wechsler D (1997) The WAIS III-WMS III Technical Manual, Psychological Corporation, San Antonio.
Ritchie K, Ropacki M, Albala B, Harrison J, Kaye J, Kramer J, Randolph C, RitchieCW(2017) Recommended cognitive outcomes in preclinical Alzheimer's disease: Consensus statement from the European Prevention of Alzheimer's Dementia project. Alzheimers Dement 13, 186-195.
Perrotin A, La Joie R, de La Sayette V, Barré L, Mézenge F, Mutlu J, Guilloteau D, Egret S, Eustache F, Chételat G (2017) Subjective cognitive decline in cognitively normal elders from the community or from a memory clinic: Differential affective and imaging correlates. Alzheimers Dement 13, 550-560.
La Joie R, Perrotin A, Egret S, Pasquier F, Tomadesso C, Mézenge F, Desgranges B, de La Sayette V, Chételat G (2016) Qualitative and quantitative assessment of selfreported cognitive difficulties in nondemented elders: Association with medical help seeking, cognitive deficits, and-amyloid imaging. Alzheimers Dement (Amst) 5, 23-34.
Weiskopf N, HelmsG(2008) Multi-parameter mapping of the human brain at1mmresolution in less than 20 minutes. Proc Int Soc Magn Reson Med 16, 2241.
Tabelow K, Balteau E, Ashburner J, Callaghan MF, Draganski B, Helms G, Kherif F, Leutritz T, Lutti A, Phillips C, Reimer E, Ruthotto L, Seif M, Weiskopf N, Ziegler G, Mohammadi S (2019) hMRI-A toolbox for quantitative MRI in neuroscience and clinical research. Neuroimage 194, 191-210.
Ashburner J (2007) A fast diffeomorphic image registration algorithm. Neuroimage 38, 95-113.
Klunk WE, Koeppe RA, Price JC, Benzinger TL, Devous MD, Jagust WJ, Johnson KA, Mathis CA, Minhas D, Pontecorvo MJ, Rowe CC, Skovronsky DM, Mintun MA (2015) The Centiloid project: Standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement 11, 1-15.e4.
Rolls ET, Joliot M, Tzourio-MazoyerN(2015) Implementation of a new parcellation of the orbitofrontal cortex in the automated anatomical labeling atlas. Neuroimage 122, 1-5.
Navitsky M, Joshi AD, Kennedy I, Klunk WE, Rowe CC, Wong DF, Pontecorvo MJ, Mintun MA, Devous MD (2018) Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale. Alzheimers Dement 14, 1565-1571.
Battle MR, Pillay LC, Lowe VJ, Knopman D, Kemp B, Rowe CC, Doré V, Villemagne VL, Buckley CJ (2018) Centiloid scaling for quantification of brain amyloid with [ 18 F]flutemetamol using multiple processing methods. EJNMMI Res 8, 107.
Narbutas J, Chylinski D, Egroo M Van, Bahri MA, Koshmanova E, Besson G, Muto V, Schmidt C, Luxen A, Balteau E, Phillips C, Maquet P, Salmon E, Vandewalle G, Bastin C, Collette F, Snow AD (2021) Positive effect of cognitive reserve on episodic memory, executive and attentional functions taking into account amyloid-beta, tau, and apolipoprotein E status. Front Aging Neurosci 13, 666181.
Insel PS, Mormino EC, Aisen PS, Thompson WK, Donohue MC (2020) Neuroanatomical spread of amyloid and tau in Alzheimer's disease: Implications for primary prevention. Brain Commun 2, fcaa007.
Auton A, Abecasis GR, Altshuler DM, Durbin RM, Bentley DR, Chakravarti A, Clark AG, Donnelly P, Eichler EE, Flicek P, et al. (2015)Aglobal reference for human genetic variation. Nature 526, 68-74.
Loh PR, Danecek P, Palamara PF, Fuchsberger C, Reshef YA, Finucane HK, Schoenherr S, Forer L, McCarthy S, Abecasis GR, Durbin R, Price AL (2016) Reference-based phasing using the Haplotype Reference Consortium panel. Nat Genet 48, 1443-1448.
Sadegh M, Ragno E, AghaKouchak A (2017) Multivariate Copula Analysis Toolbox (MvCAT): Describing dependence and underlying uncertainty using a Bayesian framework. Water Resour Res 53, 5166-5183.
Jaeger BC, Edwards LJ, Das K, Sen PK (2017) An R 2 statistic for fixed effects in the generalized linear mixed model. J Appl Stat 44, 1086-1105.
Dauphinot V, Bouteloup V, Mangin J, Vellas B, Pasquier F, Blanc F, Hanon O, Gabelle A, Annweiler C, David R, Planche V, Godefroy O, Rivasseau-Jonveaux T, Chupin M, Fischer C, Chene G, Dufouil C, Krolak-Salmon P (2020) Subjective cognitive and non-cognitive complaints and brain MRI biomarkers in the MEMENTO cohort. Alzheimers Dement (Amst) 12, e12051.
de Jager CA, Schrijnemaekers A-CMC, Honey TEM, BudgeMM(2009) Detection of MCI in the clinic: Evaluation of the sensitivity and specificity of a computerised test battery, the Hopkins Verbal Learning Test and the MMSE. Age Ageing 38, 455-460.
Calabria M, Manenti R, Rosini S, Zanetti O, Miniussi C, CotelliM(2011) Objective and subjective memory impairment in elderly adults: A revised version of the Everyday Memory Questionnaire. Aging Clin Exp Res 23, 67-73.
Pelletier A, Bernard C, Dilharreguy B, Helmer C, Le Goff M, Chanraud S, Dartigues JF, Allard M, Amieva H, Gwénäelle C (2017) Patterns of brain atrophy associated with episodic memory and semantic fluency decline in aging. Aging (Albany NY) 9, 1470.
Jeong W, Chung CK, Kim JS (2015) Episodic memory in aspects of large-scale brain networks. Front Hum Neurosci 9, 454.
Hollands S, Lim YY, Buckley R, Pietrzak RH, Snyder PJ, Ames D, Ellis KA, Harrington K, Lautenschlager N, Martins RN, Masters CL, Villemagne VL, Rowe CC, Maruff P (2015) Amyloid-related memory decline is not associated with subjective or informant rated cognitive impairment in healthy adults. J Alzheimers Dis 43, 677-686.
Snitz BE, Lopez OL, McDade E, Becker JT, Cohen AD, Price JC, Mathis CA, KlunkWE(2015) Amyloid-imaging in older adults presenting to a memory clinic with subjective cognitive decline: A pilot study. J Alzheimers Dis 48, S151-S159.
Amariglio RE, Becker JA, Carmasin J (2012) Subjective cognitive complaints and amyloid burden in cognitively normal older individuals. Neuropsychologia 50, 2880-2886.
Perrotin A (2012) Subjective cognition and amyloid deposition imaging. Arch Neurol 69, 223.
Snitz BE,Weissfeld LA, Cohen AD, Lopez OL, Nebes RD, Aizenstein HJ, McDade E, Price JC, Mathis CA, Klunk WE (2015) Subjective cognitive complaints, personality and brain amyloid-beta in cognitively normal older adults. Am J Geriatr Psychiatry 23, 985-993.
Gonzalez-Escamilla G, Lange C, Teipel S, Buchert R, Grothe MJ (2017) PETPVE12: An SPM toolbox for partial volume effects correction in brain PET-Application to amyloid imaging with AV45-PET. Neuroimage 147, 669-677.
Su Y, Blazey TM, Snyder AZ, Raichle ME, Marcus DS, Ances BM, Bateman RJ, Cairns NJ, Aldea P, Cash L, Christensen JJ, Friedrichsen K, Hornbeck RC, Farrar AM, Owen CJ, Mayeux R, Brickman AM, Klunk W, Price JC, Thompson PM, Ghetti B, Saykin AJ, Sperling RA, Johnson KA, Schofield PR, Buckles V, Morris JC, Benzinger TLS (2015) Partial volume correction in quantitative amyloid imaging. Neuroimage 107, 55-64.
Spencer RJ,Wendell CR, Giggey PP, Katzel LI, Lefkowitz DM, Siegel EL, Waldstein SR (2013) Psychometric lim itations of the mini-mental state examination among nondemented older adults: An evaluation of neurocognitive and magnetic resonance imaging correlates. Exp Aging Res 39, 382-397.
Lim YY, Snyder PJ, Pietrzak RH, Ukiqi A, Villemagne VL, Ames D, Salvado O, Bourgeat P, Martins RN, Masters CL, Rowe CC, Maruff P (2016) Sensitivity of composite scores to amyloid burden in preclinical Alzheimer's disease: Introducing the Z-scores of Attention, Verbal fluency, and Episodic memory for Nondemented older adults composite score. Alzheimers Dement (Amst) 2, 19-26.
Chen G,Yang K, DuW, Hu X, HanY(2019) Clinical characteristics in subjective cognitive decline with and without worry: Baseline investigation of the SILCODE Study. J Alzheimers Dis 72, 443-454.
Iob E, Kirschbaum C, Steptoe A (2020) Persistent depressive symptoms,HPA-axis hyperactivity, and inflammation: The role of cognitive-affective and somatic symptoms. Mol Psychiatry 25, 1130-1140.
Hertzog C, H¨ul¨ur G, Gerstorf D, Pearman AM (2018) Is subjective memory change in old age based on accurate monitoring of age-related memory change? Evidence from two longitudinal studies. Psychol Aging 33, 273-287.
van Oijen M, de Jong FJ, Hofman A, Koudstaal PJ, Breteler MMB (2007) Subjective memory complaints, education, and risk of Alzheimer's disease. Alzheimers Dement 3, 92-97.
Amieva H, Mokri H, Le Goff M, Meillon C, Jacqmin-Gadda H, Foubert-Samier A, Orgogozo JM, Stern Y, Dartigues JF (2014) Compensatory mechanisms in highereducated subjects with Alzheimer's disease: A study of 20 years of cognitive decline. Brain 137, 1167-1175.
SternY, Arenaza-Urquijo EM, Bartrés-Faz D, Belleville S, Cantilon M, Chetelat G, Ewers M, Franzmeier N,Kempermann G, KremenWS,OkonkwoO, Scarmeas N, Soldan A, Udeh-Momoh C, Valenzuela M, Vemuri P, Vuoksimaa E, Arenaza Urquiljo EM, Bartrés-Faz D, Belleville S, Cantillon M, Chetelat G, Clouston SAP, Estanga A, Ewers M, Franzmeier N, Gold B, Habeck C, Jones R, Kempermann G,Kochhann R, KremenW, LimYY, Martínez-Lage P, Morbelli S, Okonkwo O, Ossenkoppele R, Pettigrew C, Rosen AC, Scarmeas N, Soldan A, Song X, Udeh-Momoh C, Stern Y, Valenzuela M, Van Loenhoud AC, Vemuri P, Vuoksimaa E (2020) Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement 16, 1305-1311.
Aghjayan SL, Buckley RF, Vannini P, Rentz DM, Jackson JD, Sperling RA, Johnson KA, Amariglio RE (2017) The influence of demographic factors on subjective cognitive concerns and beta-amyloid. Int Psychogeriatr 29, 645-652.
Ali JI, Smart CM, Gawryluk JR (2018) Subjective cognitive decline and APOE 4: A systematic review. J Alzheimers Dis 65, 303-320.
Moreno-Grau S, Rodríguez-Gómez O, Sanabria Á , Pérez-Cordón A, Sánchez-Ruiz D, Abdelnour C, Valero S, Hernández I, Rosende-Roca M, Mauleón A, Vargas L, Lafuente A, Gil S, Santos-Santos MÁ , Alegret M, Espinosa A, Ortega G, Guitart M, Gailhajanet A, de Rojas I, Sotolongo-Grau Ó , Ruiz S, Aguilera N, Papasey J, Martín E, Peleja E, Lomena F, Campos F, Vivas A, Gómez-Chiari M, Tejero MÁ , Giménez J, Serrano-Riós M, Orellana A, Tárraga L, Ruiz A, Boada M, Abdelnour C, Aguilera N, Alegret M, Berthier M, Boada M, Buendia M, Bullich S, Campos F, Canabate P, Cuevas C, de Rojas I, Espinosa A, Gailhajenet A, Diego S, Gil S, Giménez J, Gismondi R, Gómez-Chiari M, Guitart M, Hernández-Olasagarre B, Hernández I, Ibarria M, Lafuente A, Lomena F, Martín E, Martínez J, Mauleón A, Monté G, Moreno M, Moreno-Grau S, Núnez L, Orellana A, Ortega G, Paéz A, Pancho A, Paviá J, Peleja E, Pérez-Cordon A, Pérez-Grijalba V, Pesini P, Preckler S, Rodríguez-Gómez O, Romero J, Rosende-Roca M, Ruiz A, Ruiz S, Sanabria A, Sánchez-Ruiz D, Santos-Santos MA, Sarasa M, Sotolongo-Grau O, Tárraga L, Tejero MA, Torres M, Valero S, Vargas L, Vivas A (2018) Exploring APOE genotype effects on Alzheimer's disease risk and amyloid burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results. Alzheimers Dement 14, 634-643.
M¨uller-Gerards D, Weimar C, Abramowski J, Tebr¨ugge S, Jokisch M, Dragano N, Erbel R, J¨ockel KH, Moebus S, Winkler A (2019) Subjective cognitive decline, APOE 4, and incident mild cognitive impairment in men and women. Alzheimers Dement (Amst) 11, 221-230.
Wang L, Van Belle G, Crane PK, Kukull WA, Bowen JD, McCormick WC, Larson EB (2004) Subjective memory deterioration and future dementia in people aged 65 and older. J Am Geriatr Soc 52, 2045-2051.
Cantero JL, Iglesias JE,Van Leemput K, AtienzaM(2016) Regional hippocampal atrophy and higher levels of plasma amyloid-beta are associated with subjective memory complaints in nondemented elderly subjects. J Gerontol A Biol Sci Med Sci 71, 1210-1215.
de Leeuw FA, van der Flier WM, Tijms BM, Scheltens P, Mendes VM, Manadas B, Bierau J, van Wijk N, van den Heuvel EGHM, Mohajeri MH, Teunissen CE, Kester MI (2020) Specific nutritional biomarker profiles in mild cognitive impairment and subjective cognitive decline are associated with clinical progression: TheNUDADProject. J Am Med Dir Assoc 21, 1513.e1-1513.e17.
Palomar-Bonet M, Atienza M, Cantero JL (2020) Blood total antioxidant status is associated with cortical glucose uptake and factors related to accelerated aging. Brain Struct Funct 225, 841-851.
Janelidze S, Berron D, Smith R, Strandberg O, Proctor NK, Dage JL, Stomrud E, Palmqvist S, Mattsson-Carlgren N, Hansson O (2021) Associations of plasma phospho-Tau217 levels with tau positron emission tomography in early Alzheimer disease. JAMA Neurol 78, 149-156.
Welstead M, Luciano M, Muniz-Terrera G, Saunders S, Mullin DS, Russ TC (2021) Predictors of mild cognitive impairment stability, progression, or reversion in the Lothian Birth Cohort 1936. J Alzheimers Dis 80, 225-232.
Hanseeuw BJ, Betensky RA, Jacobs HIL, Schultz AP, Sepulcre J, Becker JA, Cosio DMO, Farrell M, Quiroz YT, Mormino EC, Buckley RF, Papp KV, Amariglio RA, Dewachter I, Ivanoiu A, Huijbers W, Hedden T, Marshall GA, Chhatwal JP, Rentz DM, Sperling RA, Johnson K (2019) Association of amyloid and tau with cognition in preclinical Alzheimer disease:Alongitudinal study. JAMA Neurol 76, 915-924.
