[en] Neuropsychiatric symptoms (NPS) have been associated with a risk of accelerated cognitive decline or conversion to dementia of the Alzheimer’s Disease (AD) type. Moreover, the NPS were also associated with higher AD biomarkers (brain tau and amyloid burden) even in non-demented patients. But the effect of the relationship between NPS and biomarkers on cognitive decline has not yet been studied. This work aims to assess the relationship between longitudinal cognitive changes and NPS, specifically depression and anxiety, in association with AD biomarkers in healthy middle-aged to older participants. The cohort consisted of 101 healthy participants aged 50–70 years, 66 of whom had neuropsychological assessments of memory, executive functions, and global cognition at a 2-year follow-up. At baseline, NPS were assessed using the Beck Depression and Anxiety Inventories while brain tau and amyloid loads were measured using positron emission topography. For tau burden, THK5351 uptake is used as a proxy of tau and neuroinflammation. Participants, declining or remaining stable at follow-up, were categorized into groups for each cognitive domain. Group classification was investigated using binary logistic regressions based on combined AD biomarkers and the two NPS. The results showed that an association between anxiety and prefrontal amyloid burden significantly classified episodic memory decline, while the classification of global cognitive decline involved temporal and occipital amyloid burden but not NPS. Moreover, depression together with prefrontal and hippocampal tau burden were associated with a decline in memory. The classification of participants based on executive decline was related to depression and mainly prefrontal tau burden. These findings suggest that the combination of NPS and brain biomarkers of AD predicts the occurrence of cognitive decline in aging.
Disciplines :
Neurosciences & comportement
Auteur, co-auteur :
Ronat, Lucas
Hanganu, Alexandru
Chylinski, Daphné ; Université de Liège - ULiège > GIGA > GIGA CRC In vivo Imaging - Physiology of Cognition
Van Egroo, Maxime
Narbutas, Justinas ; Université de Liège - ULiège > Département de Psychologie > Neuropsychologie de l'adulte
Besson, Gabriel ; Université de Liège - ULiège > GIGA > GIGA CRC In vivo Imaging - Aging & Memory
Muto, Vincenzo ; Université de Liège - ULiège > GIGA > GIGA CRC In vivo Imaging
Schmidt, Christina ; Université de Liège - ULiège > Département de Psychologie > Neuropsychologie de l'adulte
Mitacs F.R.S.-FNRS - Fonds de la Recherche Scientifique FWB - Fédération Wallonie-Bruxelles
Subventionnement (détails) :
For this project, Lucas Ronat received a grant from the MITACS Globalink program. This work was supported by the Fonds National de la Recherche Scientifique (CS is a research associate, CB and GV are senior research associates, and FC and CP are research directors at the FRS-FNRS) and by the Wallonia-Brussels Federation (Concerted Research Actions – grant 17/21-09 SLEEPDEM).
Y.E. Geda R.O. Roberts D.S. Knopman et al. Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study Arch Gen Psychiatry 2008 65 1193 1198 10.1001/archpsyc.65.10.1193 18838636 2575648
M.E. Mortby Z. Ismail K.J. Anstey Prevalence estimates of mild behavioral impairment in a population-based sample of pre-dementia states and cognitively healthy older adults Int Psychogeriatr 2018 30 221 232 10.1017/S1041610217001909 28931446
Y.E. Geda G.E. Smith D.S. Knopman et al. De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI) Int Psychogeriatr 2004 16 51 60 10.1017/S1041610204000067 15190996
P.B. Rosenberg M.M. Mielke B.S. Appleby et al. The association of neuropsychiatric symptoms in MCI with incident dementia and alzheimer disease Am J Geriatr Psychiatry 2013 21 685 695 10.1016/j.jagp.2013.01.006 23567400
M.H. Burhanullah J.T. Tschanz M.E. Peters et al. Neuropsychiatric symptoms as risk factors for cognitive decline in clinically normal older adults: the Cache county study Am J Geriatr Psychiatry 2020 28 64 71 10.1016/j.jagp.2019.03.023 31186157
J. Krell-Roesch J.A. Syrjanen M.M. Machulda et al. Neuropsychiatric symptoms and the outcome of cognitive trajectories in older adults free of dementia: The Mayo clinic study of aging Int J Geriatr Psychiatry 2021 36 1362 1369 10.1002/gps.5528 33724517 8451750
F. Panza M. Lozupone A. Bellomo B.P. Imbimbo Do anti-amyloid-β drugs affect neuropsychiatric status in Alzheimer’s disease patients? Ageing Res Rev 2019 55 1:CAS:528:DC%2BC1MXhvVOqtrnI 10.1016/j.arr.2019.100948 31454563
T. Mori H. Shimada H. Shinotoh et al. Apathy correlates with prefrontal amyloid β deposition in Alzheimer’s disease J Neurol Neurosurg Psychiatry 2014 85 449 455 10.1136/jnnp-2013-306110 24133289
D. Bensamoun R. Guignard A.J. Furst et al. Associations between neuropsychiatric symptoms and cerebral amyloid deposition in cognitively impaired elderly people J Alzheimers Dis 2016 49 387 398 1:CAS:528:DC%2BC2MXhvFKhsLfO 10.3233/JAD-150181 26484900
J. Krell-Roesch V.J. Lowe J. Neureiter et al. Depressive and anxiety symptoms and cortical amyloid deposition among cognitively normal elderly persons: the Mayo clinic study of aging Int Psychogeriatr 2018 30 245 251 10.1017/S1041610217002368 29198244
M. Brendel O. Pogarell G. Xiong et al. Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients Eur J Nucl Med Mol Imaging 2015 42 716 724 1:CAS:528:DC%2BC2MXitVOltbo%3D 10.1007/s00259-014-2975-4 25631614 5849231
M. Johansson E. Stomrud O. Lindberg et al. Apathy and anxiety are early markers of Alzheimer’s disease Neurobiol Aging 2020 85 74 82 1:CAS:528:DC%2BC1MXitFWlsb3O 10.1016/j.neurobiolaging.2019.10.008 31735378
F. Yasuno H. Kazui N. Morita et al. High amyloid-β deposition related to depressive symptoms in older individuals with normal cognition: a pilot study Int J Geriatr Psychiatry 2016 31 920 928 10.1002/gps.4409 26766490
Z. Ismail E.E. Smith Y. Geda et al. Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment Alzheimers Dementia 2016 12 195 202 10.1016/j.jalz.2015.05.017
Z. Ismail L. Agüera-Ortiz H. Brodaty et al. The mild behavioral impairment checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations J Alzheimers Dis 2017 56 929 938 10.3233/JAD-160979 28059789 5652315
F.Z. Lussier T.A. Pascoal M. Chamoun et al. Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals Alzheimers Dementia 2020 16 192 199 10.1002/alz.12007
N.S. Tommasi C. Gonzalez D. Briggs et al. Affective symptoms and regional cerebral tau burden in early-stage Alzheimer’s disease Int J Geriatr Psychiatry 2021 36 1050 1058 10.1002/gps.5530 33682933 8187284
G.M. Babulal C.M. Roe S.H. Stout et al. Depression is associated with tau and not amyloid positron emission tomography in cognitively normal adults J Alzheimers Dis 2021 74 4 1045 1055 10.3233/JAD-191078
F. Yasuno H. Minami H. Hattori for the Alzheimer’s Disease Neuroimaging Initiative Relationship between neuropsychiatric symptoms and Alzheimer’s disease pathology: an in vivo positron emission tomography study Int J Geriatr Psychiatry 2021 36 598 605 10.1002/gps.5459 33165946
C. Tissot J. Therriault T.A. Pascoal et al. Association between regional tau pathology and neuropsychiatric symptoms in aging and dementia due to Alzheimer’s disease Alzheimers Dementia Transl Res Clin Interv 2021 10.1002/trc2.12154
C.R. Jack D.S. Knopman W.J. Jagust et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers Lancet Neurol 2013 12 207 216 1:CAS:528:DC%2BC3sXhslCht7o%3D 10.1016/S1474-4422(12)70291-0 23332364 3622225
L. Rizzolo J. Narbutas M. Van Egroo et al. Relationship between brain AD biomarkers and episodic memory performance in healthy aging Brain Cogn 2021 148 10.1016/j.bandc.2020.105680 33418512
S. Mattis Dementia rating scale. Professional manual 1988 Odessa, FL Psychological Assessment Resources
M.F. Folstein S.E. Folstein P.R. McHugh Mini-mental state J Psychiatr Res 1975 12 189 198 1:STN:280:DyaE28%2FntFKjtw%3D%3D 10.1016/0022-3956(75)90026-6 1202204
A.T. Beck N. Epstein G. Brown R.A. Steer An inventory for measuring clinical anxiety: psychometric properties J Consult Clin Psychol 1988 56 893 897 1:STN:280:DyaL1M%2FnvF2mtg%3D%3D 10.1037/0022-006X.56.6.893 3204199
A.T. Beck R.A. Steer M.G. Carbin Psychometric properties of the Beck depression inventory: twenty-five years of evaluation Clin Psychol Rev 1988 8 77 100 10.1016/0272-7358(88)90050-5
C. Mouraux M. Van Egroo D. Chylinski et al. Effort during prolonged wakefulness is associated with performance to attentional and executive tasks but not with cortical excitability in late-middle-aged healthy individuals Neuropsychology 2023 37 77 92 10.1037/neu0000868 36355646
M. Sarazin V. Chauviré E. Gerardin et al. The amnestic syndrome of hippocampal type in Alzheimer’s disease: an MRI study JAD 2010 22 285 294 10.3233/JAD-2010-091150 20847406
G. Sánchez-Benavides B. Gómez-Ansón J.L. Molinuevo et al. Medial temporal lobe correlates of memory screening measures in normal aging, MCI, and AD J Geriatr Psychiatry Neurol 2010 23 100 108 10.1177/0891988709355271 20029056
J. Narbutas M. Van Egroo D. Chylinski et al. Associations between cognitive complaints, memory performance, mood, and amyloid-β accumulation in healthy amyloid negative late-midlife individuals J Alzheimers Dis 2021 83 127 141 1:CAS:528:DC%2BB3MXhvFWrsL7J 10.3233/JAD-210332 34275899
W.E. Klunk R.A. Koeppe J.C. Price et al. The Centiloid project: standardizing quantitative amyloid plaque estimation by PET Alzheimer’s Dementia 2015 11 1 15.e4 10.1016/j.jalz.2014.07.003 25443857
A. Ishiki R. Harada H. Kai et al. Neuroimaging-pathological correlations of [18F]THK5351 PET in progressive supranuclear palsy Acta Neuropathol Commun 2018 6 53 1:CAS:528:DC%2BC1MXisFKmtr8%3D 10.1186/s40478-018-0556-7 29958546 6025736
E.T. Rolls C.-C. Huang C.-P. Lin et al. Automated anatomical labelling atlas 3 Neuroimage 2020 206 10.1016/j.neuroimage.2019.116189 31521825
F.I.M. Craik T.A. Salthouse The handbook of aging and cognition 2011 3 New York Psychology Press 10.4324/9780203837665
D.M. Rentz E.C. Mormino K.V. Papp et al. Cognitive resilience in clinical and preclinical Alzheimer’s disease: the association of amyloid and tau burden on cognitive performance Brain Imaging Behav 2017 11 383 390 10.1007/s11682-016-9640-4 27738998 5391311
R. Ismail P. Parbo L.S. Madsen et al. The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study J Neuroinflammation 2020 17 151 1:CAS:528:DC%2BB3cXhtVyqtbfN 10.1186/s12974-020-01820-6 32375809 7203856
S.L. Leal S.N. Lockhart A. Maass et al. Subthreshold amyloid predicts tau deposition in aging J Neurosci 2018 38 4482 4489 1:CAS:528:DC%2BC1cXhvVemurzP 10.1523/JNEUROSCI.0485-18.2018 29686045 5943976
J. Narbutas D. Chylinski M. Van Egroo et al. 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 2021 10.3389/fnagi.2021.666181 34122044 8194490
R.A. Sperling E.C. Mormino A.P. Schultz et al. The impact of amyloid-beta and tau on prospective cognitive decline in older individuals Ann Neurol 2019 85 181 193 1:CAS:528:DC%2BC1MXhvFKjtrY%3D 10.1002/ana.25395 30549303 6402593
J. Dumurgier B.J. Hanseeuw F.B. Hatling et al. Alzheimer’s biomarkers and future decline in cognitive normal older adults J Alzheimers Dis 2017 60 1451 1459 1:CAS:528:DC%2BC2sXhsl2gtLbI 10.3233/JAD-170511 29036824 5773095
P. Carrillo-Mora R. Luna L. Colín-Barenque Amyloid beta: multiple mechanisms of toxicity and only some protective effects? Oxid Med Cell Longev 2014 2014 1:CAS:528:DC%2BC2cXhs12jsbfK 10.1155/2014/795375
M. Joannette C. Bocti P.S. Dupont et al. Education as a moderator of the relationship between episodic memory and amyloid load in normal aging J Gerontol Ser A 2020 75 1820 1826 1:CAS:528:DC%2BB3MXotFOntLs%3D 10.1093/gerona/glz235
L.C.P. Banning I.H.G.B. Ramakers S. Köhler et al. The association between biomarkers and neuropsychiatric symptoms across the Alzheimer’s disease spectrum Am J Geriatr Psychiatry 2020 28 735 744 10.1016/j.jagp.2020.01.012 32088096
M.E. Peters C.G. Lyketsos Beyond memory: a focus on the other neuropsychiatric symptoms of dementia Am J Geriatr Psychiatry 2015 23 115 118 10.1016/j.jagp.2014.11.002 25575934 4293074
J. Neureiter J. Krell-Roesch A. Pink et al. Amyloid-β, neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a prospective cohort study (S35.003) Neurology 2016 10.1212/WNL.86.16_supplement.S35.003
L. Apostolova N. Goukasian T. Do et al. Effect of brain amyloidosis on the emergence of neuropsychiatric behaviors in MCI over time (I12.012) Neurology 2016 86 Suppl 16 P2.232 10.1212/WNL.86.16_supplement.P2.232
N.F. Martínez I.E. Allen J. Kramer et al. Neuropsychiatric symptoms in early and late onset Alzheimer’s Disease (2452) Neurology 2021 10.1212/WNL.96.15_supplement.2452 34556567
N.A. Murugan K. Chiotis E. Rodriguez-Vieitez et al. Cross-interaction of tau PET tracers with monoamine oxidase B: evidence from in silico modelling and in vivo imaging Eur J Nucl Med Mol Imaging 2019 46 1369 1382 1:CAS:528:DC%2BC1MXntFKgsbg%3D 10.1007/s00259-019-04305-8 30919054 6486902
R. Harada A. Ishiki H. Kai et al. Correlations of 18F-THK5351 PET with postmortem burden of tau and astrogliosis in Alzheimer disease J Nucl Med 2018 59 671 674 1:CAS:528:DC%2BC1cXitlKgsbbM 10.2967/jnumed.117.197426 28864633
M. Van Egroo D. Chylinski J. Narbutas et al. Early brainstem [18F]THK5351 uptake is linked to cortical hyperexcitability in healthy aging JCI Insight 2021 6 10.1172/jci.insight.142514 33290274 7934880
M. D’Amelio P.M. Rossini Brain excitability and connectivity of neuronal assemblies in Alzheimer’s disease: from animal models to human findings Prog Neurobiol 2012 99 42 60 10.1016/j.pneurobio.2012.07.001 22789698
