Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

Melina Stark; Steffen Wolfsgruber; Luca Kleineidam; Ingo Frommann; Slawek Altenstein; Claudia Bartels; Frederic Brosseron; Katharina Buerger; Lena Burow; Michaela Butryn; Michael Ewers; Klaus Fliessbach; Tatjana Gabelin; Wenzel Glanz; Doreen Goerss; Daria Gref; Niels Hansen; Michael T Heneka; Petra Hinderer; Enise I Incesoy; Daniel Janowitz; Ingo Kilimann; Okka Kimmich; Christoph Laske; Matthias H Munk; Robert Perneczky; Oliver Peters; Lukas Preis; Josef Priller; Boris-Stephan Rauchmann; Ayda Rostamzadeh; Nina Roy-Kluth; Carolin Sanzenbacher; Anja Schneider; Björn H Schott; Annika Spottke; Eike Jakob Spruth; Stefan Teipel; Ina R Vogt; Jens Wiltfang; Emrah Duzel; Frank Jessen; Michael Wagner

doi:10.1212/WNL.0000000000207844

Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

Neurology. 2023 Nov 21;101(21):e2185-e2196. doi: 10.1212/WNL.0000000000207844. Epub 2023 Oct 11.

Authors

Melina Stark¹, Steffen Wolfsgruber², Luca Kleineidam², Ingo Frommann², Slawek Altenstein², Claudia Bartels², Frederic Brosseron², Katharina Buerger², Lena Burow², Michaela Butryn², Michael Ewers², Klaus Fliessbach², Tatjana Gabelin², Wenzel Glanz², Doreen Goerss², Daria Gref², Niels Hansen², Michael T Heneka², Petra Hinderer², Enise I Incesoy², Daniel Janowitz², Ingo Kilimann², Okka Kimmich², Christoph Laske², Matthias H Munk², Robert Perneczky², Oliver Peters², Lukas Preis², Josef Priller², Boris-Stephan Rauchmann², Ayda Rostamzadeh², Nina Roy-Kluth², Carolin Sanzenbacher², Anja Schneider², Björn H Schott², Annika Spottke², Eike Jakob Spruth², Stefan Teipel², Ina R Vogt², Jens Wiltfang², Emrah Duzel², Frank Jessen², Michael Wagner²

Affiliations

¹ From the German Center for Neurodegenerative Diseases (DZNE) (M.S., S.W., L.K., I.F., F.B., K.F., O.K., N.R.-K., A. Schneider, A. Spottke, I.R.V., F.J., M.W.), Bonn; Department of Neurodegenerative Diseases and Geriatric Psychiatry (M.S., S.W., L.K., I.F., K.F., A. Schneider, M.W.), University of Bonn Medical Center, Germany; German Center for Neurodegenerative Diseases (DZNE) (S.A., O.P., J.P., E.J.S.), Berlin; Department of Psychiatry and Psychotherapy (S.A., J.P., E.J.S.), Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Germany; Department of Psychiatry and Psychotherapy (C.B., N.H., B.H.S., J.W.), University Medical Center Goettingen, University of Goettingen, Germany; German Center for Neurodegenerative Diseases (DZNE) (K.B., M.E., R.P.), Munich; Institute for Stroke and Dementia Research (ISD) (K.B., M.E., D.J.), University Hospital, LMU Munich; Department of Psychiatry and Psychotherapy (L.B., R.P., B.-S.R.), University Hospital, LMU Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) (M.B., W.G., E.I.I., E.D.), Magdeburg; Department of Psychiatry and Psychotherapy (T.G., D. Gref, O.P., L.P.), Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) (D. Goerss, I.K., S.T.), Rostock; Department of Psychosomatic Medicine (D. Goerss, I.K., S.T.), Rostock University Medical Center, Germany; Luxembourg Center for Systems Biomedicine (LCSB) (M.T.H.), University of Luxembourg, Esch-sur-Alzette; German Center for Neurodegenerative Diseases (DZNE) (P.H., C.L., M.H.M., C.S.), Tübingen; Institute for Cognitive Neurology and Dementia Research (IKND) (E.I.I., E.D.), Otto-von-Guericke University, Magdeburg, Germany; Department for Psychiatry and Psychotherapy (E.I.I.), University Clinic Magdeburg, Germany; Section for Dementia Research (C.L.), Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Germany; Department of Psychiatry and Psychotherapy (M.H.M.), University of Tübingen, Germany; Munich Cluster for Systems Neurology (SyNergy) (R.P.), Germany; Ageing Epidemiology Research Unit (AGE) (R.P.), School of Public Health, Imperial College London, United Kingdom; Department of Psychiatry and Psychotherapy (J.P.), School of Medicine, Technical University of Munich, Germany; University of Edinburgh and UK DRI (J.P.), United Kingdom; Department of Neuroradiology (B.-S.R.), University Hospital, LMU Munich, Germany; Sheffield Institute for Translational Neuroscience (SITraN) (B.-S.R.), University of Sheffield, United Kingdom; Department of Psychiatry (A.R., F.J.), Medical Faculty, University of Cologne, Germany; German Center for Neurodegenerative Diseases (DZNE) (B.H.S., J.W.), Goettingen; Department of Neurology (A. Spottke), University of Bonn Medical Center, Germany; Neurosciences and Signaling Group (J.W.), Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Portugal; and Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (F.J.), University of Cologne, Germany. melina.stark@dzne.de.
² From the German Center for Neurodegenerative Diseases (DZNE) (M.S., S.W., L.K., I.F., F.B., K.F., O.K., N.R.-K., A. Schneider, A. Spottke, I.R.V., F.J., M.W.), Bonn; Department of Neurodegenerative Diseases and Geriatric Psychiatry (M.S., S.W., L.K., I.F., K.F., A. Schneider, M.W.), University of Bonn Medical Center, Germany; German Center for Neurodegenerative Diseases (DZNE) (S.A., O.P., J.P., E.J.S.), Berlin; Department of Psychiatry and Psychotherapy (S.A., J.P., E.J.S.), Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Germany; Department of Psychiatry and Psychotherapy (C.B., N.H., B.H.S., J.W.), University Medical Center Goettingen, University of Goettingen, Germany; German Center for Neurodegenerative Diseases (DZNE) (K.B., M.E., R.P.), Munich; Institute for Stroke and Dementia Research (ISD) (K.B., M.E., D.J.), University Hospital, LMU Munich; Department of Psychiatry and Psychotherapy (L.B., R.P., B.-S.R.), University Hospital, LMU Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) (M.B., W.G., E.I.I., E.D.), Magdeburg; Department of Psychiatry and Psychotherapy (T.G., D. Gref, O.P., L.P.), Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) (D. Goerss, I.K., S.T.), Rostock; Department of Psychosomatic Medicine (D. Goerss, I.K., S.T.), Rostock University Medical Center, Germany; Luxembourg Center for Systems Biomedicine (LCSB) (M.T.H.), University of Luxembourg, Esch-sur-Alzette; German Center for Neurodegenerative Diseases (DZNE) (P.H., C.L., M.H.M., C.S.), Tübingen; Institute for Cognitive Neurology and Dementia Research (IKND) (E.I.I., E.D.), Otto-von-Guericke University, Magdeburg, Germany; Department for Psychiatry and Psychotherapy (E.I.I.), University Clinic Magdeburg, Germany; Section for Dementia Research (C.L.), Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Germany; Department of Psychiatry and Psychotherapy (M.H.M.), University of Tübingen, Germany; Munich Cluster for Systems Neurology (SyNergy) (R.P.), Germany; Ageing Epidemiology Research Unit (AGE) (R.P.), School of Public Health, Imperial College London, United Kingdom; Department of Psychiatry and Psychotherapy (J.P.), School of Medicine, Technical University of Munich, Germany; University of Edinburgh and UK DRI (J.P.), United Kingdom; Department of Neuroradiology (B.-S.R.), University Hospital, LMU Munich, Germany; Sheffield Institute for Translational Neuroscience (SITraN) (B.-S.R.), University of Sheffield, United Kingdom; Department of Psychiatry (A.R., F.J.), Medical Faculty, University of Cologne, Germany; German Center for Neurodegenerative Diseases (DZNE) (B.H.S., J.W.), Goettingen; Department of Neurology (A. Spottke), University of Bonn Medical Center, Germany; Neurosciences and Signaling Group (J.W.), Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Portugal; and Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (F.J.), University of Cologne, Germany.

Abstract

Background and objectives: To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI).

Methods: This study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-β (Aβ)42/Aβ40, phosphorylated tau (p-tau₁₈₁)_, total tau and Aβ42/p-tau₁₈₁ levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M ± SD: 40.6 ± 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD.

Results: In our sample (N = 672, mean age: 70.7 ± 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46-6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5-75.4) and a negative predictive value of 86.0% (95% CI 81.9-90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215; HR: 4.09, 95% CI 2.07-8.09), while AD biomarker levels did not differ significantly between these groups.

Discussion: Our results suggest that MNPD are a risk factor for AD-related clinical progression in cognitively normal patients seeking medical counseling because of SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD.

Publication types

Observational Study

MeSH terms

Aged
Alzheimer Disease* / psychology
Amyloid beta-Peptides
Biomarkers
Cognitive Dysfunction* / psychology
Disease Progression
Female
Humans
Longitudinal Studies
Male
Middle Aged
tau Proteins

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins