Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline.

Neurology

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.

Published: November 2023

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 study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the 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-tau) total tau and Aβ42/p-tau levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up ± : 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663030	PMC
http://dx.doi.org/10.1212/WNL.0000000000207844	DOI Listing

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