Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

Melina Stark1, Steffen Wolfsgruber2, Luca Kleineidam2

  • 1From 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.

Neurology
|October 11, 2023
PubMed
Abstract

Insights

Minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) indicate a higher risk for Alzheimer's disease (AD) progression. Assessing MNPD aids in predicting cognitive decline and stratifying risk in clinical trials.

Area of Science:

  • Neuroscience
  • Gerontology
  • Clinical Neurology

Background:

  • Subjective cognitive decline (SCD) is an early sign of cognitive impairment.
  • Minor neuropsychological deficits (MNPD) may indicate underlying neuropathology.
  • Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF) are crucial for diagnosis.

Purpose of the Study:

  • To investigate the association between MNPD in SCD patients and AD biomarkers.
  • To determine if MNPD predict cognitive decline and progression to mild cognitive impairment (MCI).
  • To assess the clinical utility of MNPD in risk stratification for AD.

Main Methods:

  • Longitudinal study of SCD patients and healthy controls (HC) with CSF and cognitive data.
  • MNPD defined as performance at least 0.5SD below the mean on neuropsychological tests.
  • Comparison of CSF AD biomarker levels, cognitive trajectories, and MCI progression risk between SCD groups with and without MNPD.

Main Results:

  • SCD patients with MNPD exhibited significantly more abnormal CSF AD biomarkers, faster cognitive decline, and a 4-fold increased risk of progression to MCI.
  • MNPD demonstrated a positive predictive value of 57% and negative predictive value of 86% for SCD to MCI progression within 3 years.
  • SCD patients without MNPD also showed increased cognitive decline and MCI risk compared to HC without MNPD.

Conclusions:

  • MNPD are a significant risk factor for AD-related clinical progression in individuals with SCD.
  • Assessing MNPD can improve individual risk prediction and AD clinical trial stratification.
  • SCD itself is a risk factor for cognitive decline, irrespective of MNPD presence.

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