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Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment and Alzheimer’s disease with dementia

Published online by Cambridge University Press:  17 August 2021

Nikias Siafarikas Open the ORCID record for Nikias Siafarikas [Opens in a new window] ,
Dag Alnæs ,
Jennifer Monereo-Sanchez ,
Martina J. Lund ,
Geir Selbaek ,
Maria Stylianou-Korsnes ,
Karin Persson ,
Maria Lage Barca ,
Ina Selseth Almdahl  and
Tormod Fladby
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Nikias Siafarikas*
Affiliation:
Department of Geriatric Psychiatry, Akershus University Hospital, Lørenskog, Norway
Dag Alnæs
Affiliation:
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway Bjørknes College, Oslo, Norway
Jennifer Monereo-Sanchez
Affiliation:
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
Martina J. Lund
Affiliation:
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
Geir Selbaek
Affiliation:
Norwegian National Advisory Unit on Aging and Health, Vestfold Hospital Trust, Tønsberg, Norway Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
Maria Stylianou-Korsnes
Affiliation:
Department of Old Age Psychiatry, Oslo University Hospital, Oslo, Norway Department of Psychology, University of Oslo, Oslo, Norway
Karin Persson
Affiliation:
Norwegian National Advisory Unit on Aging and Health, Vestfold Hospital Trust, Tønsberg, Norway Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
Maria Lage Barca
Affiliation:
Norwegian National Advisory Unit on Aging and Health, Vestfold Hospital Trust, Tønsberg, Norway Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
Ina Selseth Almdahl
Affiliation:
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway Department of Old Age Psychiatry, Oslo University Hospital, Oslo, Norway
Tormod Fladby
Affiliation:
Department of Neurology, Akershus University Hospital, Lørenskog, Norway Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway
Dag Aarsland
Affiliation:
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK Centre of Age-Related Medicine, University Hospital Stavanger, Stavanger, Norway
Ole A. Andreassen
Affiliation:
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway K.G. Jebsen Center for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway
Lars T. Westlye
Affiliation:
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway K.G. Jebsen Center for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway Department of Psychology, University of Oslo, Oslo, Norway
*
Correspondence should be addressed to: Nikias Siafarikas, Department for Old Age Psychiatry, Akershus University Hospital, Sykehusveien 25, 1474 Lørenskog, Norway. Telephone. 004796884452, Email: [email protected].
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Summary

We present associations between neuropsychiatric symptoms (NPS) and brain morphology in a large sample of patients with mild cognitive impairment (MCI) and Alzheimer’s disease with dementia (AD dementia).

Several studies assessed NPS factor structure in MCI and AD dementia, but we know of no study that tested for associations between NPS factors and brain morphology. The use of factor scores increases parsimony and power. For transparency, we performed an additional analysis with selected Neuropsychiatric Inventory – Questionnaire (NPI-Q) items. Including regional cortical thickness, cortical and subcortical volumes, we examined associations between NPS and brain morphology across the whole brain in an unbiased fashion. We reported both statistical significance and effect sizes, using linear models adjusted for multiple comparisons by false discovery rate (FDR). Moreover, we included an interaction term for diagnosis and could thereby compare associations of NPS and brain morphology between MCI and AD dementia.

We found an association between the factor elation and thicker right anterior cingulate cortex across MCI and AD dementia. Associations between the factors depression to thickness of the banks of the left superior temporal sulcus and psychosis to the left post-central volume depended on diagnosis: in MCI these associations were positive, in AD dementia negative.

Our findings indicate that NPS in MCI and AD dementia are not exclusively associated with atrophy and support previous findings of associations between NPS and mainly frontotemporal brain structures.

Keywords

neuroimagingmild cognitive impairmentAlzheimer’s diseasedementianeuropsychiatric symptomsprincipal component analysis
Type
Original Research Article
Information
International Psychogeriatrics , Volume 33 , Special Issue 11: Issue Theme: Advances in Assessment and Diagnosis of Dementia , November 2021 , pp. 1217 - 1228
Copyright
© International Psychogeriatric Association 2021

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References

Alves, G. S., et al. (2017). Neuroimaging findings related to behavioral disturbances in Alzheimer’s disease: a systematic review. Current Alzheimer Research, 14, 61–75.CrossRefGoogle ScholarPubMed
Apostolova, L. G., et al. (2007). Structural correlates of apathy in Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders, 24, 91–97.CrossRefGoogle ScholarPubMed
Auning, E., et al. (2015). Neurobiological correlates of depressive symptoms in people with subjective and mild cognitive impairment. Acta Psychiatrica Scandinavica, 131, 139–147.CrossRefGoogle ScholarPubMed
Bakkane Bendixen, A., Hartberg, C. B., Selbaek, G. and Engedal, K. (2016). Symptoms of anxiety in older adults with depression, dementia, or psychosis: a principal component analysis of the geriatric anxiety inventory. Dementia and Geriatric Cognitive Disorders, 42, 310–322.CrossRefGoogle ScholarPubMed
Balthazar, M. L., et al. (2014). Neuropsychiatric symptoms in Alzheimer’s disease are related to functional connectivity alterations in the salience network. Human Brain Mapping, 35, 1237–1246.CrossRefGoogle ScholarPubMed
Bendixen, A. B. and Engedal, K. (2016). Anxiety among older psychiatric patients: a hidden comorbidity? Aging and Mental Health, 20, 1131–1138.CrossRefGoogle ScholarPubMed
Benjamini, Y. and Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. Series B (Methodological), 57, 289.CrossRefGoogle Scholar
Berthoz, S., Blair, R. J. R., Le Clec’h, G. and Martinot, J. L. (2002). Emotions: from neuropsychology to functional imaging. International Journal of Psychology, 37, 193–203.CrossRefGoogle Scholar
Boublay, N., Schott, A. M. and Krolak-Salmon, P. (2016). Neuroimaging correlates of neuropsychiatric symptoms in Alzheimer’s disease: a review of 20 years of research. European Journal of Neurology, 23, 1500–1509.CrossRefGoogle ScholarPubMed
Buckner, R. L., et al. (2005). Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. The Journal of Neuroscience, 25, 7709–7717.CrossRefGoogle ScholarPubMed
Cipriani, G., Lucetti, C., Nuti, A. and Danti, S. (2014). Wandering and dementia. Psychogeriatrics, 14, 135–142.CrossRefGoogle ScholarPubMed
Cordova-Palomera, A., et al. (2017). Disrupted global metastability and static and dynamic brain connectivity across individuals in the Alzheimer’s disease continuum. Scientific Reports, 7, 40268.CrossRefGoogle ScholarPubMed
Cullen, K. R., et al. (2009). A preliminary study of functional connectivity in comorbid adolescent depression. Neuroscience Letters, 460, 227–231.CrossRefGoogle ScholarPubMed
Cummings, J. L., et al. (1994). The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44, 2308–2314.CrossRefGoogle ScholarPubMed
Dale, A. M., Fischl, B. and Sereno, M. I. 1999. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage, 9, 179–194.CrossRefGoogle ScholarPubMed
Dhikav, V., Sethi, M. and Anand, K. S. 2014. Medial temporal lobe atrophy in Alzheimer’s disease/mild cognitive impairment with depression. British Journal of Radiology, 87, 20140150.CrossRefGoogle ScholarPubMed
Enache, D., et al. 2015. Medial temporal lobe atrophy and depressive symptoms in elderly patients with and without Alzheimer disease. Journal of Geriatric Psychiatry and Neurology, 28, 40–48.CrossRefGoogle ScholarPubMed
Engedal, K., Haugen, P., Gilje, K. and Laake, P. (1988). Efficacy of short mental tests in the detection of mental impairment in old age. Comprehensive gerontology. Section A, Clinical and Laboratory Sciences, 2, 87–93.Google ScholarPubMed
Fischl, B. (2012). FreeSurfer. Neuroimage, 62, 774–781.CrossRefGoogle ScholarPubMed
Fischl, B. and Dale, A. M. (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences of the USA, 97, 11050–11055.CrossRefGoogle ScholarPubMed
Fjell, A. M., McEvoy, L., Holland, D., Dale, A. M. and Walhovd, K. B. (2014). What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Progress in Neurobiology, 117, 20–40.CrossRefGoogle ScholarPubMed
Folstein, M. F., Folstein, S. E. and McHugh, P. R. 1975. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.CrossRefGoogle ScholarPubMed
Frangou, S., et al. (2021). Cortical thickness across the lifespan: data from 17,075 healthy individuals aged 3-90 years. Human Brain Mapping. doi: 10.1002/hbm.25364. Online ahead of print.CrossRefGoogle Scholar
García-Martí, G., et al. (2008). Schizophrenia with auditory hallucinations: a voxel-based morphometry study. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32, 72–80.CrossRefGoogle ScholarPubMed
Geda, Y. E., et al. (2013). Neuropsychiatric symptoms in Alzheimer’s disease: past progress and anticipation of the future. Alzheimer’s and Dementia, 9, 602–608.CrossRefGoogle Scholar
Ghazi-Saidi, L., Walsh, R. R., Shan, G. and Banks, S. J. (2018). Biomarkers of cognitive impairment: brain cortical thickness, volumetrics, and cerebrospinal fluid. Alzheimer Disease & Associated Disorders, 32, 255–257.CrossRefGoogle ScholarPubMed
Guercio, B. J., et al. (2015). Apathy is associated with lower inferior temporal cortical thickness in mild cognitive impairment and normal elderly individuals. The Journal of Neuropsychiatry and Clinical Neurosciences, 27, e22–e27.CrossRefGoogle ScholarPubMed
Hashimoto, H., et al. 2006. Anxiety and regional cortical glucose metabolism in patients with Alzheimer’s disease. The Journal of Neuropsychiatry and Clinical Neurosciences, 18, 521–528.CrossRefGoogle ScholarPubMed
Hogstrom, L. J., Westlye, L. T., Walhovd, K. B. and Fjell, A. M. (2013). The structure of the cerebral cortex across adult life: age-related patterns of surface area, thickness, and gyrification. Cerebral Cortex, 23, 2521–2630.CrossRefGoogle ScholarPubMed
Howanitz, E., Bajulaiye, R. and Losonczy, M. (1995). Magnetic resonance imaging correlates of psychosis in Alzheimer’s disease. The Journal of Nervous and Mental Disease, 183, 548–549.CrossRefGoogle ScholarPubMed
Ismail, Z., Nguyen, M. Q., Fischer, C. E., Schweizer, T. A. and Mulsant, B. H. (2012). Neuroimaging of delusions in Alzheimer’s disease. Psychiatry Research, 202, 89–95.CrossRefGoogle ScholarPubMed
Kaufer, D. I., et al. (2000). Validation of the NPI-Q, a brief clinical form of the neuropsychiatric inventory. Journal of Neuropsychiatry and Clinical Neurosciences, 12, 233–239.CrossRefGoogle ScholarPubMed
Kotrla, K. J., Chacko, R. C., Harper, R. G., Jhingran, S. and Doody, R. (1995). SPECT findings on psychosis in Alzheimer’s disease. American Journal of Psychiatry, 152, 1470–1475.Google ScholarPubMed
Kristiansen, K. M. and Engedal, K. (2013). New quality registry in geriatric psychiatry. Tidsskr Nor Laegeforen, 133, 737–738.CrossRefGoogle ScholarPubMed
Kropf, E., Syan, S. K., Minuzzi, L. and Frey, B. N. (2019). From anatomy to function: the role of the somatosensory cortex in emotional regulation. Brazilian Journal of Psychiatry, 41, 261–269.CrossRefGoogle ScholarPubMed
Lebedeva, A., et al. (2014). Structural brain changes associated with depressive symptoms in the elderly with Alzheimer’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 85, 930–935.CrossRefGoogle ScholarPubMed
M, F. M., Molano, A., Castro, J. and Zarranz, J. J. (2010). Prevalence of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer’s disease, and its relationship with cognitive impairment. Current Alzheimer Research, 7, 517–526.Google ScholarPubMed
Maresova, P., Hruska, J., Klimova, B., Barakovic, S. and Krejcar, O. (2020). Activities of daily living and associated costs in the most widespread neurodegenerative diseases: a systematic review. Clinical Interventions in Aging, 15, 1841–1862.CrossRefGoogle ScholarPubMed
Milham, M. P., Craddock, R. C. and Klein, A. (2017). Clinically useful brain imaging for neuropsychiatry: how can we get there? Depression and Anxiety, 34, 578–587.CrossRefGoogle Scholar
Nakaaki, S., et al. (2013). Neuroanatomical abnormalities before onset of delusions in patients with Alzheimer’s disease: a voxel-based morphometry study. Neuropsychiatric Disease and Treatment, 9, 1–8.Google ScholarPubMed
Nowrangi, M. A., et al. (2021). The association of neuropsychiatric symptoms with regional brain volumes from patients in a tertiary multi-disciplinary memory clinic. International Psychogeriatrics, 33, 233–244.CrossRefGoogle Scholar
R CORE TEAM. (2017). R: A Language and Environment for Statistical Computing [Online]. Vienna, Austria: R Foundation for Statistical Computing. https://www.R-project.org/.Google Scholar
Rogne, H. B. G. and Ulstein, I. (2012). Validering av den norske kortversjonen av nevropsykiatrisk intervjuguide: NPI-Q en pilotstudie. Nordic Journal of Nursing Research, 32, 37–40.CrossRefGoogle Scholar
Rosenberg, P. B., Nowrangi, M. A. and Lyketsos, C. G. (2015). Neuropsychiatric symptoms in Alzheimer’s disease: what might be associated brain circuits? Molecular Aspects of Medicine, 43–44, 25–37.CrossRefGoogle ScholarPubMed
Salat, D. H., et al. (2004). Thinning of the cerebral cortex in aging. Cerebral Cortex, 14, 721–30.CrossRefGoogle Scholar
Serra, L., et al. (2010). Are the behavioral symptoms of Alzheimer’s disease directly associated with neurodegeneration? Journal of Alzheimer's Disease, 21, 627–639.CrossRefGoogle ScholarPubMed
Siafarikas, N., et al. (2018). Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer’s disease. International Psychogeriatrics, 30, 103–113.CrossRefGoogle ScholarPubMed
Starkstein, S. E., et al. (2009). Neuroimaging correlates of apathy and depression in Alzheimer’s disease. Journal of Neuropsychiatry and Clinical Neurosciences, 21, 259–265.CrossRefGoogle ScholarPubMed
Stella, F., et al. (2014). Neurobiological correlates of apathy in Alzheimer’s disease and mild cognitive impairment: a critical review. Journal of Alzheimer’s Disease, 39, 633–648.CrossRefGoogle ScholarPubMed
Stevens, F. L., Hurley, R. A. and Taber, K. H. (2011). Anterior cingulate cortex: unique role in cognition and emotion. Journal of Neuropsychiatry and Clinical Neurosciences, 23, 121–125.CrossRefGoogle ScholarPubMed
Takahashi, T., et al. (2010). An MRI study of the superior temporal subregions in patients with current and past major depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 34, 98–103.CrossRefGoogle ScholarPubMed
Trzepacz, P. T., et al. (2013). Frontolimbic atrophy is associated with agitation and aggression in mild cognitive impairment and Alzheimer’s disease. Alzheimer’s and Dementia, 9, S95–S104.e1.CrossRefGoogle ScholarPubMed
Udo De Haes, J. I., Maguire, R. P., Jager, P. L., Paans, A. M. and Den Boer, J. A. (2007). Methylphenidate-induced activation of the anterior cingulate but not the striatum: a [15O]H2O PET study in healthy volunteers. Human Brain Mapping, 28, 625–635.CrossRefGoogle ScholarPubMed
Van der Linde, R. M., Dening, T., Matthews, F. E. and Brayne, C. (2014). Grouping of behavioural and psychological symptoms of dementia. International Journal of Geriatric Psychiatry, 29, 562–568.CrossRefGoogle ScholarPubMed
Westlye, E. T., Lundervold, A., Rootwelt, H., Lundervold, A. J. and Westlye, L. T. (2011). Increased hippocampal default mode synchronization during rest in middle-aged and elderly APOE ϵ4 carriers: relationships with memory performance. Journal of Neuroscience, 31, 7775–7783.CrossRefGoogle Scholar
Westlye, L. T., et al. (2009). Increased sensitivity to effects of normal aging and Alzheimer’s disease on cortical thickness by adjustment for local variability in gray/white contrast: a multi-sample MRI study. Neuroimage, 47, 1545–1557.CrossRefGoogle ScholarPubMed
Westlye, L. T., et al. (2010). Differentiating maturational and aging-related changes of the cerebral cortex by use of thickness and signal intensity. Neuroimage, 52, 172–185.CrossRefGoogle ScholarPubMed
Whitehead, D., et al. (2012). Frontotemporal atrophy associated with paranoid delusions in women with Alzheimer’s disease. International Psychogeriatrics, 24, 99–107.CrossRefGoogle ScholarPubMed
Victoroff, J., et al. (2018). Noncognitive behavioral changes associated with Alzheimer’s disease: implications of neuroimaging findings. The Journal of Neuropsychiatry and Clinical Neurosciences, 30, 14–21.CrossRefGoogle ScholarPubMed
Winblad, B., et al. (2004). Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine, 256, 240–246.CrossRefGoogle Scholar
Wood, S. N. (2017). Generalized additive models: an introduction with R. Boca Raton: CRC Press/Taylor & Francis Group.CrossRefGoogle Scholar
World Health Organization. (1992). The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: WHO.Google Scholar
Zahodne, L. B., Gongvatana, A., Cohen, R. A., Ott, B. R. and Tremont, G. (2013). Are apathy and depression independently associated with longitudinal trajectories of cortical atrophy in mild cognitive impairment? The American Journal of Geriatric Psychiatry, 21, 1098–1106.CrossRefGoogle ScholarPubMed
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