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Mapping the neuroanatomy of functional decline in Alzheimer’s disease from basic to advanced activities of daily living

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Abstract

Background

Impairments in activities of daily living (ADL) are a criterion for Alzheimer’s disease (AD) dementia. However, ADL gradually decline in AD, impacting on advanced (a-ADL, complex interpersonal or social functioning), instrumental (IADL, maintaining life in community), and finally basic functions (BADL, activities related to physiological and self-maintenance needs). Information and communication technologies (ICT) have become an increasingly important aspect of daily functioning. Yet, the links of ADL, ICT, and neuropathology of AD dementia are poorly understood. Such knowledge is critical as it can provide biomarker evidence of functional decline in AD.

Methods

ADL were evaluated with the Technology–Activities of Daily Living Questionnaire (T-ADLQ) in 33 patients with AD and 30 controls. ADL were divided in BADL, IADL, and a-ADL. The three domain subscores were covaried against gray matter atrophy via voxel-based morphometry.

Results

Our results showed that three domain subscores of ADL correlate with several brain structures, with a varying degree of overlap between them. BADL score correlated mostly with frontal atrophy, IADL with more widespread frontal, temporal and occipital atrophy and a-ADL with occipital and temporal atrophy. Finally, ICT subscale was associated with atrophy in the precuneus.

Conclusions

The association between ADL domains and neurodegeneration in AD follows a traceable neuropathological pathway which involves different neural networks. This the first evidence of ADL phenotypes in AD characterised by specific patterns of functional decline and well-defined neuropathological changes. The identification of such phenotypes can yield functional biomarkers for dementias such as AD.

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Acknowledgements

Funding from CONICYT/FONDECYT/11404223 (to A.S, C.D, E.B, F.H, C.M., and P.B); FONDAP Program Grant 15150012 (to AS, PL, GF and AI); CONICYT/FONDECYT (Regular 1170010), CONICYT/FONDECYT regular 1160940 (to AS and PL), the INECO Foundation (to AI), the Global Brain Health Institute (GBHI-UCSF) (to AI),  the Inter-American Development Bank (IADB) (to AI and AS), PIA-CONICYT Basal Funds for Centers of Excellence Project FB0003 (to A.S; PB and FH) and the Alzheimer’s Society (Grant AS-SF-14-008) (to MAP).

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Authors and Affiliations

  1. Geroscience Center for Brain Health and Metabolism (GERO), Faculty of Medicine, University of Chile, Avenida Salvador 486, Providencia, Santiago, Chile

    Andrea Slachevsky, Gonzalo Forno, Patricia Lillo & Fernando Henriquez

  2. Neuropsychology and Clinical Neuroscience Laboratory (LANNEC), Physiopathology Department - ICBM, Neurocience and East Neuroscience Departments, Faculty of Medicine, University of Chile, Avenida Salvador 486, Providencia, Santiago, Chile

    Andrea Slachevsky, Gonzalo Forno & Fernando Henriquez

  3. Memory and Neuropsychiatric Clinic (CMYN) Neurology Department, Hospital del Salvador and Faculty of Medicine, University of Chile, Av. Salvador 364, Providencia, Santiago, Chile

    Andrea Slachevsky, Gonzalo Forno, Fernando Henriquez & Carlos Muñoz-Neira

  4. Center for Advanced Research in Education (CIAE), University of Chile, 8330014, Santiago, Chile

    Paulo Barraza & Fernando Henriquez

  5. Servicio de Neurología, Departamento de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile

    Andrea Slachevsky

  6. School of Health Sciences, University of East Anglia, Norwich, UK

    Eneida Mioshi & Michael Hornberger

  7. Neurology and Neurosurgery Department, Clinical Hospital, University of Chile, Santiago, Chile

    Carolina Delgado

  8. Neuroradiologic Department, Institute of Neurosurgery Asenjo, Santiago, Chile

    Eduardo Bravo & Mauricio Farias

  9. Psychology Department, School of Psychological Sciences & Health, University of Strathclyde, Glasgow, UK

    Mario A. Parra

  10. Universidad Autonoma del Caribe, Barranquilla, Colombia

    Agustin Ibañez & Mario A. Parra

  11. Institute of Cognitive and Translational Neuroscience (INCYT), INECO Foundation, Favaloro University, Buenos Aires, Argentina

    Agustin Ibañez

  12. National Scientific and Technical Research Council (CONICET), Av. Rivadavia 1917, C1033AAJ, Buenos Aires, Argentina

    Agustin Ibañez

  13. Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibañez, Diagonal Las Torres 2640, Santiago, Chile

    Agustin Ibañez

  14. Centre of Excellence in Cognition and its Disorders, Australian Research Council (ACR), Sydney, Australia

    Agustin Ibañez

  15. Norfolk and Suffolk Foundation Trust, Norwich, UK

    Michael Hornberger

  16. Departamento de Neurociencia y Neurología Sur, Facultad de Medicina, Universidad de Chile, Santiago, Chile

    Patricia Lillo

  17. Departamento de Neurociencia, Facultad de Medicina, Universidad de Chile, Santiago, Chile

    Andrea Slachevsky, Carolina Delgado & Patricia Lillo

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  1. Andrea Slachevsky
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  2. Gonzalo Forno
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  3. Paulo Barraza
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  10. Carlos Muñoz-Neira
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Correspondence to Andrea Slachevsky.

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All the procedures conducted with the participants of this study were carried out according to the Declaration of Helsinki. Ethical approvals were provided by the Ethical and Scientific Committees of the East Metropolitan Health Service and Hospital Clínico Universidad de Chile from Santiago, Chile.

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Slachevsky, A., Forno, G., Barraza, P. et al. Mapping the neuroanatomy of functional decline in Alzheimer’s disease from basic to advanced activities of daily living. J Neurol 266, 1310–1322 (2019). https://doi.org/10.1007/s00415-019-09260-w

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