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Staging Neurodegenerative Disorders: Structural, Regional, Biomarker, and Functional Progressions

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Abstract

The notion of staging in the neurodegenerative disorders is modulated by the constant and progressive loss of several aspects of brain structural integrity, circuitry, and neuronal processes. These destructive processes eventually remove individuals’ abilities to perform at sufficient and necessary functional capacity at several levels of disease severity. The classification of (a) patients on the basis of diagnosis, risk prognosis, and intervention outcome, forms the basis of clinical staging, and (b) laboratory animals on the basis of animal model of brain disorder, extent of insult, and dysfunctional expression, provides the components for the clinical staging and preclinical staging , respectively, expressing associated epidemiological, biological, and genetic characteristics. The major focus of clinical staging in the present account stems from the fundamental notions of Braak staging as they describe the course and eventual prognosis for Alzheimer’s disease, Lewy Body dementia, and Parkinson’s disease. Mild cognitive impairment, which expresses the decline in episodic and semantic memory performance below the age-adjusted normal range without marked loss of global cognition or activities of daily living, and the applications of longitudinal magnetic resonance imaging, major instruments for the monitoring of either disease progression in dementia, present important challenges for staging concepts. Although Braak notions present the essential basis for further developments, current staging conceptualizations seem inadequate to comply with the massive influx of information dealing with neurodegenerative processes in brain, advanced both under clinical realities, and discoveries in the laboratory setting. The contributions of various biomarkers of disease progression, e.g., amyloid precursor protein, and neurotransmitter system imbalances, e.g., dopamine receptor supersensitivity and interactive propensities, await their incorporation into the existing staging models thereby underlining the ongoing, dynamic feature of the staging of brain disorders.

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Abbreviations

AD:

Alzheimer disease

APP:

Amyloid precursor protein

AS:

α-Synucleinopathy

CBD:

Corticobasal degeneration

CBS:

Corticobasal syndrome

CIT:

2-β-Carboxymethoxy-3-β-(4-iodophenyl) tropane

CSF:

Cerebrospinal fluid

DA:

Dopamine

DARSS:

Dopamine receptor supersensitivity

DG-PET:

Deoxyglucose-positron emission tomography

fMRI:

Functional magnetic resonance imaging

FTD:

Frontotemporal dementia

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

HNPCs:

Human neural progenitor cells

LB:

Lewy body

LBD:

Dementia with Lewy bodies

MCI:

Mild cognitive impairment

NFT:

Neurofibrillary tangle

PD:

Parkinson’s disease

PDD:

Parkinson’s disease dementia

PDRP:

Parkinson disease motor-related pattern

PET:

Positron emission tomography

PiB:

Pittsburgh compound B

RSS:

Receptor supersensitivity

SMI:

Subjective memory impairment

SN:

Substantia nigra

SPECT:

Single photon emission computerized tomography

SPECT:

99m Tc-HMPAO, 500 M Bq Techmetium-99 m hexamethylpropylene amine oxime

VBM:

Voxel based morphometry

VZV:

Varicella Zoster virus

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Authors and Affiliations

  1. Department of Psychology, University of Gothenburg, Box 500, SE-405 30, Gothenburg, Sweden

    Trevor Archer

  2. Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA

    Richard M. Kostrzewa

  3. Departments of Psychology and Psychiatry, Queen’s University, Kingston, Ontario, K7L 3N6, Canada

    Richard J. Beninger

  4. Servicio Psiquitrico, Hospital Universitario 12 de Octobre, 28041, Madrid, Spain

    Tomas Palomo

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  1. Trevor Archer
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  2. Richard M. Kostrzewa
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  3. Richard J. Beninger
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  4. Tomas Palomo
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Correspondence to Trevor Archer.

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Archer, T., Kostrzewa, R.M., Beninger, R.J. et al. Staging Neurodegenerative Disorders: Structural, Regional, Biomarker, and Functional Progressions. Neurotox Res 19, 211–234 (2011). https://doi.org/10.1007/s12640-010-9190-2

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  • DOI: https://doi.org/10.1007/s12640-010-9190-2

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