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Challenges of multimorbidity of the aging brain: a critical update

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

A major problem in elderly patients is the high incidence of multiple pathologies, referred to as multimorbidity, in the aging brain. It has been increasingly recognized that co-occurrence of neurodegenerative proteinopathies and other pathologies including cerebrovascular disorders is a frequent event in the brains of both cognitively intact and impaired aged subjects. Although clinical and neuropathological diagnostic criteria of the major neurodegenerative diseases have been improved, major challenges arise from cerebral multimorbidity, and the thresholds to cause clinical overt dementia are ill defined. More than 80 % of aged human brains show neurodegenerative non-Alzheimer type proteinopathies and other pathologies which, however, frequently have been missed clinically and are even difficult to identify at neuropathological examination. Autopsy studies differ in selection criteria and the applied evaluation methods. Therefore, irrespective of the clinical symptoms, the frequency of cerebral pathologies vary considerably: Alzheimer-related pathology is seen in 19–100 %, with “pure” Alzheimer’s disease (AD) in 17–72 %, Lewy pathology in 6–39 % (AD + Lewy disease 9–28 %), vascular pathologies in 28–93 % (10.7–78 % “pure” vascular dementia), TDP-43 proteinopathy in 6–39 %, hippocampal sclerosis in 8–1 %, and mixed pathologies in 10–93 %. These data clearly suggest that pathologically deposited proteins in neurodegenerating diseases mutually interact and are influenced by other factors, in particular cardiovascular and cerebrovascular ones, to promote cognitive decline and other clinical symptoms. It is obvious that cognitive and other neuropsychiatric impairment in the aged result from a multimorbid condition in the CNS rather than from a single disease and that the number of complex pathologies progresses with increasing age. These facts have implications for improvement of the clinical diagnosis and prognosis, the development of specific biomarkers, preventive strategies and better treatment of cerebral multimorbidity.

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Abbreviations

AD:

Alzheimer’s disease

AGD:

Argyrophilic grain disease

Aβ:

β-Amyloid

αSyn:

α-Synuclein

CAA:

Cerebral amyloid angiopathy

CBD:

Corticobasal degeneration

CERAD:

Consortium to Establish a Registry for Alzheimer’s Disease

CN:

Cognitively normal

CVD:

Cerebrovascular disease

CVL:

Cerebrovascular lesion

DLB:

Dementia with Lewy bodies

FTLD:

Frontotemporal lobe degeneration

GCI:

Glial cytoplasmic inclusions

HS:

Hippocampal sclerosis

LB:

Lewy body

LBD:

Lewy body disease

MCI:

Mild cognitive impairment

MSA:

Multiple system atrophy

NACC:

National Alzheimer’s Coordinating Center

NFTs:

Neurofibrillary tangles

NIA:

National Institute on Aging

PSP:

Progressive supranuclear palsy

SVD:

Small vessel disease

TDP-43:

TAR DNA binding protein 43

VaD:

Vascular dementia

VCI/VaD:

Vascular cognitive impairment/vascular dementia

VCI:

Vascular cognitive impairment

VITA:

Vienna trans-danube aging study

WML:

White matter lesion

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Authors and Affiliations

  1. Institute of Clinical Neurobiology, Kenyongasse 18, 1070, Vienna, Austria

    Kurt A. Jellinger

  2. Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK

    Johannes Attems

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  1. Kurt A. Jellinger
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  2. Johannes Attems
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Correspondence to Kurt A. Jellinger.

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To the memory of our old friend, Prof. Siegfried Hoyer, who passed away after a long way as an excellent neuroscientist, in January 2014.

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Jellinger, K.A., Attems, J. Challenges of multimorbidity of the aging brain: a critical update. J Neural Transm 122, 505–521 (2015). https://doi.org/10.1007/s00702-014-1288-x

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