At the interface of sensory and motor dysfunctions and Alzheimer's disease

Mark W Albers¹, Grover C Gilmore², Jeffrey Kaye³, Claire Murphy⁴, Arthur Wingfield⁵, David A Bennett⁶, Adam L Boxer⁷, Aron S Buchman⁶, Karen J Cruickshanks⁸, Davangere P Devanand⁹, Charles J Duffy¹⁰, Christine M Gall¹¹, George A Gates¹², Ann-Charlotte Granholm¹³, Takao Hensch¹⁴, Roee Holtzer¹⁵, Bradley T Hyman¹⁶, Frank R Lin¹⁷, Ann C McKee¹⁸, John C Morris¹⁹, Ronald C Petersen²⁰, Lisa C Silbert³, Robert G Struble²¹, John Q Trojanowski²², Joe Verghese¹⁵, Donald A Wilson²³, Shunbin Xu⁶, Li I Zhang²⁴

Affiliations

¹ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address: albers.mark@mgh.harvard.edu.
² Jack, Joseph and Morton Mandel School of Applied Social Sciences, Case Western Reserve University, Cleveland, OH, USA.
³ Department of Neurology, Oregon Heath & Science University, Portland, OR, USA.
⁴ SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego State University, San Diego, CA, USA.
⁵ Volen National Center for Complex Systems and Department of Psychology, Brandeis University, Waltham, MA, USA.
⁶ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁷ Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
⁸ Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
⁹ Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹⁰ Dept. of Neurology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.
¹¹ Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
¹² Bloedel Hearing Research Center, University of Washington, Seattle, WA, USA.
¹³ Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; Center on Aging, Medical University of South Carolina, Charleston, SC, USA.
¹⁴ Department of Molecular & Cellular Biology, Harvard University, Cambridge, MA, USA.
¹⁵ Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA.
¹⁶ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
¹⁷ Division of Otology, Neurotology, & Skull Base Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁸ Departments of Neurology and Pathology, Boston University School of Medicine, Bedford, MA, USA.
¹⁹ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
²⁰ Mayo Alzheimer's Disease Research Center, Mayo Clinic College of Medicine, Rochester, MN, USA.
²¹ Center for Alzheimer Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield, IL, USA.
²² Center for Neurodegenerative Disease Research and Institute on Aging, the Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA.
²³ Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
²⁴ Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

PMID: 25022540
PMCID: PMC4287457
DOI: 10.1016/j.jalz.2014.04.514

Review

At the interface of sensory and motor dysfunctions and Alzheimer's disease

Mark W Albers et al. Alzheimers Dement. 2015 Jan.

. 2015 Jan;11(1):70-98.

doi: 10.1016/j.jalz.2014.04.514. Epub 2014 Jul 9.

Authors

Affiliations

¹ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address: albers.mark@mgh.harvard.edu.
² Jack, Joseph and Morton Mandel School of Applied Social Sciences, Case Western Reserve University, Cleveland, OH, USA.
³ Department of Neurology, Oregon Heath & Science University, Portland, OR, USA.
⁴ SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego State University, San Diego, CA, USA.
⁵ Volen National Center for Complex Systems and Department of Psychology, Brandeis University, Waltham, MA, USA.
⁶ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁷ Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
⁸ Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
⁹ Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹⁰ Dept. of Neurology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.
¹¹ Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
¹² Bloedel Hearing Research Center, University of Washington, Seattle, WA, USA.
¹³ Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; Center on Aging, Medical University of South Carolina, Charleston, SC, USA.
¹⁴ Department of Molecular & Cellular Biology, Harvard University, Cambridge, MA, USA.
¹⁵ Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA.
¹⁶ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
¹⁷ Division of Otology, Neurotology, & Skull Base Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁸ Departments of Neurology and Pathology, Boston University School of Medicine, Bedford, MA, USA.
¹⁹ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
²⁰ Mayo Alzheimer's Disease Research Center, Mayo Clinic College of Medicine, Rochester, MN, USA.
²¹ Center for Alzheimer Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield, IL, USA.
²² Center for Neurodegenerative Disease Research and Institute on Aging, the Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA.
²³ Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
²⁴ Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

PMID: 25022540
PMCID: PMC4287457
DOI: 10.1016/j.jalz.2014.04.514

Abstract

Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled "Sensory and Motor Dysfunctions in Aging and AD." The scientific sessions of the workshop focused on age-related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses.

Keywords: Aging; Alzheimer's disease; Auditory function; Motor; Olfaction; Sensory; Vision.

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Figures

**Figure**
Models of the relationship between sensory/motor dysfunction and AD. A) A Clinical model. Seminal observations of dysfunction of each sensory/motor modality are documented at the earliest reported stage during the clinical course of AD based on the studies referenced in this review. Parallel progression of these initial sensory or motor dysfunctions to advanced AD dementia raises the question of whether AD may be a heterogeneous disease in origin or a disease with heterogeneous clinical courses. A comprehensive assessment of all relevant sensory and motor measures from the preclinical stage of AD to the advanced dementia stage may help to test this possibility. Future research may also aim to extend these findings to earlier periods of the preclinical AD stage with better sensitivity and specificity by either improving the measurement methodology for detecting sensory and motor changes or by combining sensory/motor measures with other biomarkers, such as CSF, neuroimaging, and genetic risk factors for AD. B) A cellular model. A schematic framework of disease progression where the light gray neurons represent dysfunctional neurons. In this model, dysfunction arises sporadically and then propagates in a pattern that is instructed by the connectivity of the involved neurons, circuits, networks, and systems. Since we speculate that disease initiation is sporadic, the involved circuits and networks at the earliest stages will likely differ between individual patients. This model may be tested by further research with AD-related model organisms to assess the mechanisms of disease progression from a sensory or motor domain to the cognitive domain and to investigate the effects of early intervention on early sensory or motor dysfunction and on prevention of progression to cognitive impairment.

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References

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At the interface of sensory and motor dysfunctions and Alzheimer's disease

Affiliations

At the interface of sensory and motor dysfunctions and Alzheimer's disease

Authors

Affiliations

Abstract

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical