title: Substantia nigra tangles are related to gait impairment in older persons.
abstract: OBJECTIVE
  Parkinsonian signs, especially gait impairment, are common and associated with morbidity and mortality in older persons. Our objective was to test the hypothesis that substantia nigra neurofibrillary tangles (NFTs) are related to parkinsonian signs in older persons with and without dementia.
  
  
  METHODS
  We studied 86 deceased older Catholic clergy without idiopathic Parkinson's disease from the Religious Order Study, a longitudinal clinical-pathological study. Mean age at death was 85.3 years. Signs of gait disturbance, bradykinesia, rigidity, and tremor were assessed proximate to death using a modified Unified Parkinson's Disease Rating Scale. Forty-micrometer paraffin-embedded sections of substantia nigra were bleached before tau immunohistochemistry and the optical disector was used to count NFTs. We used multivariable linear regression to examine parkinsonian signs as a function of nigra NFTs, controlling for age, sex, education, and cortical NFTs.
  
  
  RESULTS
  Substantia nigra NFTs were present in 67 of 86 persons (77.9%). After controlling for age, sex, education, and cortical NFTs, nigra NFTs were related to gait impairment (p < 0.001), but not bradykinesia, rigidity, or tremor. Results were not confounded by dementia, Braak score, neuroleptic medication, cerebral infarcts, or Lewy bodies.
  
  
  CONCLUSIONS
  NFTs in the substantia nigra are associated with gait impairment in older persons with and without dementia.
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, 600 S. Paulina Street, Chicago, IL, USA. julie_a_schneider@rush.edu
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: Jia-liang
authors.initials: JL
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wilson
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Kordower
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology* / Q000502:physiology; D003704:Dementia / Q000473:pathology / Q000503:physiopathology; D020233:Gait Disorders, Neurologic / Q000473:pathology*; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology*; D010300:Parkinson Disease / Q000145:classification / Q000473:pathology / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013378:Substantia Nigra / Q000473:pathology*