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ARTICLES:
P. A. Boyle, R. S. Wilson, N. T. Aggarwal, Z. Arvanitakis, J. Kelly, J. L. Bienias, and D. A. Bennett
Parkinsonian signs in subjects with mild cognitive impairment
Neurology 2005; 65: 1901-1906
[Abstract][Full text][PDF]
Parkinsonian signs in subjects with mild cognitive impairment
Barbara Vicini Chilovi, Luca Rozzini, Alessandro Padovani
(18 April 2006)
Reply from the Authors
Patricia A. Boyle, Robert S. Wilson, David A. Bennett
(18 April 2006)
Parkinsonian signs in subjects with mild cognitive impairment
18 April 2006
Barbara Vicini Chilovi, Department of Neurology, University of Brescia Piazzale Spedali Civili, 1, 25100, Brescia, Italy, Luca Rozzini, Alessandro Padovani
barbaravicini{at}tiscali.it Barbara Vicini Chilovi, et al.
We read the article by Boyle et al with interest. The authors report that Mild Cognitive Impairment (MCI) is
accompanied by extrapyramidal signs (EPS) which are related to the
severity and type of cognitive impairment independent of vascular risk
factors. [1]
The association between Mild Parkinsonian Signs (MPS) and MCI has previously been described; specifically the relationship between MPS and the amnestic type (aMCI). [2] Furthermore,
rigidity rather than tremor or bradykinesia were most strongly associated
with MCI.
We analyzed data from a large group of MCI patients
consecutively recruited in the last three years at the Neurological
Clinic, University of Brescia, Italy. Participants underwent a clinical
and neurological assessment including the Unified Parkinson Disease scale
(UPDRS part III), the Neuropsychiatric Inventory (NPI), the Tinetti Scale,
and a standardized neuropsychological battery. A designation of MCI was
made according to published criteria. [3]
EPS were defined as present if
total score UPDRS part III >2, and > 1 in two or more of the three
items:bradykinesia, rigidity or tremor. Among 147 MCI patients, 41 (27,9%) had mild to moderate EPS (UPDRS part III: MCI+= 9,4 ± 7,5) while 106
(72,1%) had no EPS (UPDRS part III: MCI- = 1,1± 1,5). The two groups were
similar in age, gender, and education and in clinical
characteristics with the exception of gait abnormalities (Tinetti Scale:
MCI+= 25,6 ± 2,7; MCI-= 27,5± 1,3; p<.0001).
The two groups did not
differ for general cognitive functions evaluated through the Mini Mental
State Examination (MMSE total score, MCI-=27,1± 1,2; MCI+= 26,9± 1,3).
MCI+ subjects showed a lower performances compared to MCI- on every
neuropsychological domains, even if not significantly.
However, through a
series of linear regression models, severity of EPS was found to be
significantly correlated with performances on the MMSE (p<.05) and on
the Rey Figure Copy (p<.01). More importantly, there was a significant
association between presence of EPS and behavioral disturbances (NPI
total score: MCI+ 18,8 ± 11,3; MCI-= 11,9 ± 11,2; p<.05), particularly
in terms of hallucinations, apathy, and sleep disorders.
These findings confirm the assumption that MCI is associated with
parkinsonian signs, the severity of which is related to the severity and differential pattern of both cognitive and behavioral dysfunctions.
The association between EPS and specific behavioral disturbances included
in the core features of DLB [4] suggests that Lewy body pathology
might be the major contributing factor to both EPS and BPSD.
In addition, neuropsychological data showed that
MCI+ subjects had a greater deterioration of visuo-spatial skills primarily compromised in DLB. [5] Further studies are needed to follow-up those MCI patients with EPS to determine whether they have a more
rapid progression to dementia.
References
1. Boyle PA, Wilson RS, Aggarwal NT et al. Parkinsonian signs in
subjects with mild cognitive impairment. Neurology 2005;65:1901-1906.
2. Louis ED, Schupf N, Manly J, et al. Association between mild
parkinsonian signs and mild cognitive impairment in a community.Neurology.
2005;12;64:1157-61.
3. Petersen RC, Doody R, Kurz A et al. Current concept in mild cognitive
decline. Arch Neurol 2001;58: 1985-92.
4. McKeith IG, Dickson DW, Lowe J et al. Diagnosis and management of
dementia with Lewy bodies: third report of the DLB Consortium. Neurology.
2005;27;65:1863-72.
5. Cummings JL. Demenia with Lewy bodies: molecular pathogenesis and
implications for classification. J Geriatr Psychiatry Neurol 2004;17:112-
119.
Disclosure: The authors report no conflicts of interest.
Reply from the Authors
18 April 2006
Patricia A. Boyle, Rush Alzheimer's Disease Center 600 South Paulina, 1020B, Chicago, IL 60612, Robert S. Wilson, David A. Bennett
Patricia_Boyle{at}rush.edu Patricia A. Boyle, et al.
We thank Chilovi et al for their interest in our recent findings
showing that parkinsonian signs are common among community-based persons
with mild cognitive impairment (MCI) and are associated with the severity
and type of cognitive impairment.
Their data from a cohort
of patients provides additional support for the association of
parkinsonian signs with cognitive function in MCI. Their findings also
suggest that parkinsonian signs may be related to behavioral disturbances,
particularly hallucinations, apathy, and sleep disorders. Their data are
consistent with a growing body of evidence linking motor[1,2], cognitive,
and behavioral [6] symptoms in MCI.
The recent findings on the non-cognitive manifestations of MCI [1,2,6]
have two important implications. First, although the classification of
MCI typically is based on the presence of cognitive impairment, persons
with MCI exhibit a much broader range of symptoms including motor and
behavioral impairment. Second, the co-occurrence of cognitive and non-
cognitive symptoms may indicate a shared pathogenesis.
Chilovi et al
hypothesized that Lewy body pathology underlies the motor and behavioral
disturbances observed in MCI. We agree that common age-related
neuropathologies likely play a role in the development and expression of
non-cognitive symptoms in older persons. However, pathologic findings
suggest that MCI represents the earliest manifestation of dementia,
especially AD. [7] We suspect that AD pathology may be an important
contributor to motor dysfunction in MCI, in addition to cognitive
impairment. For example, it was recently reported that there is an
association between neurofibrillary tangles in the substantia nigra and
motor dysfunction, particularly gait disturbance, in older persons with
and without dementia. [8]
We agree with Chilovi et al that future studies are needed to
determine the prognostic importance of non-cognitive symptoms in MCI.
Additional studies also are required to determine the extent to which AD
pathology and other common age-related neuropathologies contribute to
motor dysfunction and other non-cognitive manifestations of MCI.
References
6. Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric
symptoms in dementia and mild cognitive impairment: results from the
cardiovascular health study. JAMA 2002;288:1475-83.
7. Bennett DA, Schneider JA, Bienias JL, et al. Mild cognitive impairment
is related to Alzheimer disease pathology and cerebral infarctions.
Neurology 2005;64:834-41.
8. Schneider JA, Li JL, Li Y, et al. Substantia nigra tangles are related
to gait impairment in older persons. Ann Neurol 2006;59:166-73.
Disclosure: The authors report no conflicts of interest.