Neurology -- Correspondence for Boyle et al., 65 (12) 1901-1906

Correspondence published:

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
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Re: Parkinsonian signs in subjects with mild cognitive impairment

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
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Re: Reply from the Authors

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.