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      Long-Term Efficacy of Memantine in Parkinson' Disease Dementia: An 18-Month Prospective Perfusion Single Photon Emission Computed Tomography Preliminary Study

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          Abstract

          Background and Purpose

          Although the treatment efficacy of memantine in Parkinson's disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using 99mTc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT).

          Methods

          A total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD.

          Results

          The PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR ( p=0.32), sum of box of CDR ( p=0.49), MMSE ( p=0.61), GDS ( p=0.79), and NPI ( p=0.23) were not significant in the PDD patients.

          Conclusions

          Our findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.

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          Most cited references21

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          BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease.

          Robert Phillips, B J Winslow, Isla Hains … (1991)
          In recent years, nerve growth factor (NGF) has gained attention as a potential therapeutic agent for Alzheimer's disease (AD). To study the expression of NGF and its homologs, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3), postmortem samples of hippocampus from AD and control donors were examined by in situ hybridization. Hybridization signal for BDNF, but not NGF or NT-3, was decreased in samples of hippocampus from donors with AD. Decreased transcript abundance of BDNF mRNA in hippocampi of individuals with AD was verified by an RNAase protection assay. These results suggest the possibility that decreased expression of BDNF may contribute to the progression of cell death in AD.
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            Caregiver-burden in parkinson's disease is closely associated with psychiatric symptoms, falls, and disability.

            Niall Quinn, David Morley, Anna Hovris … (2005)
            The majority of care of patients with Parkinson's disease (PD) is provided by informal caregivers; their caregiving not only offers physical and emotional support for patients but also plays a large economic role and prevents early nursing home placement. In order to support caregivers in this role, it is necessary to understand the extent of caregiver-burden and factors associated with increased caregiver-burden and distress. We therefore conducted a postal survey in 123 caregivers of patients with PD to assess caregiver-burden and factors associated with it. The majority of caregivers were female (66%). Over 40% of caregivers indicated that their health had suffered as a result of caregiving, almost half had increased depression scores, and two-thirds reported that their social life had suffered. After adjustment of disease duration, there was no difference in caregiver-burden between younger and older caregivers, or between male and female caregivers. Caregiver-burden increased with increasing disability and symptoms of PD, particularly with mental health problems such as depression, hallucinations, or confusion, and with falls. Caregiver-burden scores also correlated significantly with the patients' depression and quality of life scores, and with caregivers' own satisfaction with their marital and sexual relationship. We conclude that more attention should be paid to caregivers' emotional and physical health, particularly in advancing PD with psychiatric complications and falls. These findings also demonstrate that caregiver and patient quality of life are closely linked and emphasize the importance of including caregiver-burden among the problems associated with PD in order to improve patient and caregiver lives.
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              Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study.

              Nicolaas Bohnen, Daniel Kaufer, Larry Ivanco … (2003)
              Pathology reports have shown that cholinergic forebrain neuronal losses in parkinsonian dementia (PDem) are equal to or greater than those in Alzheimer disease (AD). We hypothesized that patients with PDem would have cholinergic deficits that were similar to or greater than those of patients with AD. To determine in vivo cortical acetylcholinesterase (AChE) activity in healthy control subjects and in patients with mild AD, PDem, and Parkinson disease without dementia using AChE positron emission tomography. University and Veterans' Administration medical center. Design and Patients Group comparison design of patients with AD (n = 12), PDem (n = 14), and Parkinson disease without dementia (n = 11), and controls (n = 10) who underwent AChE imaging between July 1, 2000, and January 31, 2003. Patients with AD and PDem had approximately equal dementia severity. Cerebral AChE activity. Compared with controls, mean cortical AChE activity was lowest in patients with PDem (-20.0%), followed by patients with Parkinson disease without dementia (-12.9%; P<.001). Mean cortical AChE activity was relatively preserved in patients with AD (-9.1%), except for regionally selective involvement of the lateral temporal cortex (-15%; P<.001). Reduced cortical AChE activity is more characteristic of patients with PDem than of patients with mild AD.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Dement Neurocogn Disord
                Journal ID (iso-abbrev): Dement Neurocogn Disord
                Journal ID (publisher-id): DND
                Title: Dementia and Neurocognitive Disorders
                Publisher: Korean Dementia Association
                ISSN (Print): 1738-1495
                ISSN (Electronic): 2384-0757
                Publication date (Print): June 2016
                Publication date (Electronic): 30 June 2016
                Volume: 15
                Issue: 2
                Pages: 43-48
                Affiliations
                [1 ]Department of Nuclear Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
                [2 ]Department of Neurology, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
                [3 ]Department of Neurology, Veterans Hospital, Seoul Medical Center, Seoul, Korea.
                Author notes
                Correspondence: In-Uk Song, MD, PhD. Department of Neurology, Incheon St. Mary's Hospital, The Catholic University of Korea, 56 Dongsu-ro, Bupyeong-gu, Incheon 21431, Korea. Tel: +82-32-280-5010, Fax: +82-32-280-5244, siuy@ 123456cmcnu.or.kr
                Article
                DOI: 10.12779/dnd.2016.15.2.43
                PMC ID: 6427978
                SO-VID: cef595e9-e4c1-45f5-aabf-92bd69871186
                Copyright © © 2016 Korean Dementia Association
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 02 June 2016
                Date revision received : 14 June 2016
                Date accepted : 14 June 2016
                Funding
                Funded by: National Research Foundation of Korea, CrossRef http://dx.doi.org/10.13039/501100003725;
                Award ID: NRF-2015M3C7A1064832
                Categories
                Subject: Original Article

                Keywords: parkinson's disease dementia,memantine,single photon emission computed tomography,brain perfusion,cognitive function
                Data availability:
                Keywords: parkinson's disease dementia, memantine, single photon emission computed tomography, brain perfusion, cognitive function

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