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Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia.

Chow TW, Graff-Guerrero A, Verhoeff NP, Binns MA, Tang-Wai DF, Freedman M, Masellis M, Black SE, Wilson AA, Houle S, Pollock BG - Neuropsychiatr Dis Treat (2011)

Bottom Line: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD), and the mechanism of action may not be specific to AD alone.The increase on FDG-PET did not correlate with changes on behavioral inventories.This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurology, Baycrest.

ABSTRACT

Background: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD), and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.

Methods: Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD) were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7-8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.

Results: Voxel-wise parametric image analysis of positron emission tomography (PET) data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [(18)F]-fluorodeoxyglucose (FDG) normalized metabolic activity in bilateral insulae and the left orbitofrontal cortex (P < 0.01). The increase on FDG-PET did not correlate with changes on behavioral inventories. Post hoc analysis indicated that semantic dementia participants drove this finding.

Conclusion: This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD. A placebo-controlled follow-up study is warranted.

No MeSH data available.


Related in: MedlinePlus

Flowchart for recruitment, including early withdrawals.
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f1-ndt-7-415: Flowchart for recruitment, including early withdrawals.

Mentions: Figure 1 shows our recruitment flowchart, including early withdrawals. Except for one serious adverse event leading to early withdrawal from the study, early withdrawals occurred prior to start of memantine. Early withdrawals were compared with study completers with respect to their demographic data using Chi-squared tests and independent-samples t-tests. Baseline characterization of participants who withdrew or were withdrawn from the study early showed no significant group differences from study completers in gender ratio, age at the time of study enrolment, age at onset of FTD or duration of illness, but the included group (n = 16) had a higher mean educational level (16.9 ± 2.8 years) than the excluded group (mean 13.5 ± 3.7 years, independent-samples t-test, P = 0.012). Behavioral and functional inventories were only conducted for two of the nine early withdrawals and for one participant whose imaging data could not be used. The only pertinent observation was that the Stereotypy Rating Inventory scores for the three excluded participants were 0, 0, and 8, compared with an average of 11.76 from the 16 study completers.


Open-label study of the short-term effects of memantine on FDG-PET in frontotemporal dementia.

Chow TW, Graff-Guerrero A, Verhoeff NP, Binns MA, Tang-Wai DF, Freedman M, Masellis M, Black SE, Wilson AA, Houle S, Pollock BG - Neuropsychiatr Dis Treat (2011)

Flowchart for recruitment, including early withdrawals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140294&req=5

f1-ndt-7-415: Flowchart for recruitment, including early withdrawals.
Mentions: Figure 1 shows our recruitment flowchart, including early withdrawals. Except for one serious adverse event leading to early withdrawal from the study, early withdrawals occurred prior to start of memantine. Early withdrawals were compared with study completers with respect to their demographic data using Chi-squared tests and independent-samples t-tests. Baseline characterization of participants who withdrew or were withdrawn from the study early showed no significant group differences from study completers in gender ratio, age at the time of study enrolment, age at onset of FTD or duration of illness, but the included group (n = 16) had a higher mean educational level (16.9 ± 2.8 years) than the excluded group (mean 13.5 ± 3.7 years, independent-samples t-test, P = 0.012). Behavioral and functional inventories were only conducted for two of the nine early withdrawals and for one participant whose imaging data could not be used. The only pertinent observation was that the Stereotypy Rating Inventory scores for the three excluded participants were 0, 0, and 8, compared with an average of 11.76 from the 16 study completers.

Bottom Line: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD), and the mechanism of action may not be specific to AD alone.The increase on FDG-PET did not correlate with changes on behavioral inventories.This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurology, Baycrest.

ABSTRACT

Background: Memantine has shown effects on cortical metabolism in Alzheimer's disease (AD), and the mechanism of action may not be specific to AD alone. We hypothesized that participants with frontotemporal dementia taking memantine would show an increased cortical metabolic activity in frontal regions, temporal regions, or in salience network hubs.

Methods: Sixteen participants with behavioral or language variant frontotemporal dementia syndromes (FTD) were recruited from tertiary FTD clinics and treated with memantine hydrochloride 10 mg twice daily in this fixed-dose, open-label pilot study. The primary endpoint was enhancement of cortical metabolic activity after 7-8 weeks of treatment. Secondary endpoints were measures of mood and behavior disturbance, frontal executive function, and motor disturbance.

Results: Voxel-wise parametric image analysis of positron emission tomography (PET) data from seven behavioral variant FTD patients, eight semantic dementia patients, and one progressive nonfluent aphasia patient, of mean age 64.3 years, mean duration of illness 4.25 years, and baseline mean sum of boxes Clinical Dementia Rating score 6.59, revealed an increase in [(18)F]-fluorodeoxyglucose (FDG) normalized metabolic activity in bilateral insulae and the left orbitofrontal cortex (P < 0.01). The increase on FDG-PET did not correlate with changes on behavioral inventories. Post hoc analysis indicated that semantic dementia participants drove this finding.

Conclusion: This open-label clinical PET study suggests that memantine induces an increase in metabolism in the salience network in FTD. A placebo-controlled follow-up study is warranted.

No MeSH data available.


Related in: MedlinePlus