Therapeutic Strategies and Drug Development for Vascular Cognitive Impairment

Eric E Smith, Alicja Cieslak, Philip Barber, Jerry Chen, Yu-Wei Chen, Ida Donnini, Jodi D Edwards, Richard Frayne, Thalia S Field, Janka Hegedus, Victoria Hanganu, Zahinoor Ismail, Jamila Kanji, Makoto Nakajima, Raza Noor, Stefano Peca, Demetrios Sahlas, Mukul Sharma, Luciano A Sposato, Richard H Swartz, Charlotte Zerna, Sandra E Black, Vladimir Hachinski, Eric E Smith, Alicja Cieslak, Philip Barber, Jerry Chen, Yu-Wei Chen, Ida Donnini, Jodi D Edwards, Richard Frayne, Thalia S Field, Janka Hegedus, Victoria Hanganu, Zahinoor Ismail, Jamila Kanji, Makoto Nakajima, Raza Noor, Stefano Peca, Demetrios Sahlas, Mukul Sharma, Luciano A Sposato, Richard H Swartz, Charlotte Zerna, Sandra E Black, Vladimir Hachinski

No abstract available

Keywords: cerebrovascular disease; clinical trials; cognitive impairment; stroke; systematic review; vascular dementia.

Figures

Figure 1
Figure 1
Trial design considerations categorized by population (A), intervention (B), and outcome (C). AD indicates Alzheimer disease; CADASIL, cerebral autosomal dominant arteriopathy with subcortical ischemic leukoencephalopathy; MCI, mild cognitive impairment; VCI, vascular cognitive impairment .
Figure 2
Figure 2
Flow chart showing study selection. ALOIS indicates the Cochrane Dementia and Cognitive Improvement Group's Specialized Register; VCI, vascular cognitive impairment.
Figure 3
Figure 3
Published randomized controlled trials of pharmacological and nonpharmacological treatments for VCI. Data were abstracted from 130 eligible trials. The area of the bubble is linearly proportional to the total randomized sample size. Bubbles are color coded according to the presumed mechanism of action. “Multiple” indicates that the trial compared drugs or strategies with more than 1 mechanism, with or without an additional untreated control group. Nonpharmacological strategies included group therapy, acupuncture, and transcranial magnetic stimulation or direct current stimulation. NMDA, N‐methyl‐d‐aspartate.
Figure 4
Figure 4
Drug development status of medications for patients with vascular cognitive impairment. Phase III was operationally defined retrospectively as randomized controlled trials with ≥300 participants, later phase II as ≥100 to 299 participants, and early phase II as <100 participants. Data from trials with untreated controls (mostly receiving a placebo) were used to generate the figure. A single large trial (>300 participants) of the calcium channel blockers nicardipine vs clentiazem was not included because there was no untreated control arm.

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