Table 1.

European plants and their constituents with relevance for dementia: cognition

Plant name*, part, and phytochemicals associated with biological activities	Traditional uses	Relevant bioactivities	Clinical effects/observations in humans
Snowdrop	Galanthus and other Amaryllidaceae species: not commonly used as medicines in Europe; more recently (approx. last 40 years) used to alleviate various neurological conditions in Europe, particularly Bulgaria [22].	Galantamine is a well‐documented AChE inhibitor and a positive allosteric modulator of nicotinic receptors [16].  Numerous synthetic galantamine derivatives have been developed including derivatives of 6‐O‐demethylgalantamine; some heterodimeric alkylene linked bis‐galantamine derivatives inhibit AChE more potently than galantamine [16]. In animal models of amnesia, a prodrug of galantamine (Memogain®) improves cognition more effectively, with fewer side‐effects, than galantamine [23].  Other alkaloids from Narcissus species inhibit AChE: 11‐hydroxygalantamine, epinorgalantamine, assoanine, and sanguinine [16].	Numerous multi‐center, RCTs show galantamine is well‐tolerated and significantly improves cognitive function in AD patients [14, 24].  Galantamine may also be of some therapeutic value in LBD and VaD [16].
Galanthus species
Daffodil/narcissus
Narcissus species
Leucojum aestivum L. (Amaryllidaceae)
Bulbs
Alkaloids: particularly galantamine
Lemon balm/melissa	Reputed in European medicine to treat melancholia, neuroses, and hysteria; acclaimed for promoting long life and restoring memory [16].	An ethanolic extract, the essential oil, and some oil components (citral) weakly inhibit AChE; rosmarinic acid and derivatives are also associated with AChE inhibition [16].	Improved cognitive performance in healthy participants in RCTs following treatment with cholinergically active M. officinalis dried leaf or a standardized extract; cognitive improvements observed in AD patients treated with M. officinalis extract for 4 months in a double‐blind RCT [15, 16].
Melissa officinalis L. (Lamiaceae)
Aerial parts
Essential oil; rosmarinic acid and derivatives		Other activities: antioxidant, possible estrogenic, binding to muscarinic M1, nicotinic, 5‐HT1A, 5‐HT2A, histamine H3, and GABAA receptors; essential oil inhibits GABA‐induced currents in rat cortical neurons [16, 25, 26].
Sage	Used traditionally in European medicine for memory disorders; its use is quoted in 16th and 17th century English herbals [15].	Various CNS effects reported for different Salvia species including memory enhancing, neuroprotective, and antiparkinsonian activities [27].  Extracts and oils from S. officinalis and S. lavandulifolia are antioxidant, antiinflammatory, and inhibit AChE; the latter activity is associated with oil monoterpenoids (1,8‐cineole and α‐pinene) [24, 28, 29].	A standardized oil extract of S. lavandulifolia produced significant effects on cognitive ability (immediate word recall scores improved) in healthy young adults (RCT) [30]. A similar study showed positive modulation of mood and cognition in healthy young adults given standardized essential oil of S. lavandulifolia[31].  S. officinalis extract enhanced secondary memory performance in adults (> 65 yr age, RCT) [32].  In a pilot trial (11 patients with mild to moderate AD) S. lavandulifolia oil significantly improved cognitive function, reduced neuropsychiatric symptoms, and improved attention [33].  In a multi‐center RCT, AD patients treated with S. officinalis extract had significantly better outcomes in cognitive function [34].
Salvia species, in particular:
S. officinalis L. and S. lavandulifolia Vahl. (Lamiaceae)
Aerial parts
Monoterpenoids including 1,8‐cineole and α‐pinene
Lesser periwinkle	A folk medicine used for loss of memory and circulatory disorders [35].	Vincamine and derivatives (vincanol and vinpocetine) show cerebral vasodilator/nootropic activity, block voltage‐gated Na+ channels, and are neuroprotective [36, 37].  Vincamine modulates brain circulation and neuronal homeostasis and is antihypoxic [35].  However, alkaloid fractions extracted from aerial parts are cytotoxic in vitro[35].	Double‐blind studies have assessed efficacy of vinpocetine in dementia but quality of methods is limited; a 16‐week double‐blind RCT (203 patients: mild to moderate dementia) showed significant benefit in the vinpocetine treated group [38].  Although a lack of evidence to support clinical use of vinpocetine in cognitive disorders [39], it improved cognitive status and cerebrovascular reserve capacity in patients with ischemic stroke and MCI in a pilot study [40].
Vinca minor L. (Apocynaceae)
Aerial parts
Alkaloids: vincamine

*Common and Latin names (plant family).