Table 1.

Summary of papers that detail the use of brain stimulation using external stimuli applied to AD patients

Author, Year and Reference	Stimulus Type	Stimulus Frequency	Stimulus Delivery Method	Patient Cohort	Outcome Measure	Results	Notes
Da Silva 2015 about Vieira 2008 [91, 92]	Light and sound combined	1–30 Hz	Strobing LED lamps in inner lenses of sunglasses, binaural beats through headphones	37 male and female, aged 68–78 with AD	EEG for cortical performance	Increase in both performance and cortical performance compared to unstimulated group	Stimulation while performing cognitive task requiring high levels of memory
Clements-Cortes 2016 [93, 98, 99]	Somatosensory (vibrotactile)	40 Hz: (39.96–40.06 Hz to prevent habituation)	6 sessions of sound played via 6 chair speakers. Program cycling through amplitude modulation, direction of movement and sound pressure	6 mild, 6 moderate and 6 severe AD patients. 10 male, 8 female, aged 59–93	SLUMS test	Statistically significant difference - average improvement of 0.5 units in SLUMS per session. Mild and moderate most affected	Behavioral endpoint given
Naro 2016 [102]	tACS (transcranial alternating current stimulation)	10-min stimulation continuously and randomly from 40–120 Hz (at discrete 20 Hz step values)	Saline soaked rectangular sponge electrode with active electrode over one of five locations and reference electrode over right mastoid. (5 separate tests done covering each active site)	35 AD patients, 25 mild cognitive impairment (MCI) patients, 27 healthy control participants	Neuropsychological tests and EEG recording of gamma band oscillations (GBO) power	Demonstrated ability to differentiate AD and MCI patients as well as ability to identify MCI patients at high risk of developing AD	Uniquely is example of using brain stimulation for diagnostic purpose
Calomeni 2017 [104]	Light and sound, (Concurrent?)	8 Hz, 10 Hz, 12 Hz, 14 Hz and 15 Hz	10×15 min stimulation sessions over 20-day period	15 elderly (81±6 y) with AD and 15 elderly (76±8) without dementia	Digit span cognitive test and EEG	Average alpha wave increase and improvement on cognitive performance in all participants	15-min ‘training’ confounder
Basar 2017 [105]	Visual	Stimulus on for 1 s and then off for between 3–7 s	White screen flashing on and off and visual oddball paradigm	39 probable mild AD (21 untreated, 18 treated) and 21 matched healthy controls	EEG gamma coherences measured at 25–30 Hz, 30–35, and 40–48 Hz bands	Increase in gamma band activity in all participants for both stimuli. Significantly larger response in the AD patients compared to normal participants. Increase in gamma response was not affected by drug therapy in AD cohort.	Event related stimulus could be interpreted as a cognitive stimulus
Huei-Tsai 2018 [108, 110]	Light, sound and tactile. (Concurrent?)	40 Hz	Flickering light, low sounds and vibrating pads located on hands to humans with AD. 40 Hz sound to mice	12 AD patients – mild and moderate	Study of mouse tissue	In mice, 40 Hz sound caused reduction of about half of amyloid plaques in auditory cortex and in the hippocampus	No placebo group for human trial. Significant that sounds cause reduction of amyloid plaques in mice hippocampus