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Clinical Utility and Safety of an Ultrasonic Head Stimulator in Dementia With Lewy Bodies

Yuta Manabe

Alzheimer Disease & Associated Disorders 2024, 39, 33-38 · 10.1097/wad.0000000000000652

human patientotherclinical scaleautonomic physiology

Abstract

Background The potential of Ultra-Ma, an ultrasonic head stimulator, for the supplementary treatment of dementia with Lewy bodies (DLB) was evaluated in patients with various symptoms under poor control by drug therapy. Methods Patients with DLB treated with choline esterase inhibitor or L-DOPA, either alone or in combination, and who met inclusion criteria were enrolled. Four weeks of placebo stimulation was followed by 8 weeks of active ultrasonic stimulation and a 4-week follow-up. Primary endpoints were the effects of ultrasonic head stimulation on both cognitive dysfunction and behavioral and psychological symptoms of dementia (BPSD). Cognitive dysfunction was evaluated using the Japanese versions of the Mini-Mental State Examination and Montreal Cognitive Assessment, and BPSD was assessed using the Neuropsychiatric Inventory Brief Questionnaire Form. For cognitive fluctuations, the Cognitive Fluctuation Inventory served as an index. Improvements in parkinsonism, activities of daily living, and caregiver burden were examined as secondary endpoints. Results Twelve patients were enrolled. The primary endpoint was significantly improved during the active stimulation period, as were secondary endpoint ratings for parkinsonism and caregiver burden. No notable adverse events occurred. Conclusions The findings suggest that ultrasonic head stimulation has supplementary potential when combined with drug treatment in DLB.

Abstract via europepmc.

Specieshuman
Subjects12 participants
Sessions per subjectnot reported
Randomisedno
Blindingnone
Sham / controlundescribed
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsclinical scale, autonomic physiologyMMSE-J, MoCA-J, NPI-Q severity/distress, Cognitive Fluctuation Inventory (CFI), MDS-UPDRS Part III, Barthel Index, J-Zarit-8; sphygmomanometry, pulse rate, blood biochemistry, electrocardiography
Direction of effectmixed or unclearActive ultrasonic stimulation significantly improved MMSE-J at week 8, NPI-Q severity and distress and MDS-UPDRS Part III at week 12, and CFI from week 12 onward, versus baseline; MoCA-J and Barthel Index showed no significant change at any timepoint; most improvements (except CFI and J-Zarit-8) were not sustained at the 4-week follow-up.
Adverse eventsnone observedNo adverse events were noted. In addition, blood biochemistry and electrocardiography were performed during the screening period and at the end of the clinical study instrumentation period (week 12), and no clinically significant change suggestive of any association with the study device was identified.

Exposures

Exposure 1: Ultra-Ma ultrasonic head stimulation (active stimulation period)

Target: whole brain or unfocused — “head
Device: other named manufacturer · Kamiyama Mfg. Co., Ltd. · Ultra-Ma (development code KMY-01)

Pulse timing
Waveformnot reported
Fundamental frequency (kHz)30✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)1,200✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)0.0016✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Four weeks of placebo stimulation was followed by 8 weeks of active ultrasonic stimulation and a 4-week follow-up period. Patients underwent ultrasonic stimulation using the ultrasonic head stimulator for 20 minutes per session, twice daily (session 1 at 10:00 AM +/- 2 h; session 2 at 3:00 PM +/- 2 h). A massage band supplying weak ultrasound to the head was connected to the main body of the device via the No. 1 output terminal jack during placebo stimulation and via the No. 2 output terminal jack during active stimulation.

Flags from extraction

  • exposures[0].free_field.isppa_w_cm2Paper reports 'maximum output' and 'average output' in mW/cm² measured in water, but never uses the terms ISPPA or ISPTA; the maximum value is recorded here as the closest available spatial-peak intensity, and the spatially-averaged 0.71 mW/cm² value has no field to record it in.
  • exposures[0].timing.waveformThe paper never describes whether the 30 kHz output is continuous or pulsed (no PRF, pulse duration or duty cycle given).
  • n_sessions_per_subjectPaper states session frequency (twice daily, 20 min) and period lengths in weeks but never states a total session count; computing one would require arithmetic not shown in the text.
  • sham_typePlacebo condition used a different output jack (No. 1) on the same device; the paper never explains what output, if any, that jack produced.
  • conditionsDementia with Lewy bodies is not in the closed vocabulary; recorded as other + condition_other.