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. Author manuscript; available in PMC: 2015 Mar 1.
Published in final edited form as: Am J Geriatr Psychiatry. 2013 Jul 23;22(3):216–240. doi: 10.1016/j.jagp.2013.02.017

Table 2.

Brain stimulation techniques for the treatment of dementia in older adults.

Publication Aim Subjects (n, sex) Age (Mean (StdDev) [Range]) Diagnosis Technique Method Outcome Measures Findings
(Mulsant et al., 1991) (also reported in Table 1) To describe the effect of ECT treatment on the mood, cognition, and medical status of older adults with depression. 40 (F=35) 73.5 (7.3) [60–89] MDD (n=25 including 10 with Psychotic depression). Bipolar disorder, depression (n=9). Organic mental disorder with major depressive syndrome (n=8). ECT (8.3 (2.6) [4–13] sessions), unilateral only (n=29), bilateral only (n=3), unilateral then bilateral (n=10). Prospective study (Participants: non-blind, Assessors: non-blind, Control conditions: none) HDRS, BPRS, MMSE

  • In addition to what is reported in Table 1, most patients, especially those with dementia (N = 8), experienced a significant increase in MMSE,

  • 13 out of the 40 patients experienced confusion between ECT sessions.

  • MMSE did not predict confusion
(Rao and Lyketsos, 2000) (also reported in Table 1) To describe the impact of ECT in treating older adults with dementia and concurrent depression. 31 (F=25) 75.6 (9.9) [55–97] AD (n=4), Vascular dementia (n=17), Degenerative dementia of uncertain etiology (n=10) ECT, unilateral or bilateral (1–23 sessions) Retrospective chart review, 1991–1996 MADRS, MMSE, CGI

  • In addition to what is reported in Table 1, there was improvement in cognition: MMSE mean increase of 1.62 points from admission score of 18.8
(Grant and Mohan, 2001) To describe the clinical course of four older adults with dementia treated with ECT for agitation and aggression. 4 (F=3) 72.3 (10.8) [56–78] AD (n=2). Dementia, unclassified (n=2) ECT Case series Clinical assessment

  • Improvement in symptoms associated with dementia

  • Effects lasted 3 to 12 months after 2–4 ECT sessions
(McDonald and Thompson, 2001) To describe the treatment of mania in conjunction with dementia in older adults with ECT 3 (F=?) older adults Mania, dementia ECT, unilateral (short course followed by maintenance ECT) Case series Clinical assessment

  • Improvement in symptoms of mania and agitation

  • Improved cognition
(Sjogren et al., 2002) To evaluate the cognitive-enhancing effects of VNS in treating older adults with AD. 10 (F=8) 67 (7.6) [57–78] AD, probable VNS Prospective pilot study (Participants: blind during 2 week surgical recovery period, Assessors: non-blind, Control conditions: none) Alzheimer’s Disease Assessment Scale-cognitive (ADAS-Cog), MMSE, Gottfries-Brane-Steen scale, CGI

  • 3 months post-VNS: 7/10 participants responded to treatment as measured by ADAS-Cog (median improvement of 3 points) and 9/10 participants responded to treatment as measured by MMSE (median improvement of 1.5 points)

  • 6 months post-VNS: 7/10 participants responded to treatment as measured by ADAS-Cog and MMSE

  • Adverse effects mild and transient
(Cotelli et al., 2006) To assess the effect of rTMS applied to the dorsolateral prefrontal cortex on picture naming in older adults with mild to moderate AD. 15 (F=?) 76.7 (6.0) AD, probable rTMS (1 × 600 ms at 20 Hz) Experimental study (Participants: blind, Assessors: non-blind, Control conditions: left, right, and sham rTMS) Action-object picture naming task (Center for Research in Language International Picture Naming Project)

  • Study made up of three experimental blocks: left, right, and sham rTMS stimulation

  • Improved action naming with right and left-sided rTMS
(Merrill et al., 2006) To evaluate the cognitive-enhancing effects of VNS in treating older adults with AD at one year. 17 (F=11) 63 (n/a) [57–81] AD, probable VNS Prospective pilot study (Participants: blind during 2 week surgical recovery period, Assessors: non-blind, Control conditions: none) ADAS-Cog, MMSE

  • 7/17 participants improved or did not decline as measured by ADAS-Cog after one year

  • 12/17 participants improved or did not decline as measured by MMSE after one year

  • No significant changes in median scores

  • No significant decline in mood, behaviour, or quality of life after one year

  • Most common adverse effect: voice alteration or hoarseness
(Katagai et al., 2007) To describe the clinical course of a patient with dementia with psychotic feature treated with ECT. 1 (F=1) 92 Dementia, cerebrovascular with psychotic feature ECT, bilateral (2 sessions) Case study Behave-AD

  • Experienced QTc prolongation while treated with haloperidol (0.5 mg, i.v.)

  • Almost all psychotic symptoms resolved after first session of ECT

  • No cognitive adverse effects observed
(Cotelli et al., 2008) To assess the effect of rTMS applied to the dorsolateral prefrontal cortex on picture naming in older adults with mild or moderate-severe AD. 24 (F=?) Mild AD: 75.0 (6.2), Moderate-severe AD: 77.6 (5.8) AD, probable rTMS (1 × 600 ms at 20 Hz) Experimental study (Participants: blind, Assessors: non-blind, Control conditions: left, right, and sham rTMS) Action-object picture naming task (Center for Research in Language International Picture Naming Project)

  • Study made up of three experimental blocks: left, right, and sham rTMS stimulation

  • Mild AD group (MMSE 17–30): improved action but not object naming with right and left-sided rTMS

  • Moderate-severe AD group (MMSE 0–16): improved action and object naming with right and left-sided rTMS
(Laxton et al., 2010) To investigate possible clinical benefits of DBS in older adults with AD by: 1) mapping brain areas whose physiological function are modulated by stimulation, (2) assessing whether DBS can correct regional alterations in cerebral glucose metabolism, and 3) measuring the effects of DBS on cognition over time. 6 (F=2) 60.7 (6.1) [51–69] AD, probable DBS Prospective pilot study (Participants: non-blind, Assessors: non-blind, Control conditions: none) ADAS-Cog, MMSE

  • Improvement or slowing in symptoms of AD as measured by ADAS-Cog and MMSE at 6 and 12-month follow-up post-DBS in some participants

  • PET scans showed reversal of impaired glucose metabolism in the temporal and parietal lobes; maintained after 12 months of DBS

  • No serious adverse events reported.
(Bentwich et al., 2011) To evaluate the efficacy of combination high-frequency repetitive TMS and cognitive training (rTMS-COG) in treating patients with AD. 8 (F=2) 75.4 (4.4) [69–80] AD, probable Intensive treatment (int-rTMS-COG): 5 sessions/wk for 6 wks. Maintenance (maint-rTMS-COG): 2 sessions/wk for 12 wks. Prospective pilot study (Participants: non-blind, Assessors: non-blind, Control conditions: none) ADAS-Cog, CGI, MMSE, ADAS-ADL, HDRS, NPI

  • ADAS-Cog scores improved by 4 points after both 6 weeks and 4.5 months

  • CGI scores improved by 1.0 after 6 weeks and 1.6 points after 4.5 months

  • MMSE, ADAS-ADL, and HDRS scores did not show statistically significant improvement

  • NPI test scores did not change

  • No adverse effects recorded
(Cotelli et al., 2011 To evaluate the long-term effect of rTMS applied to the left dorsolateral prefrontal cortex on cognitive performance in patients with AD. 10 (F=?) Real-real 71.2 (6.1); Sham-real 74.4 (3.8) AD, probable rTMS real-real (n=5), sham-real (n=5) (4 weeks, 5 sessions/wk) Prospective study (Participants: non-blind, Assessors: non-blind, Control conditions: sham-real treatment group) MMSE, Picture Naming Task, Battery for Analysis of Aphasic Deficits

  • Significantly improved auditory sentence comprehension in real-real group compared to the sham-real group and baseline

  • No adverse effects recorded
(Hausner et al., 2011) (also reported in Table 1) To study cognitive performance in depressed geriatric inpatients with or without pre-existing cognitive impairment who received a first course of ECT. 44 (F=33) 73 (6) [65–89] MDD with NCI (n=13), MCI (n=19), dementia (n=12) ECT, unilateral or bilateral (6 sessions) Prospective study (Participants: non-blind, Assessors: non-blind, Control conditions: none) HDRS

  • Remission of affective symptoms in all groups as measured by HDRS-21

  • Nonsignificant cognitive decline in all groups after initial ECT

  • Cognitive improvement in NCI and MCI groups 6 weeks and 6 months post-ECT

  • Cognitive improvement in participants withdementia on anti-dementia treatment after last ECT session; cognitive deterioration in participants with dementia not on anti-dementia treatment

  • Cognitive decline in 70% of dementia participants and 68.8% of MCI participants 6 weeks after last ECT session; decline remained in 33% of dementia participants 6 months after last ECT session
(Ujkaj et al., 2012) To evaluate the safety and efficacy of ECT for agitation and aggression associated with dementia. 16 (F=15) 66.6 (8.3) [51–79] AD (n=8), Vascular dementia (n=2), Frontotemporal dementia (n=3), Other dementia (n=3) ECT, unilateral then bilateral if insufficient response (9 sessions) [2–15] Retrospective systematic chart review Pittsburgh Agitation Scale, CGI, GAF

  • Significant decrease in agitation

  • 15/16 participants showed improvement

Alzheimer’s Disease (AD), Alzheimer’s Disease Assessment Scale-cognitive (ADAS-Cog), Alzheimer’s Disease Assessment Scale-activities of daily living (ADAS-ADL), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI), Deep Brain Stimulation (DBS), Electroconvulsive Therapy (ECT), Global Assessment of Functioning (GAF), Mini Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Vagus Nerve Stimulation (VNS)