Table 1.

Characteristics of Included studies of pharmacological treatments (donepezil, galantamine, and memantine) for dementia severity and global function.

Study	Sample and setting	Outcomes	Treatment	Follow-up time points
Black 2007	n = 343 (F=241; M=102) Mean age: 78.0; Mean MMSE: 7.45 Diagnosis: AD	Primary outcomes 1.SIB 2.CIBIC-Plus Secondary outcomes 3.MMSE 4.ADCS-ADL-sev 5.NPI 6.CBQ 7.RUSP	Donepezil 10 mg/day (n=176) Placebo (n=167)	-8, 16, and 24 weeks (primary endpoint)
	Inclusion criteria:
	1.MMSE ≤ 12 2.FAST ≥ 6 3.Modified HIS ≤ 6 4.Carer with contact ≥ 4 hours per day
	Definition of severe dementia: MMSE ≤ 12 and FAST score ≥ 6
	Community
	-98 centers in USA, Canada, France, UK, & Australia
Burns 2009 (SERAD study)	n = 407 (F=329; M=78) Mean age: 83.6; Mean MMSE: 8.95 Diagnosis: AD and AD with CVD	Primary outcomes 1.SIB 2.MDS-ADL (7 items) Secondary outcomes 3.Sub items of SIB 4.MDS-ADL (11-items)	Galantamine 24 mg/day (n=207) Placebo (n=200)	-8, 12, and 26 weeks (primary endpoint)
	Inclusion criteria:
	1.MMSE 5-12 2.History of cognitive decline 3.CT/MRI scan 3 years before enrolment 4.Sufficient vision & hearing 5.Resident for ≥ 6 months
	Definition of severe dementia: MMSE 5-12
	57 Nursing homes
	-10 European countries
Feldman 2005 (MSAD study)	n = 145 (F=86; M=59) Mean age: 73; Mean MMSE: 8.94 Diagnosis: AD	Primary outcomes 1.CIBIC-Plus Secondary outcomes 2.sMMSE 3.SIB 4.DAD 5.IADL 6.PSMS 7.NPI	Donepezil 10 mg/day (n = 72) Placebo (n = 73)	-4, 8, 12, 18, and 24 weeks (primary endpoint)
	Inclusion criteria:
	1.FAST ≥ 6 2.MMSE 5-12 3.Available carer
	Definition of severe dementia: sMMSE 5-12
	Community/assisted living facilities
	-Canada, Australia, & France
Hannestad 2021	n = 26 (F=16; M=10) Mean age= 73.5; Mean MMSE: 5.4 Diagnosis: AD Inclusion criteria: 1.Aged 65-90 years 2.MMSE ≤ 10	Primary outcomes 1.MMSE 2.SIB 3.ADCS-ADL-sev 4.NPI	GRF6019 intravenous infusions of 250 mL IV over 5 days (n=18) Placebo (n=8)	-9 weeks (primary endpoint)
	Definition of severe dementia: MMSE 0 -10
	Community and 4 nursing homes/ long-term care facilities
	-United States
Homma 2008b	n = 302 (F=245; M=57) Mean age: 78.2; Mean MMSE: 7.76 Diagnosis: AD	Primary outcomes 1.SIB 2.CIBIC-Plus Secondary outcomes 3.ADCS-ADL-sev 4.BEHAVE-AD	Donepezil 5 mg/day (n = 101) Donepezil 10 mg/day (n =96) Placebo (n = 105)	-24 weeks (primary endpoint)
	Inclusion criteria:
	1.Aged ≥ 50 years 2.HIS ≤ 6 3.FAST ≥ 6 4.MMSE 1-12
	Definition of severe dementia: MMSE 1-12 and FAST score ≥ 6
	Community
	-Japan
Jia 2017	n = 313 (F=266; M=110) Mean age: 70.8; Mean MMSE: 7.3 Diagnosis: AD	Primary outcomes 1.SIB Secondary outcomes 2.CIBIC-Plus 3.MMSE	Donepezil 10 mg/day (n=157) Placebo (n=156)	-24 weeks (primary endpoint)
	Inclusion criteria:
	1.Aged 50-90 years 2.SIB 10 – 90 3.MMSE 1-12 4.Carer with contact ≥ 4 hours per day
	Definition of severe dementia: MMSE 1-12 and SIB scores of 10 – 90
	Hospitals
	-China
Reisberg 2003ª	n = 252 (F=170; M=82) Mean age: 76.1; Mean MMSE: 7.9 Diagnosis: AD	Primary outcomes 1.GCI-C 2.ADCS-ADLsev Secondary outcomes 3.SIB 4.MMSE 5.FAST 6.GDS 7.NPI	Memantine 20mg (n=126) Placebo (n=126)	-12, and 28 weeks (primary endpoint)
	Inclusion criteria:
	1.Aged ≥ 50 years 2.GDS 5 or 6 3.MMSE 3-14 4.FAST ≥ 6
	Definition of severe dementia: MMSE 1-10
	Community
	-32 centers, USA
Winblad 1999	n = 166 (F=96; M=70) Mean age: 68.4; Mean MMSE: 6.3 Diagnosis: Dementia (not further specified)	Primary outcomes 1.GCI-C 2.BGP Secondary outcomes 3.Ferm’s D-test	Memantine 10mg (n=82) Placebo (n=84)	-12 weeks (primary endpoint)
	Inclusion criteria:
	1.Aged 60-80 years 2.GDS 5-7 3.MMSE <10 4.Dementia duration > 12 months
	Definition of severe dementia: MMSE <10 and GDS score 5-7
	1 psychiatric hospital and 6 nursing homes
	-Latvia
Winblad 2006	n = 248 (F=190; M=58) Mean age: 84.9; Mean MMSE: 6.1 Diagnosis: AD	Primary outcomes 1.SIB 2.ADCS-ADL-sev Secondary outcomes 3.GCI-C 4.MMSE 5.NPI	Donepezil 10 mg/day (n=128) Placebo (n=120)	-12, and 24 weeks (primary endpoint)
	Inclusion criteria:
	1.Aged ≥ 50 years 2.Ability to walk alone 3.FAST 5-7c 4.MMSE 1-10
	Definition of severe dementia: MMSE 1 -10 and FAST score 5-7c
	50 nursing homes
	-Sweden

Note: MMSE: Mini-Mental State Examination; FAST: Functional Assessment Staging; HIS: Hachinski Ischemic Score; SIB: Severe Impairment Battery; CIBIC-Plus: Clinician’s Interview-Based Impression of Change-Plus; ADCS-ADL-sev: Alzheimer's Disease Cooperative Study-Activities of Daily Living inventory modified for Severe Patients; NPI: Neuropsychiatric Inventory; CBQ: Caregiver Burden Questionnaire; RUSP: Resources Utilisation for Severe Alzheimer's Disease; CVD: Cerebrovascular disease; MDS-ADL: Minimum Data Set Activities of Daily Living; sMMSE: Severe Mini-Mental State Examination; DAD: Disability Assessment for Dementia; IADL: Instrumental Activities of Daily Living; PSMS: Physical Self-Maintenance Scale; BEHAVE-AD: Behavioral pathology in Alzheimer's disease; GDS: Global Deterioration Scale; GCI-C: Clinical Global Impression of Change; BGP: Behavioral Rating Scale for Geriatric Patients

ªData in people with severe dementia are reported but are not extractable from the primary paper

^bData extracted were based on the safety population as reported in the original paper