Treatment of Alzheimer’s disease across the spectrum of severity

Figures & data

Table 1 Summary of major clinical trials of donepezil

Study	Sample size, n	Study duration	Baseline MMSE	Cognitive measures	Global measures
Rogers, Farlow, et al 1998	473	24 weeks	10–26	ADAS-cog, MMSE	CIBIC-Plus; CDR-SB
Rogers, Doody, et al 1998	468	12 weeks	10–26	ADAS-cog, MMSE	CIBIC-Plus; CDR-SB
Burns et al 1999	818	24 weeks	10–26	ADAS-cog	CIBIC-Plus, CDR-SB
Mohs et al 2001	431	1 year	12–20	MMSE	CDR, CDR-SB
Winblad et al 2001	286	1 year	10–26	GBS, MMSE	GDS
Feldman et al 2001	290	24 weeks	5–17	sMMSE	CIBIC-Plus

Abbreviations: ADAS-cog, Alzheimer’s disease assessment scale – cognitive subscale; CDR, clinical dementia rating; CDR-SB, clinical dementia rating – sum of the boxes; GBS, Gottfried-Brane-Steen scale; GDS, global deterioration scale; MMSE, mini-mental state exam; sMMSE, standardized mini-mental state exam; CIBIC-Plus, clinician interview-based impression of change incorporating caregiver information.

Table 2 Summary of major clinical trials of rivastigmine

Study	Sample size, n	Duration	Baseline MMSE	Cognitive measures	Global measures
Corey-Bloom et al 1998	699	26 weeks	10–6	ADAS-cog	CIBIC-Plus
Rosler et al 1999	725	26 weeks	10–26	ADAS-cog, MMSE	CIBIC-Plus
Farlow et al 2000	533	26 week open label extension of a 26 week placebo-controlled study	10–26	ADAS-cog	CIBIC-Plus
Burns et al 2004	112	Retrospective analysis from 3 trials	10–12	ADAS-cog, MMSE	PDS, BEHAVE-AD

Abbreviations: ADAS-cog, Alzheimer’s disease assessment scale – cognitive subscale; BEHAVE-AD: behavior pathology in AD rating scale; CIBIC-Plus, clinician interview-based impression of change incorporating caregiver information; MMSE, mini-mental state exam; PDS: progressive deterioration scale.

Table 3 Summary of major clinical trials of galantamine

Study	Sample size, n	Duration	Baseline MMSE	Cognitive measures	Global measures
Tariot et al 2000	978	5 months	10–22	ADAS-cog	CIBIC-Plus
Raskind et al 2000	636	6 months	11–24	ADAS-cog	CIBIC-Plus
Wilcock et al 2000	653	6 months	11–24	ADAS-cog	CIBIC-Plus
Lyketsos et al 2004	699	18.5 months (12 month open label extension of earlier 5 month study)	10–22	ADAS-cog	ADCS–ADL, NPI
Blesa et al 2003	72	12 months	<14 ADAS-cog	ADAS-cog	DAD
	165		>30

Abbreviations: ADAS-cog, Alzheimer’s disease assessment scale – cognitive subscale; ADCS–ADL, Alzheimer’s disease cooperative study – activities of daily living scale ; BEHAVE-AD: behavior pathology in AD rating scale; CIBIC-Plus, clinician interview-based impression of change incorporating caregiver information; DAD, disability assessment for dementia scale (Gelinas et al 1999); MMSE, mini-mental state exam; NPI, neuropsychiatric inventory (Cummings et al 1994).

Table 4 Summary of major clinical trials of memantine

Study	Sample size, n	Duration MMSE	Baseline	Dose	Outcome: last observation carried forward analyses at end point compared with placebo
Reisberg et al 2003	252	28 week	3–14	20 mg	SIB: −4.0 vs 10.1, p<0.001); CIBIC-Plus: 4.5 vs 4.8, p=0.06; ADCS-ADL: −3.1 vs −5.2, p=0.02
Tariot et al 2004 (patients already receiving donepezil for at least 6 months)	404	24 weeks	5–14	20 mg memantine/donepezil vs donepezil/placebo	SIB: 0.9 vs −2.5 p<0.001; CIBIC-Plus: 4.41 vs 4.66, p=0.03; ADCS-ADL: −3.4 vs −2.0, p=0.03
Winblad and Poritis 1999	166	12 weeks	<10	5 mg/day (first week) and 10 mg/day (next 11 weeks) vs placebo	CGI-C: (ITT): 73% positive response (memantine 10 mg/day) vs 45% (placebo). p<0.001; BGP: (ITT): 3.1 points improvement with memantine, 1.1 points with placebo. p=0.016)

Abbreviations: ADCS-ADL, Alzheimer’s disease cooperative study – activities of daily living scale ; CIBIC-Plus, clinician interview-based impression of change incorporating caregiver information; GCI-C, clinical global impression of change (NIMH 1986); BGP, behavioral rating scale for geriatric patients (van de Kam et al 1971); ITT, intent to treat analyses; SIB, severe impairment battery.

Table 5 Summary of antidepressant trials in elderly dementia patients

Study	Sample size, n	Study duration	Medication	Outcome
Pollock et al 2002	52	17 days	Citalopram (20 mg/day)	Agitation and lability significantly improved
Lyketsos et al 2003	44	12 week	Sertraline (mean dose 95 mg)	Significant improvement in depression but not in agitation
Finkel et al 2004	245	12 week	Sertraline (mean dose 125 mg)	No significant improvement in depression

Table 6 Overview of placebo-controlled trials of atypical antipsychotics in dementia

Study	Medication	Study design	Sample size, n	Duration	Outcome
Katz et al 1999	Risperidone, doses of 0.5 mg, 1.0 mg, 2.0 mg	Double-blind	625	12 week	Significant (>50%) reductions in some psychotic symptoms and aggression with Risperidone 1 mg
DeDeyn et al 1999	Risperidone (mean dose 1. 1 mg) or haloperidol (mean dose 1.2 mg), versus placebo	Double-blind	344	13 week	Risperidone caused >30% reduction in some measures of aggression
Street et al 2000	Olanzapine (doses of 5 mg, 10 mg, 15 mg daily) versus placebo	Double-blind	206	6 week	5 mg and 10 mg and not 15 mg had a significant decrease in agitation, aggression, hallucinations, delusions
Tariot et al 2002	Quetiapine (mean dose 120 mg), haloperidol (mean dose 2 mg)	Randomized placebo controlled		10 week	Both treatment groups improved in severity of psychosis and agitation. Quetiapine was better tolerated than haloperidol

Table 7 Commonly prescribed drugs, dosage guidelines in the elderly

Drug	Starting daily dose	Maximum recommended daily dose
Divalproex	125 mg twice daily	1000 mg
Carbamazepine	50–100 mg	500–800 mg
Risperidone	0.25–0.5 mg	1 mg
Olanzapine	2.5 mg	5–10 mg
Quetiapine	25 mg	200–300 mg
Trazodone	25 mg	100–150 mg
Buspirone	5 mg twice daily	30–45 mg
Lorazepam	0.5 mg	2 mg
Zolpidem	5 mg	10 mg

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