# Presentation: 432243

## GAL-INT-6 The safety and efficacy of galantamine in patients with Vascular dementia orAD with cerebrovascular disease Sean Lilienfeld MD, FCP, MMedJanssen Research Foundation

## Interactions between vascular dementia and Alzheimer’s disease

**AD**

- Mixed

- Erkinjuntti T

## Reminyl in vascular and mixed dementia: trial inclusion criteria

- 	Patients with dementia secondary to cerebrovascular disease (CVD) *with or without* AD
- _Probable_ Vascular dementia according to NINDS-AIREN criteria
- Mixed dementia according to NINCDS-ADRDA criteria of _possible_ Alzheimer’s disease with CVD and NINDS-AIREN criteria of _possible_ VaD
- MMSE at screening 10–25 and ADAS-Cog score at screening  12
- Positive radiology per NINDS-AIREN criteria

## Inclusion Criteria Probable Vascular Dementia (NINDS-AIREN)

- A. Dementia (decline from previous higher level of functioning):
- established by clinical examination and confirmed by neuropsychological test
- deficits in two or more areas of cognition
- no disturbance of consciousness, delirium, psychosis, severe aphasia, or major sensorimotor impairment precluding neuropsychological testing
- absence of systemic disorders or other brain diseases such as Alzheimer’s Disease (EXCEPT CEREBROVASCULAR DISEASE) that could account for the dementia

## Inclusion Criteria Probable Vascular Dementia (NINDS-AIREN)

- B.  Cerebrovascular disease:
- focal neurologic signs consistent with previous stroke (even with negative stroke history)
- evidence of relevant cerebrovascular disease by CT or MRI scan

## Inclusion Criteria Probable Vascular Dementia (NINDS-AIREN)

-  C.  A relationship must exist between the 	dementia and the cerebrovascular disease:
- onset of dementia within 3 months of a recognised stroke
- abrupt deterioration in cognitive functions
- fluctuating, stepwise progression of cognitive deficits

## Inclusion Criteria Mixed Dementia (Possible AD with CVD)

- NINCDS-ADRDA criteria for **possible **Alzheimer's disease and NINDS-AIREN criteria for possible Vascular Dementia
- Dementia established by clinical examination and confirmed by neuropsychological test
- Deficits in two or more areas of cognition
- Progressive worsening of memory and other cognitive functions no disturbance of consciousness
- Absence of systemic disorders or other brain diseases (EXCEPT  AD and CEREBROVASCULAR DISEASE) that could account for the dementia

## Inclusion Criteria Mixed Dementia (Possible AD with CVD)

- Radiologic evidence (satisfying the NINDS-AIREN radiologic criteria) as documented on a CT or MRI scan  less than 12 months old of:
- Multiple (2 or more) basal ganglion/white matter infarcts or lacunes and/or
- Single strategically placed infarct in angular gyrus/thalamus/basal forebrain/Anterior Cerebral Artery or Posterior Cerebral Artery territory and/or
- Extensive periventricular white matter lesions.

## Exclusion Criteria

- Other neurodegenerative disorders
- Other causes of cognitive impairment
- Relevant medical conditions eg. ulcers, bladder obstruction, severe hepatic, renal, pulmonary, cardiac diseases

## NINDS-AIREN Radiology

- multiple large-vessel infarcts
- single strategically placed infarct [angular gyrus, thalamus, basal forebrain, posterior or anterior cerebral artery territory]
- multiple basal ganglia and white matter lacunes
- extensive periventricular white matter lesions
- combinations of these

## Patient characteristics

- 		Placebo	Reminyl 24 mg/day
- 		(*n* = 196)	(*n* = 396)
- Female	46%	48%
- Mean age (years)	75.2	75.0
- Mean MMSE score	20.2	20.7
- Diagnosis
- 	Mixed dementia	50%	48%
- 	Vascular dementia	41%	43%
- 	Uncertain per MD	9%	9%

## ADAS-cog Scores: Placebo patients Over 6 Months

**-1**

**-2**

**Mean change ****+/- SE in ****ADAS-cog/11**

**Baseline**

**2**

**1**

**0**

**-3**

**Time (months)**

**Combined Placebo (n = 162)**

**1**

**2**

**3**

**4**

**6**

**5**

**Deteriorated**

**Treatment group**

**Improved**

**Mixed D Placebo (n = 87)**

**Probable VaD Placebo (n = 67)**

## ADAS-cog Scores: Placebo patients Over 6 Months

**1**

**-1**

**Baseline**

**3**

**2**

**0**

**-2**

**Time (months)**

**Mixed D Placebo (n = 87)**

**1**

**2**

**3**

**4**

**6**

**5**

**Deteriorated**

**Mean change ****+/- SE in ****ADAS-cog/11**

**Treatment group**

**Improved**

**Probable VaD Placebo (n = 67)**

****** ****= 2.2**
**p = 0.013**

## NPI Scores: Placebo patients Over 6 Months

**-1**

**Mean change ****(+/- SE) in ****total NPI**

**Baseline**

**2**

**1**

**0**

**-2**

**Time (months)**

**Placebo **

**1**

**2**

**3**

**4**

**6**

**5**

**Deteriorated**

**Treatment group**

**Improved**

**Probable VaD Placebo**

**Mixed D Placebo**

## NPI Scores: Placebo patients Over 6 Months

**-1**

**Mean change ****(+/- SE) in ****total NPI**

**Baseline**

**2**

**1**

**0**

**-2**

**Time (months)**

**1**

**2**

**3**

**4**

**6**

**5**

**Deteriorated**

**Treatment group**

**Improved**

**Probable VaD Placebo**

**Mixed D Placebo**

****** ****= 0.4**
**p = 0.43**

## DAD Scores: Placebo patients Over 6 Months

**-1**

**-4**

**Baseline**

**2**

**1**

**0**

**-6**

**Time (months)**

**Placebo **

**1**

**2**

**3**

**4**

**6**

**5**

**Improved**

**Mean change ****(+/- SE) in ****total DAD**

**Treatment group**

**-2**

**-3**

**-5**

**Deteriorated**

**Mixed D Placebo**

**Probable VaD Placebo**

## DAD Scores: Placebo patients Over 6 Months

**-1**

**-4**

**Baseline**

**1**

**0**

**-8**

**Time (months)**

**Mixed D Placebo **

**1**

**2**

**3**

**4**

**6**

**5**

**Improved**

**Mean change ****(+/- SE) in ****total DAD**

**Treatment group**

**-2**

**-3**

**-7**

**-6**

**-5**

**Deteriorated**

**Probable VaD Placebo**

****** ****= 4.7**
**p = 0.032**

## Efficacy results

- ADAS-cog positive
- CIBIC-plus positive
- NPI positive
- DAD positive

## Conclusions

- Using NINDS-AIREN criteria physicians were able to differentiate patients with “probable” vascular dementia and “mixed” dementia
- Observed rates of deterioration in a cognitive scale, a neuropsychiatric scale and a functional scale,  are different in the 2 placebo groups, thus these patients are indeed different clinical populations

## Conclusions

- Patients with “mixed” dementia deteriorate at rates similar to those seen in clinical trials in patients with probable AD over 6 months whereas patients with probable VaD remain essentially at baseline over 6 months

## Galantamine Significantly Improved Both Primary Endpoints and Both Secondary Endpoints

- The current efficacy tools are able to detect differences between actively treated and placebo treated patients with a magnitude similar to that seen in trials in patients with AD