In Alzheimer’s disease patients with cerebrovascular disease …How can you expect to keep up with the acceleration in advanced biomedical discoveries in 2017 (and beyond) if you don’t improve your ability to concentrate and enhance your powers of attention?
Without these enhancements, your chances of staying healthy (and perhaps even staying alive) greatly diminish.
We now know that it is possible to increase the effects of an acetylcholinesterase inhibitor(AChEI) such as galantamine with the addition of choline alphoscerate. Other choline donors such as citicoline and choline (as in choline citrate) are also thought to improve the power of galantamine [See sidebar, “Combined Administration of AChEIs and Choline Donors.”] Galantamine and choline are good for concentration and attention, especially when taken together. Thus, disturbances of memory and attention in Alzheimer’s disease (AD) and other memory disorders can be improved (see “Enhancing the Power of Galantamine” in the September 2016 issue).
Investigating Attention Deficits
Impaired attention is one of the cognitive deficits detected in the early stages of AD. Degraded attention diminishes the ability to socially interact with other people1 and severely impairs specific skills, such as driving.2 This deficit can also increase the caregivers’ burden.1
Some of the other attentional impairments seen in AD can be ascribed to an alteration of the basal forebrain cholinergic system, in particular the nucleus basalis of Meynert(see Fig. 1), which undergoes significant neuronal loss in AD.3 The basal forebrain cholinergic system provides the cholinergic innervation to the thalamus, prefrontal cortex and parietal lobes, all structures known to be involved in attentional operations.
AD Patients with CVD Study
The aim of a new study was to investigate the effect of galantamine on attention in Korean AD patients with CVD.4 In this open trial, 1512 patients with AD and CVD were recruited from 71 nationwide hospitals between July 2008 and May 2009. The patients were given galantamine for 16 weeks. The primary outcome result was the score on the Attention Questionnaire Scale (AQS), which measures the patients’ attention in their daily lives. In this result, scores can range from 0 (severe attention deficit) to 30 (no attention deficit). The secondary outcome measures were the scores on the Korean Mini-Mental State Examination, the Clinical Dementia Rating (CDR) scale and the Global Deterioration Scale (GDS). Efficacy measures were calculated both at the beginning (baseline) and at the end of the treatment, which lasted 16 weeks.
The debilitating memory disruptions
The responders’ rate on the AQS (change of the AQS from baseline >0) was 60.6% in AD patients with CVD. At the end of the treatment, both the AQS (15.0 ± 5.7 vs 16.3 ± 5.8) and the Korean Mini-Mental State Examination scores (17.8 ± 4.8 vs 18.1 ± 5.1) showed a significant improvement relative to the baseline performance.
The Clinical Dementia Rating (1.25 ± 0.59 vs 1.22 ± 0.63) and Global Deterioration Scale (3.82 ± 0.94 vs 3.76 ± 0.96) scores also showed a significant decrease at the end of the treatment.
According to the researchers’ best knowledge, no study to date has examined the effect of a AChEI (such as galantamine) on attention in AD patients with CVD. Recently, a brief informant-based Attention Questionnaire Scale (AQS) was developed, under the premise that a patient’s attention in everyday life might reflect real-life situations much better than the artificial laboratory attention tasks. The AQS significantly correlated with attention tasks. The AQS might also be useful in a “real-world” clinical setting without a neuropsychometrician or in a brief evaluation of attention in a study carried out in several clinics.
The aim of the present study was to investigate the effect of galantamine on attention measured with the AQS in AD patients with CVD. The patients were aged 50–85 years, and had a Korean Mini-Mental State Examination (K-MMSE) score between 10 and 25. They were also in the care of a caregiver who was able to provide the investigator with the information necessary to complete the study. The AQS includes eight negative items (e.g. “Does he/she easily become inattentive?”) and seven positive items (e.g. “Is he/she good at concentrating on one thing?”). Each item was rated on a three-point scale (0 = none or never, 1 = intermediate or sometimes, 2 = many or always). The total score was calculated by tallying up the score of responses that would suggest probable attention deficits (– negative item score + positive item score). Scores can range from 0 (severe attention deficit) to 30 (no attention deficit).
A total of 1512 patients were enrolled and took at least one dose of galantamine. Among these, 365 patients (24.1 %) dropped out. The safety population comprised 1512 patients, and the per-protocol population for efficacy evaluation comprised 1147 patients. There were no significant differences in age, sex and K-MMSE score at baseline between the subjects who discontinued the study and those who completed it. At the end of the treatment, 574 (38.0%), 697 (46.1 %) and 241 (15.9%) patients were receiving 8 mg, 16 mg and 24 mg of galantamine, respectively. The average daily dose of galantamine was 14.2 ± 5.6 mg.
The responder rate of the AQS (change of the AQS from baseline > 0) was 60.6% in AD patients with CVD. The responder rate in AD patients with CVD from the present study was within the 95% CI (54.7–60.7%) of the responder rate of the AQS in 1393 patients having AD without CVD at week 16 after taking galantamine from our previous study (unpubl. data).
The patients showed a significant increment in the AQS at week 16, compared with the baseline score (15.0 ± 5.7 vs 16.3 ± 5.8). In the previous study (unpubl. data), 1393 patients having AD without CVD also showed a significant increment in the AQS at week 16 after taking galantamine, compared with the baseline score (14.9 ± 5.7 vs 16.0 ± 5.8). They also had a significant increment in K-MMSE, and significant decrements in Clinical Dementia Rating and Global Deterioration Scale at week 16 compared with the baseline scores.
Overall, the results show that galantamine is associated with improvement of attention on the AQS in AD with CVD. Galantamine is effective in improving attention in the daily lives of AD patients with CVD. Galantamine might be more beneficial in AD patients with CVD, because they have greater attentional deficits compared with AD.