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Keywords:

  • alcohol;
  • Alzheimer's disease;
  • cholinergic system;
  • cognitive dysfunction;
  • dementia

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Background

Globally, Alzheimer's disease (AD) is becoming an increasing problem as the population ages, and the effects of lifestyle factors on cognitive decline need to be better understood. This study examined the effects of alcohol abstinence on cognitive decline in AD.

Methods

Cognitive function after alcohol abstinence was retrospectively reviewed in AD patients (high and low alcohol consumption groups) and then compared with an alcohol-naïve AD group. The alcohol-naïve AD group included 18 outpatients with no history of habitual drinking. The alcohol-abstinence AD group included 20 outpatients who stopped drinking after their diagnoses. The latter group was classified into high and low groups depending on the amount of they drank before abstinence. Cognitive function was evaluated with the Mini-Mental State Examination at baseline, 6 months, and 12 months. For statistical analyses, a repeated measures, two-factor anova and post-hoc multiple comparisons were performed using the Bonferroni method.

Results

There was a significant effect of time on Mini-Mental State Examination score, but there was no difference in the baseline scores of the alcohol-naïve and alcohol-abstinence AD groups. The score was significantly lower at 6 and 12 months than at baseline in the alcohol-naïve group, but no significant difference was seen in the alcohol-abstinence group. There was a significant interaction between time and alcohol consumption subgroup on the score, with no difference in baseline score between the low and high consumption groups. The score was significantly lower only in the high consumption group at 12 months.

Conclusions 

In AD patients with a history of habitual drinking, abstinence was effective for reducing cognitive decline during the clinical course. However, such an effect was not seen in patients who had consumed high amounts of alcohol before diagnosis of AD.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

In developed countries and throughout Asia, dementia has increased exponentially with the ageing of the population. Approximately 50%–60% of dementia cases have Alzheimer's disease (AD), which is considered the most common cause of age-related dementia in people 65 years of age or older.[1] Patients with certain medical risk factors, such as hypertension, atherosclerosis, high cholesterol, diabetes, and overweight or obesity in middle age, are more likely to develop AD.[2, 3] Lifestyle risk factors, such as alcohol drinking and smoking, have also been implicated in dementia.[4-7]

Many studies have examined the effects of alcoholism on cognitive function and the brain. Early studies of AD from the 1980s focused on the cholinergic system because it was known to play an important role in memory. Its role in AD was confirmed, and deficits in the cholinergic system in AD are now well established.[8] The cholinergic system is affected by alcohol use, and chronic alcohol use causes degeneration of cholinergic neurons.[9] Alcohol has been shown to decrease acetylcholine levels, reducing its synthesis and release. In addition, alcohol has extensive effects on neurotransmitter systems other than the cholinergic system and may also affect AD through these pathways.[10]

Epidemiologic studies have focused on whether people who drink alcohol have a greater or lesser chance of developing AD. Ruitenberg et al. reported that drinking a moderate or small amount of alcohol reduces the overall risk of dementia,[11] while Anttila et al. suggested that frequent drinkers had a higher overall risk of dementia than non-drinkers.[12] A number of studies overwhelmingly found that light to moderate drinking either reduced or had no effect on the risk of dementia.[8, 13] In particular, several studies have suggested that light to moderate intake of wine, which is rich in flavonoids, may be protective against dementia.[14, 15] In contrast, heavy drinking is associated with an increased risk of dementia.[13, 16] Many potential mechanisms have been suggested for interpreting the intricate relationship between alcohol consumption and cognitive function. Negative effects of heavy alcohol drinking on cognitive function have been attributed to alcohol-related nutritional deficiencies or the direct neurotoxic effects of ethanol.[17-19] Positive effects of light to moderate alcohol drinking on cognitive function have been attributed to flavonoids or other antioxidants contained in beverages, which may reduce the risk for dementia directly and indirectly.[15, 20]

Although many studies have investigated alcohol as a risk factor for developing AD, no studies have investigated the effects of abstinence from alcohol on cognitive function after the onset of AD. Therefore, in this study, the effect of abstinence from habitual drinking on the cognitive function of AD patients was investigated.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

The subjects of this study were recruited from the Department of Psychiatry, Juntendo University Hospital, Tokyo, Japan. All retrospectively analysed data were collected from medical records of routine clinical work; any sensitive information that could be attributed to specific individuals or groups of people were not recorded and reported here. All patients were diagnosed AD as either early-onset or late-onset AD, per the DSM-IV and National Institute of Neurological Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria.[21] All patients had typical findings on magnetic resonance imaging (general cortical atrophy including hippocampus) and single photon-emission computed tomography (reduced regional cerebral blood flow in the parietal lobe, posterior cingulate gyrus, and precuneus). The alcohol-naïve AD group consisted of 18 outpatients (15 early-onset, 3 late-onset; mean age 58.1 ± 8.3 years) with no history of habitual drinking. The alcohol-abstinence AD group included 20 outpatients (16 early-onset, 4 late-onset; mean age 60.0 ± 11.1 years) with a long history of habitual drinking who stopped after being diagnosed with AD (Table 1). According to Mukamal et al.,[22] the alcohol-abstinence AD group was categorized into the low (1–7 drinks/week) alcohol consumption group and the high (≥8 drinks/week) alcohol consumption group; 1 drink was defined as about 350 mL of beer. Almost half the patients began taking donepezil more than 3 months by home doctor's prescription. In such cases, a fixed dose donepezil 5 mg/day was continued; 5 mg/day is the approved dose in Japan for early- and middle-stage AD. Drug-naïve subjects with early-stage AD did not take medication throughout one year as they had no major troubles in ordinary daily living, they or their family did not want them to take it, or due to presence of gastrointestinal complaints that could be worsened by acetylcholinesterase-inhibitors.

Table 1. Clinical data
 Alcohol-naïve AD groupAlcohol-abstinence AD group
n = 18Total (n = 20)Low-group (n = 8)High-group (n = 12)
  1. AD, Alzheimer's disease.

Age, mean ± SD (year)58.1 ± 8.360.0 ± 11.157.1 ± 9.661.9 ± 12.1
Sex (men/women)11/717/35/312/0
Duration illness year, mean ± SD (year)1.8 ± 1.072.8 ± 2.42.7 ± 1.52.8 ± 2.9
Donepezil (fixed amount of 5 mg/day)101147
Donepezil-naïve8945

Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) at baseline, 6 months, and 12 months later.[23]

For statistical analyses, repeated measures, two-factor anova was used to examine differences in the MMSE score over time between the alcohol-naïve and alcohol-abstinence AD groups and between the low and high alcohol consumption groups. When significant differences were detected, post-hoc multiple comparisons were performed using the Bonferroni method. Statistical procedures were performed using SPSS v. 17.0 for Windows (Chicago, IL, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Table 1 show the clinical data of the alcohol-naïve and alcohol-abstinence AD groups, including the alcohol consumption subgroups. No differences in these data had a significant effect on the MMSE score by ancova (age, sex, duration illness year and drugs). Repeated measures, two-factor anova (3 times × group) revealed a significant main effect of time on MMSE score (F (2, 35) = 7.8, P < 0.05). There was no significant main effect of group on MMSE score.

There was no difference in the MMSE score at baseline between the alcohol-naïve and alcohol-abstinence groups. On the post-hoc multiple comparisons, the MMSE scores were significantly lower at 6 and 12 months than at baseline in the alcohol-naïve group while there were no significant differences in the alcohol-abstinence group (Fig. 1).

figure

Figure 1. Post-hoc multiple comparisons of Mini-Mental State Examination (MMSE) scores for the alcohol-naïve and alcohol-abstinence groups over time. AD, Alzheimer's disease; M, month.

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Repeated measures, two-factor anova (3 times × alcohol consumption subgroups) revealed a significant interaction of time and alcohol consumption subgroups on the MMSE score (F (1, 18) = 4.5 P < 0.05). There was no difference in the MMSE score at baseline between the low and high alcohol consumption groups. On the post-hoc multiple comparisons, the MMSE score was significantly lower at 12 months than at baseline only in the high alcohol consumption group; there was no significant difference in the low alcohol consumption group (Fig. 2).

figure

Figure 2. Post-hoc multiple comparisons of Mini-Mental State Examination (MMSE) scores for the high and low alcohol consumption groups over time. M, month.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

The effect of stopping habitual drinking on cognitive function in AD patients was examined. There were no differences in the baseline MMSE score between the alcohol-naïve and alcohol-abstinence groups. Nevertheless, only the alcohol-naïve group showed a decreased MMSE score at 6 and 12 months. The mean MMSE score decreased by 3.5 points from baseline to 12 months in the alcohol-naïve group. This decrease was considered to represent the typical change in the MMSE score seen after 1 year in AD patients.[24] In contrast, no decline in the MMSE score was observed in the alcohol-abstinence group.

It is of interest that previous studies have found that the cognitive function of alcoholics was reduced by heavy drinking and tended to improve with abstinence from alcohol.[25, 26] Improvement of cognitive function in alcoholics after abstention from alcohol suggests that their cognitive deficits may reflect neurochemical alterations rather than neuronal loss.[27] Alcohol-related memory loss can be partially reversed by compounds that stimulate the cholinergic system,[9] illustrating the importance of the cholinergic system in the effects of alcohol on memory.[8] Chronic alcohol use may aggravate the neurochemical alterations already present in AD, but this might be improved by abstinence.

It is also interesting that the presence of an apolipoprotein E allele, a history of heavy drinking, or a history of heavy smoking was each associated with an earlier onset of AD by 2–3 years.[14] Patients with all three risk factors were likely to be diagnosed with AD nearly 10 years earlier than those with none of the risk factors.[28] In the case of the alcohol-abstinence subgroups, the MMSE score of the high alcohol consumption group decreased 12 months after baseline, but the MMSE score of the low alcohol consumption group showed no change. The negative effects of heavy alcohol drinking on cognitive function could be attributed not only to cholinergic deficits but also to alcohol-related nutritional deficiencies or vascular changes in the brain.[17, 18] These forms of damage may be relatively irreversible even after abstinence from heavy drinking, and the effect of abstinence might therefore be relatively small in the heavy drinking group.

In the present study, none of the AD patients were vitamin deficient. Also, major magnetic resonance imaging findings did not suggest vascular changes. Although the heavy drinking group was comprised only of men, it is known that MMSE score is not affected by sex. The tendency in cognitive decline among the three AD groups was observed even when the data were analysed using only donepezil-naïve patients or only patients who had received donepezil. Therefore, although the findings of the heavy drinking group are not clearly explained, trying alcohol abstinence may be worthwhile in AD patients from a clinical viewpoint. The limitations of the present study are the relatively small number of AD patients involved, the exclusive use of MMSE assessment for cognitive function, and the 1-year follow-up.

Future research using a larger sample of patients is needed to elucidate other factors affecting cognitive decline in AD.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

None of the authors has any conflict of interest or received financial support for this study.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References