**6. Treatment of mild cognitive impairment**

The aim of MCI treatment is to reduce existing clinical symptoms or to delay progression of cognitive dysfunction and prevent dementia. Unfortunately, at present there is no effective pharmacological therapy of mild cognitive impairment. Clinical trials on the effectiveness of Cholinesterase inhibitors didn't prove that they can delay the onset of Alzheimer's disease (AD) or dementia in individuals with MCI. Cooper et al. performed systemic review of studies on MCI treatment. They summarized results of 9 clinical trials on Cholinesterase inhibitors. Reduction in incidence of Alzheimer's disease has not been proven with 4 high quality trials (two evaluated galantamine, one donepezil and one rivastigmine). In one of the trials donepezil and galantamine showed improvement in global cognitive functioning. However, global cognition did not improve in other five large trials of Cholinesterase inhibitors. Donepezil improved immediate memory and delayed progression to AD in MCI patients with depression without affecting their symptoms of depression [38].

In a 2-year, double-blinded, placebo-controlled study, 232 MCI patients were administered 16 mg. galantamine combined with 20 mg. memantine, galantamine only, or a placebo. The amnestic MCI subgroup in the treatment arm combining galantamine and memantine demonstrated a significant positive effect on cognition. Discontinuation of galantamine, but not memantine led to a decline in cognitive functioning [38].

Ginkgo biloba is a natural medicine widely used to enhance memory. Yang et al. conducted meta-analysis of randomized clinical trials on Ginkgo biloba in treating mild cognitive impairment or Alzheimer's disease. Data from 21 trials with 2608 patients have been analyzed [39]. Compared with conventional medicine alone, Ginkgo biloba in combination with conventional medicine was superior in improving Mini-Mental State Examination (MMSE) scores for patients with Alzheimer's disease and mild cognitive impairment. When compared with placebo or conventional medicine in individual trials, Ginkgo biloba demonstrated similar but inconsistent findings. Adverse events were mild.

Study by Delano-Wood et al. showed that diminished white matter integrity of PC was strongly predictive of MCI status. Additionally, patients with amnestic MCI demonstrated lower PC

FDG-PET ([18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography) studies have found substantial reduction in brain activity in some cortical regions (HC limbic system, medial thalamus, and posterior cingulate). These findings are consistent with structural MRI findings [5, 37]. SPECT studies have reported reduced cerebral blood flow (CBF) in the parietal cortex, posterior cingulated cortex and precuneus in persons with MCI. Longitudinal SPECT studies showed that the presence of AD-like hypoperfusion in the posterior posterior cingulate cortex

Accumulation of amyloid-β (Aβ) fibrils in the form of amyloid plaques is a neuropathological hallmark of dementia caused by AD. Amyloid deposition appears an early event in AD, possibly occurring up to 20 years before clinical symptoms. Amyloid imaging has become one of the central biomarkers of AD and predictor of cognitive decline. There is evidence that a positive amyloid PET scan result in patients with MCI will help in predicting conversion to AD. Amyloid-PET may help to differentiate between different etiologies of cognitive dysfunction and in the future it may help to appropriately select patients for anti-amyloid therapy [5].

The aim of MCI treatment is to reduce existing clinical symptoms or to delay progression of cognitive dysfunction and prevent dementia. Unfortunately, at present there is no effective pharmacological therapy of mild cognitive impairment. Clinical trials on the effectiveness of Cholinesterase inhibitors didn't prove that they can delay the onset of Alzheimer's disease (AD) or dementia in individuals with MCI. Cooper et al. performed systemic review of studies on MCI treatment. They summarized results of 9 clinical trials on Cholinesterase inhibitors. Reduction in incidence of Alzheimer's disease has not been proven with 4 high quality trials (two evaluated galantamine, one donepezil and one rivastigmine). In one of the trials donepezil and galantamine showed improvement in global cognitive functioning. However, global cognition did not improve in other five large trials of Cholinesterase inhibitors. Donepezil improved immediate memory and delayed progression to AD in MCI patients with depres-

In a 2-year, double-blinded, placebo-controlled study, 232 MCI patients were administered 16 mg. galantamine combined with 20 mg. memantine, galantamine only, or a placebo. The amnestic MCI subgroup in the treatment arm combining galantamine and memantine demonstrated a significant positive effect on cognition. Discontinuation of galantamine, but not

Ginkgo biloba is a natural medicine widely used to enhance memory. Yang et al. conducted meta-analysis of randomized clinical trials on Ginkgo biloba in treating mild cognitive impairment or Alzheimer's disease. Data from 21 trials with 2608 patients have been analyzed [39].

white matter integrity relative to those with non-amnestic MCI [5, 34].

of patients in MCI was predictive of conversion to AD [37].

100 Alzheimer's Disease - The 21st Century Challenge

**6. Treatment of mild cognitive impairment**

sion without affecting their symptoms of depression [38].

memantine led to a decline in cognitive functioning [38].

The Ginkgo Evaluation of Memory (GEM Study) study was a randomized, double-blind placebo-controlled multicenter trial, which was held in 2000–2008 years in the United States. Out of 3069 participants of the clinical trial, most of them (n=2587) didn't have cognitive dysfunction, and 15.7% (n=482) were diagnosed with mild cognitive impairment on the basis of Peterson's criteria. After completion of the 6 -year observation period no significant effect of Ginkgo biloba on the incidence of dementia could be demonstrated [40].

There is an evidence, that inflammation plays an important role in the pathophysiology of Alzheimer's disease. Several epidemiological studies showed negative association between usage of anti-inflammatory nonsteroidal medications and development of Alzheimer's disease. For example, the Canadian Study of Health and Aging involving 5276 cognitively normal subjects demonstrated that there is an association between NSAID use and a lower incidence of AD and cognitive impairment no dementia (CIND) [38].

One large multicenter study on the efficacy of the COX-II inhibitor in preventing dementia has been conducted. In the trial participated 1457 subjects with mild cognitive impairment, half of them were taking Rofecoxib, approximately for 4 years. Trial revealed significantly high frequency of Alzheimer's disease in the group that used Rofecoxib [38].

A randomized, double-blind, placebo-controlled trial of Triflusal in patients with amnestic mild cognitive impairment reported no significant effect of Triflusal treatment on cognition, although it was associated with a reduced risk of conversion to AD [38].

Centrally acting angiotensin-converting enzyme inhibitors (CACE-Is) have demonstrated positive effect on cognitive function in a study including 361 patients with AD, vascular dementia, or mixed dementias, regardless of blood pressure levels at the time of their hypertension diagnosis.

Piridebil is an antagonist of dopamine receptors. Based on experimental trials it increases acetylcholine release in hippocampus and frontal cortex. Piribedil improved cognition over 3 months in individuals with MMSE of 21–25, in one small placebo controlled study.

The role of B vitamins was studied in few clinical trials. However, the data does not yet provide adequate evidence of an effect of vitamins B on general cognitive function, executive function and attention in people with MCI. Similarly, B vitamins are unable to stabilize or slow decline in cognition, function, behavior, and global change of AD patients.

Twelve-week treatment with dietary supplementation containing an oily emulsion of docosahexaenoic acid (DHA)-phospholipids demonstrated considerable improvement in cognitive function in 25 elderly patients with MCI in a randomized controlled study. Studies support the effectiveness of omega 3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on cognitive function, depressive symptoms and general functioning in persons with MCI [41].

Cochrane review on the use of vitamin E in the treatment of mild cognitive impairment and AD did not identify evidences that alpha-tocopherol prevents MCI progression or that it improves cognitive function in people with MCI due to AD. However, there is moderate quality evidence from a single study that it may slow functional decline in AD [42].

Other meta-analyses of long-term (5–10 years) studies reported lower annual conversion rates of 3.3–4.2% and cumulative conversion rate ~31% over 10 years. In fact, a substantial percentage of individuals with MCI actually revert to normal. Sujuan et al. found that the annual reversion rate from MCI to normal cognition was substantially higher (18.6%) than the annual progression rate from MCI to dementia (5.6%) in a study spanning between 1992

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http://dx.doi.org/10.5772/intechopen.75509

Studies suggest that common factors related to MCI reversion include genetics (i.e., fewer APOE ε4 alleles), preserved global functioning, subtype of MCI (i.e., non-amnestic single domain), cognitive functioning (i.e., higher standard scores on cognitive assessments), and neuroimaging (i.e., larger hippocampal volumes) [45]. Huey et al. found that single-domain executive MCI has a better outcome than amnestic MCI and that executive dysfunction in multiple-domain MCI

It has been shown that as many as 30% of people with MCI have potentially treatable causes of cognitive decline. The most common of these include hypothyroidism, vitamin B12 deficiency, vascular disease, normal pressure hydrocephalus, and subdural hematoma. Another study concluded that changing the risk factors for stroke and treating depression may have

Nevertheless, the proportion of patients with MCI who convert to dementia still remains significant and it is important to identify factors that facilitate progression for adequate prevention and application of both pharmacological and non-pharmacological therapies. Adequate and on timely identification of MCI in definite cases can help to plan effective strategies for prevention

We would like to thank Dr. Nina Mikeladze and Dr. Natalia Chlikadze for their contribution

\*

does not independently increase the risk of progression to dementia [46].

contributed MCI reversion to normal [47].

of progressive cognitive decline.

to the revision and translation process.

We have no conflict of interest to declare.

Marina Janelidze1,2 and Nazibrola Botchorishvili1

1 Tbilisi State Medical University, Tbilisi, Georgia

\*Address all correspondence to: nbphosta@gmail.com

2 Simon Khechinashvili University Hospital, Georgia

**Acknowledgements**

**Conflict of interest**

**Author details**

and 2009 [44].

Meta-analysis of prospective trials revealed, that Mediterranean diet reduces risks of development of Alzheimer's disease and also progression of mild cognitive impairment into dementia. Mediterranean diet could potentially exert neuroprotective effects via different mechanisms, such as reduction of inflammation and oxidative stress.

Non pharmacological treatment of MCI involves management of modifying risk factors, social and cognitive rehabilitation and physical activity.

There is growing evidence that cognitive interventions may be associated with small cognitive benefits for patients with MCI and dementia. Based on recent trials, computer training program has particular positive effect on cognition and mood. Cooper at al. reviewed two long term group psychological intervention studies. They found that 20 sessions of memory training, reminiscence, cognitive stimulation, psychomotor recreation and social interaction improved global cognition on a primary outcome in a single, very small, 6-month placebo-controlled trial. However, another trial including ten sessions of memory training, psycho education and relaxation did not improve recall on secondary outcomes in one small 6-month trial [38].

Mayo clinic professionals created a MCI intervention program called Healthy Action to Benefit Independence and Thinking (HABIT). HABIT is a 10-day (50 hours) multi-component program offered to individuals with mild cognitive impairment. The program builds on existing strengths and recognizes that procedural memory can be utilized to promote the highest level of function and independence. The program includes five essential components: Individual memory compensation training; Group supportive therapy; Yoga; Brain fitness; Wellness education. Preliminary program evaluation data suggests positive impact on self-efficacy outcomes for patients and caregivers, as well as positive impact on patient functional outcomes [43].

Exercise has been associated with positive effects on neuronal survivability and function, neuroinflammation, vascularization, neuroendocrine response to stress, and brain amyloid burden. It also helps to improve cardiovascular risk factors. Ohman et al performed systematic review of selected 22 trials examining the effect of physical exercise on cognitive performance. According to the review of studies on older subjects with MCI reported some positive effect of physical exercise on cognition, mainly on global cognition, executive function, attention and delayed recall. However, most studies performed in older subjects with dementia showed no effect of exercise on cognition [39].
