aging leads to senile diseases , including alzheimer disease ( ad ) , which has become a serious medical and socioeconomic problem .
therefore , progress in early diagnosis and effective treatment of ad is necessary , especially in the preliminary or early stages of the disease .
most elderly people experience physiological memory disorders ; these disorders require a careful clinical assessment , as it is extremely difficult to delineate the line between physiology and pathology .
thus , when disorders of memory and other cognitive functions go beyond the standards of age and educational level , but have not yet reached the standards of dementia , we diagnose mild cognitive impairment ( mci ) , which includes several states that either match the standard in its wide meaning , for example age - associated memory impairment ( aami ) , age - related cognitive decline ( arcd ) , or we diagnose pathology like mci , which , although clinically similar , has a different prognosis than aami and arcd [ 14 ] . currently , base on criteria established by the mayo clinic group , mci is define as a transitional state between normal aging and alzheimer s disease , in which memory impairment is greater than expected for age , but general cognitive function and daily living activities are preserved .
people suffering from mci , especially amnestic form ( amci ) , are at risk for developing dementia , particularly alzheimer disease ( ad ) [ 35 ] . according to various reports
, the percentage of conversion from amci into ad ranges from 1% to 25% per year , while the mean time of dementia progression from the mci diagnosis is 4.4 years . obviously , the early identification of patients at risk for alzheimer disease from among those with mci would facilitate proper treatment help to delay the symptoms of dementia .
therefore , searching for methods that would help us detect a higher risk of dementia in those patients , as well as looking for objective methods of early diagnosis of patients with mci , seems reasonable .
many reports confirm a typical repeatable topographical location of neuropathological lesions at various stages of ad , as described by braak et al and pantel et al . , while emphasizing early involvement of the limbic system , including the hippocampus and entorhinal cortex .
earlier pathology in these strategic regions in patients with a higher risk of alzheimer - type dementia , as well as in certain patients with amnestic mci , seems likely .
atrophy of the medial temporal lobe in mci patients with a positive correlation of atrophy level and a risk of conversion to ad , inadequate for age and observed in imaging examinations ( ct , mri ) , has been clearly demonstrated [ 813 ] .
the level of atrophy is judged by descriptive , volumetric and planimetric methods , or indirectly with the use of linear measurements of particular fluid spaces , such as fissures or certain parts of the ventricular system . despite many years of experience in structural diagnosis of the dementia diseases
, the use of functional methods seems to be very helpful . in spect and pet examinations
we observe the lowering of perfusion and metabolism of glucose and oxygen in temporal and parietal areas in patients with possible ad , as well as in those with mci .
however , these methods have certain limitations such as relatively low linear resolution , which hinders precise determination of the topography of the measuring ( this problem relates to the middle temporal structures and not to the hemispheres cortex ) . a wider clinical application of magnetic resonance spectroscopy ( mrs ) , described by bootomley as  a window for metabolism
   enabled an intravital assessment of regional metabolic disorders in certain structures of the brain .
there have been several reports on such dysfunctions in the limbic system in patients with alzheimer disease .
a relatively small number of spectroscopic examinations have been carried out on patients with mci .
some of these were presented by catani et al . , who located voxels in the white matter at the ventricular triangle level   and kantarci et al .   who examined the posterior part of the cingulate gyrus in patients with mci and ad . however , these are the locations where anatomopathologic changes , typical for ad , appear later than in the medial temporal lobe ( including hippocampal formation ) .
many authors give up on spectroscopic examinations of hippocampal structures due to their technical limitations , such as the size of examined structures and topographical relations of the surrounding area .
the problems mentioned most often are : difficulties with field homogeneity , artifacts from cranial base area , a disqualifying weakening of the signal - to - noise ratio , and the need to reduce the volume of interest ( voi ) .
there have been reports on the technical capacities of such examinations in various brain diseases [ 1923 ] . according to available the available literature , in the majority of papers h1mrs in mci and ad metabolites were measured in the posterior cingulated gyrus , but parts of papers evaluated the concentration of metabolites in the bilateral hippocampi of mci patients .
this study attempted to evaluate the regional metabolic disorders using h mrs within the frontal , external and medial temporal lobes in patients with mci , as a predictor of clinical deterioration to dementia based on clinical follow - up .
this study attempted to evaluate the regional metabolic disorders using h mrs within the frontal , external and medial temporal lobes in patients with mci , as a predictor of clinical deterioration to dementia based on clinical follow - up .
the examination was performed on a group of 31 randomly selected subjects ( 19 females and 12 males ) with mci diagnosed under the care of the department of neurodegenerative disorders , medical research centre , polish academy of science .
all subjects underwent neurological and psychiatric tests , routine laboratory investigations and standard neuropsychological examinations .
patients with serious cns injuries , alcoholic abuse , diabetes , and serious hepatic and renal dysfunctions were excluded .
mci diagnosis was established by a team of specialists after analyzing all available information and test results .
mri and h mrs examination was performed on a 1.5 t eclipse ( marconi medical systems , usa ) scanner .
morphological mri examination of the brain was carried out in transverse planes , parallel to the longitudinal axis of the temporal lobe in se , fse and flair sequences , in t1- and t2-weighted images , and in the frontal plane perpendicular to the longitudinal axis of the temporal lobe in flair sequence .
we investigated the extent of cerebral atrophy , especially in medial and external temporal lobes and in frontal structures , as well as the presence of cortical - subcortical hyperintensive focuses ( which equal angiogenic lesions ) in t2-weighted images and flair sequence .
morphological examination enabled us to exclude other pathologies such as extensive ischemic lesions , tumors , paracerebral hematomas , and hydrocephalus , which might lead to cognitive disorders .
changes like leukoaraiosis and/or small single angiogenic focuses of gliosis were not exclusion criteria for the study .
the voi ( volume of interest ) was located in the frontal , medial and external temporal lobe regions , separately on each side . in case of medial temporal lobe covering the hippocampal formation ,
it was divided into 2 areas  the anterior ( the topographical point of reference in the coronal plane / layer was the level of dens ) and the posterior ( the point of reference was the output of the middle cerebellar peduncles from the pons ) . both areas were then added , and final average data sets were used in further analysis . in cases of reduced volume of the hippocampal formation , the adjacent fluid spaces ( eg , the temporal horn of the lateral ventricle and the lateral part of the transverse fissure ) were also included into the voi .
necessary corrections of voi location were applied to particular frontal cross - sections , as well as to the axial plane , and care was taken not to cover the osseous structures of the temporal bone pyramids . for every localization , the size of voi was 8 cm . additionally , each subject had frontal measurement taken .
h mrs examination was carried out with a single - voxel method using press sequence .
routine 3-impulse sequences of 90 , 180 , 180 degrees and double crusher impulse were used .
the examination was performed with an automated standardization of the field in the entire encephalon / brain ( total shimming ) and in the examined sample ( local shimming ) . for water suppression ,
spectra were recorded within the following parameters : te=35 ms , tr=1500 ms , thickness = 15 mm , signal averages = 192 .
assignment of resonance lines of particular metabolites was based on n - acetylaspartate signal with chemical shift set to 2.0 ppm .
the spectra were analyzed using the manufacturer - supplied software package for the mrs ( marconi ) . in some cases ,
it was necessary to correct the phase manually in order to obtain a maximum of symmetrical signal of residual water and to maintain a proper baseline . relative concentration ratios of particular metabolites 
n - acetylaspartate ( naa ) , choline ( cho ) , myoinositol ( mi ) , glutamine and glutamate ( glx )  were analyzed in reference to the signal of unsuppressed water signal , and also to the signal of creatine , considering its level as an inner standard .
results analysis of clinical and biochemical data  age , mini - mental score ( mm - score ) , folic acid , vitamin b12 and homocysteine level  was performed including initial data of all subjects enrolled into the study .
evaluation of relative concentration ratios of metabolites from all vois , localized within frontal , medial and external temporal lobes , symmetrical on both sides , were performed in each case .
a comparison of some metabolic ratios of mrs in patients with mci , who on follow - up has stable disease ( sd ) , disease progression ( dp ) and conversion to ad , was performed .
the statistical analysis was carried out using the statistica for windows 7.0 ( statsoft , ok , usa ) software package .
the examination was performed on a group of 31 randomly selected subjects ( 19 females and 12 males ) with mci diagnosed under the care of the department of neurodegenerative disorders , medical research centre , polish academy of science .
all subjects underwent neurological and psychiatric tests , routine laboratory investigations and standard neuropsychological examinations .
patients with serious cns injuries , alcoholic abuse , diabetes , and serious hepatic and renal dysfunctions were excluded .
mci diagnosis was established by a team of specialists after analyzing all available information and test results .
mri and h mrs examination was performed on a 1.5 t eclipse ( marconi medical systems , usa ) scanner .
morphological mri examination of the brain was carried out in transverse planes , parallel to the longitudinal axis of the temporal lobe in se , fse and flair sequences , in t1- and t2-weighted images , and in the frontal plane perpendicular to the longitudinal axis of the temporal lobe in flair sequence .
we investigated the extent of cerebral atrophy , especially in medial and external temporal lobes and in frontal structures , as well as the presence of cortical - subcortical hyperintensive focuses ( which equal angiogenic lesions ) in t2-weighted images and flair sequence .
morphological examination enabled us to exclude other pathologies such as extensive ischemic lesions , tumors , paracerebral hematomas , and hydrocephalus , which might lead to cognitive disorders .
changes like leukoaraiosis and/or small single angiogenic focuses of gliosis were not exclusion criteria for the study .
the voi ( volume of interest ) was located in the frontal , medial and external temporal lobe regions , separately on each side . in case of medial temporal lobe covering the hippocampal formation ,
it was divided into 2 areas  the anterior ( the topographical point of reference in the coronal plane / layer was the level of dens ) and the posterior ( the point of reference was the output of the middle cerebellar peduncles from the pons ) . both areas were then added , and final average data sets were used in further analysis . in cases of reduced volume of the hippocampal formation , the adjacent fluid spaces ( eg , the temporal horn of the lateral ventricle and the lateral part of the transverse fissure ) were also included into the voi .
necessary corrections of voi location were applied to particular frontal cross - sections , as well as to the axial plane , and care was taken not to cover the osseous structures of the temporal bone pyramids . for every localization , the size of voi was 8 cm .
h mrs examination was carried out with a single - voxel method using press sequence .
routine 3-impulse sequences of 90 , 180 , 180 degrees and double crusher impulse were used .
the examination was performed with an automated standardization of the field in the entire encephalon / brain ( total shimming ) and in the examined sample ( local shimming ) . for water suppression ,
spectra were recorded within the following parameters : te=35 ms , tr=1500 ms , thickness = 15 mm , signal averages = 192 .
assignment of resonance lines of particular metabolites was based on n - acetylaspartate signal with chemical shift set to 2.0 ppm .
the spectra were analyzed using the manufacturer - supplied software package for the mrs ( marconi ) . in some cases ,
it was necessary to correct the phase manually in order to obtain a maximum of symmetrical signal of residual water and to maintain a proper baseline . relative concentration ratios of particular metabolites 
n - acetylaspartate ( naa ) , choline ( cho ) , myoinositol ( mi ) , glutamine and glutamate ( glx )  were analyzed in reference to the signal of unsuppressed water signal , and also to the signal of creatine , considering its level as an inner standard .
results analysis of clinical and biochemical data  age , mini - mental score ( mm - score ) , folic acid , vitamin b12 and homocysteine level  was performed including initial data of all subjects enrolled into the study .
evaluation of relative concentration ratios of metabolites from all vois , localized within frontal , medial and external temporal lobes , symmetrical on both sides , were performed in each case .
a comparison of some metabolic ratios of mrs in patients with mci , who on follow - up has stable disease ( sd ) , disease progression ( dp ) and conversion to ad , was performed .
the statistical analysis was carried out using the statistica for windows 7.0 ( statsoft , ok , usa ) software package .
all patients had annual clinical follow - up at least twice . at the beginning of the study , subjects were divided into 2 groups  9 subjects who had amnestic mci , and the others who had multidomain mci .
there were no statistical differences between groups of patients with multidomain mci and amnestic mci , including age , m - m score , level of vitamin b12 , folic acid and homocysteine ( p>0.05 ) .
comparison of mean value in some selected parameters including both groups is presented in table 1 . during clinical follow - up
( median 3 years ) 8 subjects had stable disease ( sd ) , 13 had progression of disease ( dp ) and 10 developed ad .
there was no significant difference between age , m - m score , vitamin b12 , folic acid and homocysteine level among these 3 groups of subjects ( p>0.05 ) .
statistical analyses of baseline metabolic ratios measurement using h mrs between the final 3 groups of patients , ( sd , dp and ad ) found significant difference in frontal lobes in mi / h20 ratio on left , between patients with stable disease ( 0.27 ) and those with progression ( 0.22 ) ( p=0.03 ) ( figure 1 ) . in the groups of patients with dp and those with conversion to ad
, there was a significant difference on the left side in ratio naa / cr ( 1.77 vs. 1.43 ) , ( p=0.02 ) ( figure 2 ) .
significant difference within temporal external lobes were found between patients with sd and dp in naa / h2o ratio on the left side ( 0.55 vs. 0.51 ) , ( p=0.04 ) ( figure 3 ) .
additionally , there were significant differences between patients with sd and ad in chol / cr ratio ( 0.99 vs. 0.88 ) on the right side ( p=0.04 ) and in mi / cr ( 1.09 vs. 0.62 ) on the left side ( p=0.03 ) .
a significant difference within the medial temporal lobe was found between patients with dp and ad in glx / h2o ratio ( 0.44 vs. 0.34 ) on the right side ( m - w u - test , p=0.02 ) . there were no other significant differences within h mrs metabolic ratios .
an example of h mrs study in patient with initial diagnosis of mci and clinical deterioration during 2 years of follow - up with final diagnosis of ad is presented in ( figure 4 ) ( a  initial h mrs , and after final diagnosis , control h mrs study 
b ) . summary of initial h mrs ratios of some metabolites in frontal , external and medial temporal lobes both sides are presented in table 3 .
proton magnetic resonance spectroscopy  h mrs  enables an in vivo noninvasive assessment of the degree of biochemical disorders in a specified voi of the examined tissue , as well as monitoring the progress of those changes in the course of the disease and its treatment [ 5,1725 ] .
the method we used , along with the parameters mentioned above , resulted in satisfactory quality of spectra in examined patients .
recent studies have demonstrated the value of h1mrs in many types of cognitive disorders , not only in degenerative diseases . in mrs diagnosis ,
normal tissues present a constant proton spectrum , while ratio changes of the metabolites can be considered as reflections of certain biochemical transformations .
several cytological and histochemical investigations have contributed to the study of the relationship between certain chemical substances and precisely defined intracellular structures or biochemical processes  physiological as well as pathological .
n - acetylaspartate is commonly considered as a neuronal marker due to its presence only in mature nerve cells .
there are several reports of age - dependent lowering of naa level in certain parts of the encephalon , which is being interpreted not only as an effect of a progressive decrease in number of neurons , but also as their dysfunction .
it also seems clear that there is a lowering of the naa concentration in atrophic structures of the limbic system in patients with ad , and a reverse correlation of the level of this metabolite with the level of dementia .
however , the h mrs examinations of the posterior part of the cingulate gyrus ( frontal lobe ) in patients with mci , carried out by the rochester group , did not prove statistically significant differences of the naa ratios as compared to the control group .
in our study , we found a significant difference between the ratio of naa / cr between patients with ds vs. dp in the left frontal lobe .
we also found significant difference in naa / h2o between patients with ds and dp in the left external temporal lobe .
we could not find any significant difference between naa / cr and naa / h2o within the medial temporal lobe on any sides .
this could due to the frequent technical difficulties mentioned before , as measurement of the medial temporal lobe ( hippocampus area ) is often inconvenient .
the neuronal integrity marker naa / cr or naa / h2o ratio ( independent of creatine level ) is currently declined in patients with progressive mci and those with conversion to ad compared to cognitively normal elderly subjects .
our findings generally agree with others reports that found lower levels of naa in patients with mci and deterioration of brain function and who convert to ad .
others reports indicated the left side more often has a drop in naa - rich neurons compare to the right side [ 2026 ] .
medial temporal lobes ( hippocampus structures ) are widely considered as the region in which the earliest ad pathologies occur .
therefore it seems that the lowering of naa concentration in this localization in patients with mci proves the theory of  successive  metabolic disorders in progression of dementia , according to which a lower concentration of myoinositol precedes the decline in naa concentration [ 2124 ] . in many reports , naa depletion seems to be good marker , as in metastasio et al .
single reports indicated that the significant reduction of naa has great predictive value within the occipital area in those based on roc with threshold level < 1.61 of naa / cr ratio ; other regions and others ratios were not significant in this study . despite this inhomogeneous data
, numerous studies have shown that naa plays an important role in neuronal integrity , with the left side more often affected in patients with progressive mci and in those with conversion to ad [ 1826 ] .
some studies have found an elevated level of mi / cr , with good correlation of disease progression and increase of neurofibrillary tangles in patients with conversion into ad . in our study
we did not find any of these findings ; on the contrary , we detected some depletion of mi / cr in patients with conversion to ad compared to those with stable disease , with a significant difference on the left external temporal lobe ( 1.09 vs. 0.62 ) .
we found the same tendency in mi / h2o ratio on the left frontal lobe between patients with disease stability and disease progression .
others reported differences between patients with mci and ad , with significantly higher signal ratio of mi / cr in ad .
others publications did not report any difference in this metabolite ratio in the group of patients with mci .
the differences in results of various groups of researchers could be explained by selection of the study population .
the same research group indicated different results , dependent on study group  for instance , no difference was found in selected population of patients with amnestic mci   compare to a heterogenous population with significant difference in mi signal .
some reports indicated that an elevated level of this metabolite in structures of the limbic system in patients with mci or dementia is connected with regional gliosis .
this theory is supported by the presence of visibly higher mi concentrations in glia cells than in neurocytes . however , thus far the exact role of mi in mci and ad is unclear .
there are many other disorders of the brain with mi disturbance , so specificity of this marker and ratio of mi / cr or mi / h2o seems to be low .
recent data suggests good discrimination using mi / cr ratio in different types of dementia using roc curve .
additional theory posits an extensive cellular capture of mi in patients at risk of dementia as the result of na / mi osmoregulator dysfunction .
the study of adults with down syndrome , who constitute a clinically exceptional group of subjects with 100% risk of dementia similar to the alzheimer s disease , demonstrated a greater that 50% rise of the myoinositol level with age compared to the healthy control group .
the authors associated this with an elevated activity of sodium - myoinositol transporter/ transmitter , which results from the existence of the additional 21 chromosome in down syndrome adults , which includes the gene - encoding protein of the transmitter . in our study , significant differences in mi / cr and mi / h2o were found in frontal and external temporal lobes , but not in the medial temporal lobe .
our h mrs study shows a significant difference between chol / cr ratio only in the external temporal lobe on the left side , with a significant drop in the chol / cr ratio between patients with stable disease and ad .
this result agrees with metastasio et al . , who showed a decreased , but not significant , depletion of chol / cr in mci patients with disease progression compare to those with stable disease in both hemispheres .
this could be related to cholinergic neuronal damage , which is indirectly confirmed by increased activity of choline acetyltransferase ( chat ) , and which probably represents a compensatory ( but insufficient ) response in ad .
impairment of mitochondrial activity seen in elderly patients , and more obviously in patients with ad , could be related to increase of mitochondrial membrane damage and evaluated level of membrane phospholipid   and decrease in phosphatidyl - choline and phosphatidylethanolamine described previously . in our study , significant difference in glutamine and glutamate ( glx ) ratio was noted only on the medial temporal lobe on the right side , which indicates disturbance of glx .
this finding agrees with data presented by kantarci et al . , who found a trend toward decreased glu + gln / cr ratios from normal to mci to ad , but there were no statistically significant differences .
detailed analysis of glutamine and glutamate in mci and ad could be explored using the new 3 t system , which currently is commercially available . in the medial temporal lobe h mrs
has several limitations that could influence our results and our interpretation . in view of the complicated spatial shape of the medial temporal - hippocampal formation ( which is considered to be the region first changed by the progression of dementia pathology ) and its relatively small size , our volume of interest also covered other tissue structures outside the target structure , which could have caused partial falsification of the results as to its volume effect   on the other hand , these structures belong to the limbic system , and show pathological changes in the subsequent stages of the disease .
according to reports in the literature , including the adjacent fluid spaces ( temporal horn of the lateral ventricle , lateral part of the transverse fissure ) into the voi should not affect the results .
some researchers claim that chemical shift imaging ( csi ) , also known as single voxel spectroscopy ( svs ) , which allows recording spectra from many neighboring voxels within the examined area , is better for assessment of metabolic disorders within the hippocampus because it enables a more precise measurement .
this theory was not corroborated in comparative studies of both of the methods used on a group of patients with temporal lobe epilepsy .
n - acetylaspartate is commonly considered as a neuronal marker due to its presence only in mature nerve cells .
there are several reports of age - dependent lowering of naa level in certain parts of the encephalon , which is being interpreted not only as an effect of a progressive decrease in number of neurons , but also as their dysfunction .
it also seems clear that there is a lowering of the naa concentration in atrophic structures of the limbic system in patients with ad , and a reverse correlation of the level of this metabolite with the level of dementia .
however , the h mrs examinations of the posterior part of the cingulate gyrus ( frontal lobe ) in patients with mci , carried out by the rochester group , did not prove statistically significant differences of the naa ratios as compared to the control group . in our study
, we found a significant difference between the ratio of naa / cr between patients with ds vs. dp in the left frontal lobe .
we also found significant difference in naa / h2o between patients with ds and dp in the left external temporal lobe .
we could not find any significant difference between naa / cr and naa / h2o within the medial temporal lobe on any sides .
this could due to the frequent technical difficulties mentioned before , as measurement of the medial temporal lobe ( hippocampus area ) is often inconvenient .
the neuronal integrity marker naa / cr or naa / h2o ratio ( independent of creatine level ) is currently declined in patients with progressive mci and those with conversion to ad compared to cognitively normal elderly subjects .
our findings generally agree with others reports that found lower levels of naa in patients with mci and deterioration of brain function and who convert to ad .
others reports indicated the left side more often has a drop in naa - rich neurons compare to the right side [ 2026 ] .
medial temporal lobes ( hippocampus structures ) are widely considered as the region in which the earliest ad pathologies occur .
therefore it seems that the lowering of naa concentration in this localization in patients with mci proves the theory of  successive  metabolic disorders in progression of dementia , according to which a lower concentration of myoinositol precedes the decline in naa concentration [ 2124 ] . in many reports , naa depletion seems to be good marker , as in metastasio et al .
single reports indicated that the significant reduction of naa has great predictive value within the occipital area in those based on roc with threshold level < 1.61 of naa / cr ratio ; other regions and others ratios were not significant in this study . despite this inhomogeneous data
, numerous studies have shown that naa plays an important role in neuronal integrity , with the left side more often affected in patients with progressive mci and in those with conversion to ad [ 1826 ] .
some studies have found an elevated level of mi / cr , with good correlation of disease progression and increase of neurofibrillary tangles in patients with conversion into ad . in our study
we did not find any of these findings ; on the contrary , we detected some depletion of mi / cr in patients with conversion to ad compared to those with stable disease , with a significant difference on the left external temporal lobe ( 1.09 vs. 0.62 ) .
we found the same tendency in mi / h2o ratio on the left frontal lobe between patients with disease stability and disease progression .
others reported differences between patients with mci and ad , with significantly higher signal ratio of mi / cr in ad .
others publications did not report any difference in this metabolite ratio in the group of patients with mci .
the differences in results of various groups of researchers could be explained by selection of the study population .
the same research group indicated different results , dependent on study group  for instance , no difference was found in selected population of patients with amnestic mci   compare to a heterogenous population with significant difference in mi signal .
some reports indicated that an elevated level of this metabolite in structures of the limbic system in patients with mci or dementia is connected with regional gliosis .
this theory is supported by the presence of visibly higher mi concentrations in glia cells than in neurocytes . however , thus far the exact role of mi in mci and ad is unclear .
there are many other disorders of the brain with mi disturbance , so specificity of this marker and ratio of mi / cr or mi / h2o seems to be low .
recent data suggests good discrimination using mi / cr ratio in different types of dementia using roc curve .
additional theory posits an extensive cellular capture of mi in patients at risk of dementia as the result of na / mi osmoregulator dysfunction .
the study of adults with down syndrome , who constitute a clinically exceptional group of subjects with 100% risk of dementia similar to the alzheimer s disease , demonstrated a greater that 50% rise of the myoinositol level with age compared to the healthy control group .
the authors associated this with an elevated activity of sodium - myoinositol transporter/ transmitter , which results from the existence of the additional 21 chromosome in down syndrome adults , which includes the gene - encoding protein of the transmitter . in our study , significant differences in mi / cr and mi / h2o were found in frontal and external temporal lobes , but not in the medial temporal lobe .
our h mrs study shows a significant difference between chol / cr ratio only in the external temporal lobe on the left side , with a significant drop in the chol / cr ratio between patients with stable disease and ad .
this result agrees with metastasio et al . , who showed a decreased , but not significant , depletion of chol / cr in mci patients with disease progression compare to those with stable disease in both hemispheres .
this could be related to cholinergic neuronal damage , which is indirectly confirmed by increased activity of choline acetyltransferase ( chat ) , and which probably represents a compensatory ( but insufficient ) response in ad .
impairment of mitochondrial activity seen in elderly patients , and more obviously in patients with ad , could be related to increase of mitochondrial membrane damage and evaluated level of membrane phospholipid   and decrease in phosphatidyl - choline and phosphatidylethanolamine described previously .
in our study , significant difference in glutamine and glutamate ( glx ) ratio was noted only on the medial temporal lobe on the right side , which indicates disturbance of glx .
this finding agrees with data presented by kantarci et al . , who found a trend toward decreased glu + gln / cr ratios from normal to mci to ad , but there were no statistically significant differences .
detailed analysis of glutamine and glutamate in mci and ad could be explored using the new 3 t system , which currently is commercially available . in the medial temporal lobe h mrs
has several limitations that could influence our results and our interpretation . in view of the complicated spatial shape of the medial temporal - hippocampal formation ( which is considered to be the region first changed by the progression of dementia pathology ) and its relatively small size , our volume of interest also covered other tissue structures outside the target structure , which could have caused partial falsification of the results as to its volume effect   on the other hand , these structures belong to the limbic system , and show pathological changes in the subsequent stages of the disease .
according to reports in the literature , including the adjacent fluid spaces ( temporal horn of the lateral ventricle , lateral part of the transverse fissure ) into the voi should not affect the results .
some researchers claim that chemical shift imaging ( csi ) , also known as single voxel spectroscopy ( svs ) , which allows recording spectra from many neighboring voxels within the examined area , is better for assessment of metabolic disorders within the hippocampus because it enables a more precise measurement .
this theory was not corroborated in comparative studies of both of the methods used on a group of patients with temporal lobe epilepsy .
h mrs seems to be a very sensitive method that provides biochemical information using an in vivo approach in patients with initial mci , who in significant numbers developed disease progression and/or converted to ad .
a potential advantage could be achieved by using 3 t systems , which can better discriminate quantization of glu + gln / cr and gln / cr ratios .
 summarybackgroundpurpose of study was evaluation of regional metabolic disorders using 1h mrs in patients with mci , as a predictor of clinical conversion to dementia based on clinical follow-up.material/methodsthe study group consisted of 31 subjects with diagnosis of mci based on criteria the mayo clinic group . 
 1h mrs was performed with a single - voxel method using press sequence . 
 the volume of interest ( voi ) was located in the hippocampal formation and posterior part of the cingulated gyrus.resultspatients had annual clinical control at least twice . at the beginning , 9 had amnestic mci and the others had multidomain mci . during follow - up ( median 3 yrs ) 8 subjects had stable disease ( sd ) , 13 had disease progression ( dp ) and 10 develop alzheimer disease ( ad ) . 
 baseline metabolic ratios ( 1h mrs ) between 3 groups indicated significant difference ( p<0.05 ) in left frontal lobe in mi / h20 ratio , between patients with sd ( 0.27 ) and dp . in comparing the groups with dp and ad , a significant difference in naa / cr ( 1.77 vs. 1.43 ) was found . 
 a significant difference within left temporal external lobes was found between sd and dp in naa / h2o ratio ( 0.55 vs. 0.51 ) . 
 an additional significant difference within medial temporal lobe was found between dp and ad in glx / h2o ratio ( 0.44 vs. 0.34 ) on the right side.conclusions1h mrs seems to be sensitive method allows prediction of which patients are liable to progress from mci to ad . 
 combined with other biomarkers of disease staging , it is an important approach in the preclinical ad diagnosis , as well as the assessment of dementia progression . 
Background
Aim of the study
Material and Methods
Inclusion criteria for patients and demographic characteristics of examined groups
MR and 
Statistical analysis
Results
Discussion
Changes of average NAA/Cr and NAA/H
Changes of average mI/Cr and mI/H
Changes of average Chol/Cr and Chol/H
Changes of average Chol/Cr and Chol/H
Conclusions