***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To better estimate how frequently patients with low serum cobalamin ( Cbl ) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency , we prospect ively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period . Baseline hematologic , neuropsychiatric , and biochemical measurements were obtained , followed by a course of parenteral Cbl therapy and re assessment . A response to Cbl therapy was defined as one or more of the following : ( 1 ) an increase in hematocrit of 0.05 or more ; ( 2 ) a decrease in mean cell volume of 5 fL or more ; ( 3 ) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear ; and ( 4 ) an unequivocal and prompt improvement of neuropsychiatric abnormalities . Of the 300 patients with serum Cbl levels less than 200 pg/mL , 86 had one or more responses to Cbl therapy and 59 had no response . In 155 , insufficient data was available . In the Cbl-responsive patients , normal values were found for the following tests : hematocrit , 44 % ; mean cell volume less than or equal to 100 fL , 36 % ; white blood cell count , 84 % ; platelet count , 79 % ; serum lactic dehydrogenase , 43 % ; and serum bilirubin , 83 % . Peripheral blood smears were nondiagnostic in 6 % when review ed by the investigators , but 33 % as reported by routine laboratories . Serum Cbl levels in the 100 to 199 pg/mL range were present in 38 % . Neuropsychiatric abnormalities were noted in 28 % , often in the absence of anemia , macrocytosis , or both . Serum levels of methylmalonic acid and /or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94 % of the Cbl-responsive patients . We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency , even if anemia , an elevated mean cell volume , a marked depression of the serum Cbl , or other classic hematologic or biochemical abnormalities are lacking . Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency BACKGROUND A self-rating inventory has been developed to measure DSM-IV and ICD-10 diagnoses of major ( moderate to severe ) depression by the patients ' self-reported symptoms . This Major Depression Inventory ( MDI ) can be scored both according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology and according to severity scales by the simple total sum of the items . METHODS The Schedule for Clinical Assessment in Neuropsychiatry ( SCAN ) was used as index of validity for the clinician 's DSM-IV and ICD-10 diagnosis of major ( moderate to severe ) depression . The sensitivity and specificity of MDI was assessed in a sample of 43 subjects covering a spectrum of depressive symptoms . RESULTS The sensitivity of the MDI algorithms for major depression varied between 0.86 and 0.92 . The specificity varied between 0.82 and 0.86 . When using the total score of MDI the optimal cut-off score was estimated 26 and the total score was shown to be a sufficient statistic . LIMITATIONS The sample of subjects was limited . Patients with psychotic depression were not included . CONCLUSION The MDI was found to have a sensitivity and specificity which is acceptable . The question naire is brief and can be scored diagnostically by the DSM-IV and ICD-10 algorithms as well as by its simple total score OBJECTIVE To measure the prevalence of cobalamin ( vitamin B12 ) deficiency in geriatric out patients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment . DESIGN Prospect i ve study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays . In patients with serum cobalamin levels < or = 300 pg/mL , the response to cobalamin treatment in the group with levels of methylmalonic acid and /or homocysteine > 3 st and ard deviations ( SD ) above the mean for normals was compared with that of those without such elevations . SETTING Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center , Denver , CO . PATIENTS One-hundred and fifty-two consecutive out patients , ages 65 to 99 , were screened . Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospect ively evaluated and treated with cobalamin . MAIN OUTCOME MEASURES Cobalamin , methylmalonic acid , homocysteine , complete blood counts , neurologic examination , and neuropsychological testing . RESULTS The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and /or homocysteine elevated to > 3 SD was 14.5 % of the screened out patients . A similar proportion of patients with low normal serum cobalamin levels ( between 201 and 300 pg/mL ) demonstrated elevated metabolites > 3 SD ( 56 % ) compared with patients with low serum cobalamin levels ( < or = 200 pg/mL ) ( 62 % ) . Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospect ively . Results for complete blood count , lactate dehydrogenase , bilirubin , baseline neurologic score , and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites . The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment . One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment . CONCLUSION There was a high ( 14.5 % ) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly out patients . The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201 - 300 pg/mL compared with patients with low cobalamin levels ( < or = 200 pg/mL ) had markedly elevated metabolites which fell with cobalamin treatment . Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects A clinical trial of the effect of vitamin B12 therapy was conducted in 39 elderly subjects who had been found , in a community screening survey , to have low levels of serum B12 without a macrocytic anaemia or neuropathy . The study produced no evidence which suggests that in such subjects B12 is superior to placebo in effecting an improvement in psychiatric state or general well-being . There was a clear tendency for all the subjects to show an improvement during the trial , but this probably represents the therapeutic effect of involvement in a research exercise of this kind BACKGROUND Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported . METHODS A r and omized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid ( 0.40 - 2.00 micromol/l ) not previously treated with vitamin B-12 .  Cognitive function was assessed by the Cambridge Cognitive Examination  ( CAMCOG ) , Mini-Mental State Examination ( MMSE ) , and a 12-words learning test .  Symptoms of depression were evaluated by the Major Depression Inventory . The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later . RESULTS At baseline 78 ( 56 % ) individuals had cognitive impairment  judged from the CAMCOG score and 40 ( 29 % ) according to the MMSE ; 18 ( 13 % ) individuals had symptoms of depression . No improvement was found in cognitive function comparing the treatment and placebo group ( total CAMCOG score : P = 0.43 ) , nor among individuals with only slightly impaired cognitive function ( n = 44 , total CAMCOG score : P = 0.42 ) . The treatment group did not improve in depression score as compared to the placebo group ( P = 0.18 ) . LIMITATIONS The duration of impaired cognitive function was unknown . CONCLUSIONS A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function , and a rather high prevalence of depression was observed . However , vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period The gene for apolipoprotein E ( APOE ) is polymorphic , and its variant APOE4 is a major risk factor for the development of Alzheimer-type dementia ( AD ) . Another risk factor for AD appears to be negative cobalamin balance , which is very common in elderly people . Cobalamin and folate are interdependent and essential components of the one-carbon metabolism . Another important component is methylenetetrahydrofolate reductase ( MTHFR ) , the gene for which is also polymorphic . Thermolabile MTHFR ( tMTHFR ) , a gene variant that reduces the activity of its enzyme , is common in the general population . In the present study , 75 % of 140 AD patients had at least one APOE4 allele . The numbers of APOE4 and tMTHFR alleles correlated significantly with the serum folate levels , however , in opposite directions . The significance of this was augmented by an inverse correlation between APOE4 and tMTHFR . Thus , not only MTHFR but also APOE appears to be related to the one-carbon metabolism , suggesting that APOE4 and insufficient one-carbon metabolism may be synergistic risk factors for AD Abstract Dementia has a reversible cause in some cases , and these should be diagnosed without over-investigating the many patients with irreversible disease . We prospect ively studied the prevalence of reversible dementia in a memory clinic , determined the added value of investigations compared with clinical examination and assessed the outcome of treatment of potentially reversible causes by measuring ( 1 ) cognition , ( 2 ) disability in daily functioning , ( 3 ) behavioural changes and ( 4 ) caregiver burden .  Two hundred patients aged 65 years and over were examined , using the CAMDEX-N. If they were demented , the probable cause was diagnosed clinical ly and confirmed or excluded by a st and ard set of investigations , which were done in all patients . Of the patients , 170 ( mean age 79.2 years ) were demented ; 31 were treated for potentially reversible causes . At follow-up after 6 months , no patients showed complete reversal of dementia . Five patients improved on clinical impression , but only one on clinicial measurement . Thirty patients were cognitively impaired , but not demented ; seven were treated . Judged clinical ly , three patients improved , but on assessment only one did so ; she recovered completely . Blood tests often produced diagnostic results that were not expected clinical ly , but electroencephalography and computed tomography of the brain did not . None of the investigations had an effect on outcome of dementia after treatment . We conclude that in elderly patients referred to a memory clinic , the prevalence of reversible dementia is of the order of 1 % , if outcome after treatment is assessed by a st and ardized measurement . We recommend blood tests in all patients , to detect not only metabolic causes of dementia but also co-morbidity possibly worsening the dementia . Other investigations can be performed on clinical indication . Clinical evaluation remains the mainstay of diagnosis in dementia Routine determination of serum vitamin B12 levels is generally recommended as part of the screening of demented patients , based on the notion that vitamin B12 deficiency is one of the causes of reversible dementia . We studied the effects of vitamin B12 replacement therapy in a prospect i ve longitudinal study at a memory clinic , with special emphasis on assessment of severity of dementia : not only cognitive deterioration , but also disability in the activities of daily life , behavioural problems , and the burden experienced by the caregiver were examined using instruments of proven validity . In a series of 170 consecutive patients with dementia , subnormal serum vitamin B12 levels were found in 26 cases ( 15 % ) ; all but one fulfilled diagnostic criteria for possible Alzheimer 's disease .  Cobalamin supplementation was given to all patients and the effect was evaluated after 6 months . When the size and pattern of individual change scores , and the mean change scores on all instruments were taken into account , functioning after replacement therapy was not improved . When change scores of treated patients were compared with those of patients with Alzheimer 's disease ( n = 69 ) , vitamin B12 replacement did not result in slowing of the progression of dementia . Contrary to widely accepted beliefs , subnormal serum vitamin B12 levels are not a ( quantitatively ) important cause of 
    Output:
    
MAIN RESULTS From the two included studies ( Seal 2002 ; Fourniere 1997 ) of people with dementia and low serum vitamin B12 levels , there was no statistically significant evidence of treatment effect ,  vitamin B12 supplementation compared with placebo , on cognitive function .