***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 
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    Input: Article abstract —We examined the pattern of neuroanatomic abnormalities in adults with Down 's syndrome ( DS ) and the cognitive correlates of these abnormalities . Specifically , we compared this pattern with what would be predicted by the hypotheses attributing DS pathology to either premature aging or Alzheimer 's disease . We measured a number of brain regions on MRIs of 25 subjects : 13 persons with the DS phenotype and 12 age- and sex-matched healthy volunteers . Study participants had no history of cardiovascular disease , diabetes , thyroid dysfunction , or seizure disorder . After statistical adjustment for differences in body size , we found that , in comparison with controls , DS subjects had substantially smaller cerebral and cerebellar hemispheres , ventral pons , mammillary bodies , and hip-pocampal formations . In the cerebellar vermis of DS subjects , we observed smaller lobules VI to VIII without appreciable differences in other regions . In addition , we noted trends for shrinkage of the dorsolateral prefrontal cortex , anterior cingulate gyrus , inferior temporal and parietal cortices , parietal white matter , and pericalcarine cortex in DS subjects compared with normal controls . The parahippocampal gyrus was larger in DS subjects . We found no significant group differences in the volumes of the prefiontal white matter , the orbitofiontal cortex , the pre- and post central gyri , or the basal ganglia . We conclude that the pattern of selective cerebral damage in DS does not clearly fit the predictions of the premature aging or Alzheimer 's disease hypotheses . To examine the relationship between brain abnormalities and cognitive deficits observed in DS , we correlated the size of brain regions that were significantly reduced in DS with performance on tests of intelligence and language . The correlational analysis suggested age-related decline in the DS subjects in general intelligence and basic linguistic skills . General intelligence and mastery of linguistic concepts correlated negatively with the volume of the parahippocampal gyrus . There was no relationship between total brain size and the cognitive variables BACKGROUND While neuropathological studies indicate a high risk for Alzheimer 's disease in adults with Down 's syndrome , neuropsychological studies suggest a lower prevalence of dementia . In this study , cognitive deterioration in adults with Down 's syndrome was examined prospect ively over 4 years to establish rates and profiles of cognitive deterioration . METHODS Fifty-seven people with Down 's syndrome aged 30 years or older were assessed using a battery of neuropsychological tests on five occasions across 50 months . Assessment s of domains of cognitive function known to change with the onset of Alzheimer related dementia were employed . These included  tests of learning , memory , orientation , agnosia , apraxia and aphasia .  The individual growth trajectory methodology was used to analyse change over time . RESULTS Severe cognitive deterioration , such as acquired , apraxia and agnosia , was evident in 28.3 % of those aged over 30 and a higher prevalence of these impairments was associated with older age . The rate of cognitive deterioration also increased with age and degree of pre-existing cognitive impairment . Additionally , deterioration in memory , learning and orientation preceded the acquisition of aphasia , agnosia and apraxia . CONCLUSIONS The prevalence of cognitive impairments consistent with the presence of Alzheimer 's disease is lower than that suggested by neuropathological studies . The pattern of the acquisition of cognitive impairments in adults with Down 's syndrome is similar to that seen in individuals with Alzheimer 's disease who do not have Down 's syndrome Frontotemporal dementia ( FTD ) is often misdiagnosed as Alzheimer ’s disease ( AD ) . We hypothesized that the first symptoms associated with FTD would be different from those seen in AD and that the first symptoms in FTD would reflect loss of function in the frontal region with the greatest degree of degeneration . The objective of the study was to compare the earliest symptoms in patients with FTD and AD , and to delineate the symptoms that were associated with right , left or bilateral frontotemporal degeneration in FTD . The first symptoms in 52 FTD and 101 AD patients were determined in retrospect . Based on functional imaging studies , the FTD patients were divided into those with predominantly bilateral ( n = 15 ) , left-sided ( n = 19 ) and right-sided ( n = 18 ) patterns of atrophy . The results showed that disinhibition , social awkwardness , passivity and loss of executive function were more common in FTD , while memory loss was more common in AD . Disinhibition was greatest in the asymmetric right-sided group , language dysfunction was commonest in the asymmetric left-sided group and loss of executive function was most frequent in the bilateral group . In summary , different first symptoms appeared in FTD and AD , which may help distinguish between the diseases . The anatomic site for FTD largely determined the kind of first symptoms BACKGROUND The clinical and neuropathological features associated with dementia in Down 's syndrome ( DS ) are not well established . Aims To examine clinico-pathological correlations and the incidence of cognitive decline in a cohort of adults with DS . METHOD A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000 . At outset , 87 participants were dementia-free , with a median age of 38 years . Assessment s included the  Prudhoe Cognitive Function Test ( PCFT )  and the  Adaptive Behavior Scale ( ABS )  , to measure cognitive and behavioural deterioration . Dementia was diagnosed from case records and caregivers ' reports . RESULTS Eighteen ( 21 % ) patients developed dementia during follow-up , with a median age of onset 55.5 years ( range 45 - 74 ) . The PCFT demonstrated cognitive decline among those with a less severe intellectual disability ( mild and moderate ) but not among the profoundly disabled people ( severe and profound ) . Clinical dementia was associated with neuropathological features of Alzheimer 's disease , and correlated with neocortical neurofibrillary tangle densities . At the age of 60 years and above , a little more than 50 % of patients still alive had clinical evidence of dementia . CONCLUSIONS Clinical dementia associated with measurable cognitive and functional decline is frequent in people with DS after middle age , and can be readily diagnosed among less severely intellectually disabled persons using measures of cognitive function such as the  PCFT  and behavioural scales such as the ABS . In the more profoundly disabled people , the diagnosis of dementia is facilitated by the use of behavioural and neurological criteria . In this study , the largest prospect i ve DS series including neuropathology on deceased patients , the density of neurofibrillary tangles related more closely to the dementia of DS than senile plaques . In people with DS surviving to middle and old age , the development of dementia of Alzheimer type is frequent but not inevitable , and some people with DS reach old age without clinical features of dementia CYP17 and CYP19 are involved in the peripheral synthesis of estrogens , and polymorphisms in CYP17 and CYP19 have been associated with increased risk of estrogen-related disorders . Women with Down syndrome ( DS ) have early onset and high risk for Alzheimer 's disease ( AD ) . We conducted a prospect i ve community-based cohort study to examine the relationship between SNPs in CYP17 and CYP19 and cumulative incidence of AD , hormone levels and sex hormone binding globulin in women with DS . Two hundred and thirty-five women with DS , 31 to 67 years of age and nondemented at initial examination , were assessed for cognitive and functional abilities , behavioral/psychiatric conditions , and health status at 14 - 20 month intervals over five assessment cycles . We genotyped these individuals for single-nucleotide polymorphisms ( SNPs ) in CYP17 and CYP19 . Four SNPs in CYP17 were associated with a two and one half-fold increased risk of AD , independent of APOE genotype . Four SNPs in CYP19 were associated with a two-fold increased risk of AD , although three were significant only in those without an APOE ε4 allele . Further , carrying high risk alleles in both CYP17 and CYP19 was associated with an almost four-fold increased risk of AD ( OR = 3.8 , 95 % CI , 1.6 - 9.5 ) and elevated sex hormone binding globulin in postmenopausal women . The main effect of the CYP17 and CYP19 variants was to decrease the age at onset . These findings suggest that genes contributing to estrogen bioavailability influence risk of AD in women with DS Research based on retrospective reports by carers suggests that the presentation of dementia in people with Down 's syndrome may differ from that typical of Alzheimer 's disease ( AD ) in the general population , with the earliest changes tending to be in personality or behaviour rather than in memory . This is the first long‐term prospect i ve study to test the hypothesis that such changes , which are more typical of dementia of frontal type ( DFT ) in the general population , mark the pre clinical stage of AD in DS BACKGROUND Recent research has suggested a specific impairment in frontal-lobe functioning in the pre clinical stages of Alzheimer 's disease ( AD ) in people with Down 's syndrome ( DS ) , characterised by prominent changes in personality or behaviour . The aim of the current paper is to explore whether particular kinds of change ( namely executive dysfunction ( EDF ) , disinhibition and apathy ) , associated in the literature with disruption of different underlying frontal-subcortical circuits , are a ) more or less frequently reported than others and b ) related to poor performance on tasks involving different cognitive processes . METHOD Seventy-eight participants ( mean age 47 years , range 36 - 72 ) with DS and mild to moderate intellectual disability ( based on ICD-10 criteria ) , without a diagnosis of dementia of Alzheimer 's type ( DAT ) or other psychiatric disorders , were selected from a larger sample of older adults with DS ( n = 122 ) . Dementia diagnosis was based on the CAMDEX informant interview , conducted with each participant 's main carer . Informant-reported changes in personality/behaviour and memory were recorded . Participants were scored based on symptoms falling into three behavioural domains and completed five executive function ( EF ) tasks , six memory tasks ( two of which also had a strong executive component ) and the BPVS ( as a measure of general intellectual ability ) . Multiple regression analyses were conducted to determine the degree to which the behavioural variables of ' EDF ' , ' disinhibition ' and ' apathy ' , along with informant-reported memory decline and antidepressant medication use , predicted performance on the cognitive tasks ( whilst controlling for the effects of age and general intellectual ability ) . RESULTS Strikingly , disinhibited behaviour was reported for 95.7 % of participants with one or more behavioural change ( n = 47 ) compared to 57.4 % with reported apathy and 36.2 % with reported EDF . ' Disinhibition ' score significantly predicted performance on three EF tasks ( design ed to measure planning , response inhibition and working memory ) and an object memory task , ( also thought to place high dem and s on working memory ) , while ' apathy ' score significantly predicted performance on two different tasks , those measuring spatial reversal and prospect i ve memory ( p < 0.05 ) . Informant reported memory decline was associated only with performance on a delayed recall task while antidepressant medication use was associated with better performance on a working memory task ( p < 0.05 ) . CONCLUSION Observed dissociation between performance on cognitive tasks associated with reported apathy and disinhibition is in keeping with proposed differences underlying neural circuitry and supports the involvement of multiple frontal-subcortical circuits in the early stages of DAT in DS . However , the prominence of disinhibition in the behavioural profile ( which more closely resembles that of disinhibited subtype of DFT than that of AD in the general population ) leads us to postulate that the serotonergically mediated orbitofrontal circuit may be disproportionately affected . A speculative theory is developed regarding the biological basis for observed changes and discussion is focused on how this underst and ing may aid us in the development of treatments directly targeting underlying abnormalities BACKGROUND Prevalence of Alzheimer 's disease in people with Down 's syndrome is very high , and many such individuals who are older than 40 years have pathological changes characteristic of Alzheimer 's disease . Evidence to support treatment with Alzheimer 's drugs is inadequate , although memantine is beneficial in transgenic mice . We aim ed to assess safety and efficacy of memantine on cognition and function in individuals with Down 's syndrome . METHODS In our prospect i ve r and omised double-blind trial , we enrolled adults ( > 40 years ) with karyotypic or clinical ly diagnosed Down 's syndrome , with and without dementia , at four learning disability centres in the UK and Norway . We r and omly allocated participants ( 1:1 ) to receive memantine or placebo for 52 weeks by use of a computer-generated sequence and a minimisation algorithm to ensure balanced allocation for five prognostic factors ( sex , dementia , age group , total Down 's syndrome attention , memory , and executive function scales [ DAMES ] score , and centre ) . The primary outcome was change in cognition and function , measured with DAMES scores and the adaptive behaviour scale ( ABS ) parts I and II . We analysed differences in DAMES and ABS scores between groups with analyses of covariance or quantile regression in all patients who completed the 52 week assessment and had available follow-up data . This study is registered , number IS RCT N47562898 . 
    Output:
    
We conducted a systematic review selecting studies employing  cognitive assessment s. Summary : We identified few studies using objective measurements to determine whether cognitive aspects associated with the frontal lobe correlate with dementia in this population .
We observed a tendency toward such correlations .