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People with Down syndrome (DS) develop Alzheimer's disease (AD) at higher rates and a younger age of onset compared to the general population. As the average lifespan of people with DS is increasing, AD is becoming an important health concern in this group. Neuroimaging is becoming an increasingly useful tool in understanding the pathogenesis of dementia development in relation to clinical symptoms. Furthermore, neuroimaging has the potential to play a role in AD diagnosis and monitoring of therapeutics. This review describes major recent findings from in vivo neuroimaging studies analysing DS and AD via ligand-based positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG)-PET, structural magnetic resonance imaging (sMRI), and diffusion tensor imaging (DTI). Electroencephalography (EEG) and retinal imaging are also discussed as emerging modalities. The review is organized by neuroimaging method and assesses the relationship between cognitive decline and neuroimaging changes. We find that amyloid accumulation seen on PET occurs prior to dementia onset, possibly as a precursor to the atrophy and white matter changes seen in MRI studies. Future PET studies relating tau distribution to clinical symptoms will provide further insight into the role this protein plays in dementia development. Brain activity changes demonstrated by EEG and metabolic changes seen via FDG-PET may also follow predictable patterns that can help track dementia progression. Finally, newer approaches such as retinal imaging will hopefully overcome some of the limitations of neuroimaging and allow for detection of dementia at an earlier stage.

The presence of age‐related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well‐established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry.ObjectiveTo characterize the initial informant reported age‐related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function.MethodsNon‐amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX‐DS informant interview were analyzed in a cross‐sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age‐related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age.ResultsAmnestic and non‐amnestic symptoms were present before evidence of informant‐reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001).ConclusionPremorbid amnestic and non‐amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options.

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Our results suggest that reduced expression of DNA repair genes on chromosome arms 1p and 19q may account for the increased chemosensitivity of LGGs with 1p19q codeletion.

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We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

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