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INTRODUCTION: Patients with subjective memory complaints (SMC) may include subgroups with different neuropsychological profiles and risks of cognitive impairment. METHODS: Cluster analysis was performed on two datasets (n: 630 and 734) comprising demographic and neuropsychological data from SMC and healthy controls (HC). Survival analyses were conducted on clusters. Bayesian model averaging assessed the predictive utility of clusters and other biomarkers. RESULTS: Two clusters with higher and lower than average cognitive performance were detected in SMC and HC. Assignment to the lower performance cluster increased the risk of cognitive impairment in both datasets (hazard ratios: 1.78 and 2.96; Plog‐rank: 0.04 and <0.001) and was associated with lower hippocampal volumes and higher tau/amyloid beta 42 ratios in cerebrospinal fluid. The effect of SMC was small and confounded by mood. DISCUSSION: This study provides evidence of the presence of cognitive clusters that hold biological significance and predictive value for cognitive decline in SMC and HC. Highlights: Patients with subjective memory complaints include two cognitive clusters.Assignment to the lower performance cluster increases risk of cognitive impairment.This cluster shows a pattern of biomarkers consistent with incipient Alzheimer's disease pathology.The same cognitive cluster structure is found in healthy controls.The effect of memory complaints on risk of cognitive decline is small and confounded. [ABSTRACT FROM AUTHOR]

Background: Alzheimer disease (AD) is the most common cause of dementia worldwide. It is known that cerebral amyloid aggregation and neurodegeneration are first steps in the physiopathology of AD. In the prodromal phase, a clinical diagnosis of amnesic mild cognitive impairment (aMCI) can be stablished, but not all subjects with MCI have a prodromal AD. The objective of this study was to determinate the impact of amyloid and FDG PET on the progression from aMCI to AD dementia. Methods: From October 2013 to March 2021, we prospectively selected 145 patients with a diagnosis aMCI. We excluded subjects older than 85 and those with structural brain lesion on brain MRI. Participants went through an amyloid and an FDG‐PET scans and were classified as positive or negative for amyloid and neurodegeneration. Patients were followed to stablish progression to AD dementia, 118 patients were followed up more than 36 months. Statistical analyses were done with STATA with significance set at p<0.05. All analyses were adjusted by age, gender, and education. Results: Demographics are shown on table 1. Sensibility, specificity, negative predictive value, and positive predictive value during the 4 years are shown on table 2. 88 patients were A+ and 74 patients were A‐. We divided the patients in 4 groups: A+/FDG+ (n:54), A+/FDG‐ (n:34), A‐/FDG‐ (40), A‐/FDG+(4). The mean of conversion were 39.95 months, this time depends on the result of the biomarkers. A‐ patients converted less and latter with a mean of 75.07 (IC 56.54→81) month, than A+ patients, that converted earlier (chi2 = 20.37 Pr>chi2 = 0.0000). A+/FDG+ converted with a mean of 27.79 (20.40‐33.21) months while A+/FDG‐ converted earlier with a mean of 37.38 (20.73‐48.26) month. (chi2 = 4.16 Pr>chi2 = 0.0415). Conclusions: Amyloid and FDG PET can help us to stablish prognosis in aMCI patients. We have observed that a positive amyloid PET is associated with an increased risk of progression to AD dementia. Even more, aMCI patients with both, amyloid PET and FDG, positive PETs progressed more often and earlier to AD dementia than those who have a positive amyloid PET but a negative FDG‐PET. [ABSTRACT FROM AUTHOR]

Abstract: A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75±7.1years) scanned with brain MRI and genotyped as part of Alzheimer''s Disease Neuroimaging Initiative. We carried out a replication study in an independent, non-overlapping sample of 51 elderly Caucasian subjects with MCI (mean age: 76±5.5years), scanned with brain MRI and genotyped for MTHFR, as part of the Cardiovascular Health Study. At each voxel in the brain, we tested to see where regional volume differences were associated with carrying one or more MTHFR ‘T’ alleles. In ADNI subjects, carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2–8% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5–1.5% per T allele at 1year follow-up, after adjusting for age and sex. We replicated these brain volume deficits of up to 5–12% per MTHFR T allele in the independent cohort of CHS subjects. As expected, the associations weakened after controlling for homocysteine levels, which the risk gene affects. The MTHFR risk variant may thus promote brain atrophy by elevating homocysteine levels. This study aims to investigate the spatially detailed effects of this MTHFR polymorphism on brain structure in 3D, pointing to a causal pathway that may promote homocysteine-mediated brain atrophy in elderly people with MCI. [Copyright &y& Elsevier]