The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Bilingualism in older Mexican-American immigrants is associated with higher scores on cognitive screening

Abstract Background Bilingualism may protect against cognitive aging and delay the onset of dementia. However, studies comparing monolinguals and bilinguals on such metrics have produced inconsistent results complicated by confounding variables and methodological concerns. Methods We addressed this issue by comparing cognitive performance in a more culturally homogeneous cohort of older Spanish-speaking monolingual (n = 289) and Spanish-English bilingual (n = 339) Mexican-American immigrants from the Sacramento Longitudinal Study on Aging. Results After adjusting for demographic differences and depressive symptoms, both groups performed similarly at baseline on verbal memory but the bilingual group performed significantly better than the monolingual group on a cognitive screening test, the Modified Mini-Mental State Examination (3MS; p < 0.001). Group differences on the 3MS were driven by language/executive and language/praxis factors. Within the bilingual group, neither language of testing nor degree of bilingualism was significantly associated with 3MS or verbal memory scores. Amongst individuals who performed in the normal or better range on both tests at baseline and were followed for an average of 6 years, both monolinguals and bilinguals exhibited similar rates of cognitive decline on both measures. Conclusions These findings suggest that bilingualism is associated with modest benefits in cognitive screening performance in older individuals in cross-sectional analyses that persist across longitudinal analyses. The effects of bilingualism should be considered when cognitively screening is performed in aging immigrant populations

The Progressive Acalculia Presentation of Parietal Variant Alzheimer\u27s Disease.

BACKGROUND: Many patients with early-onset Alzheimer\u27s disease (EOAD; age of onset \u3c65 \u3eyears) have non-amnestic presentations involving language (logopenic primary progressive aphasia, lvPPA), visuospatial abilities (posterior cortical atrophy, PCA), and even asymmetric symptoms consistent with corticobasal syndrome (CBS). An inferior parietal lobule variant of EOAD commonly presents with progressive difficulty with calculations. METHODS: We reviewed 276 EOAD patients for presentations with predominant acalculia. These patients were diagnosed with clinically probable Alzheimer\u27s disease (AD) verified by positron emission tomography (PET) or cerebrospinal fluid amyloid-β or tau biomarkers. RESULTS: We identified 18 (9M/9F) (6.5%) EOAD patients with progressive acalculia that did not meet most criteria for lvPPA, visual PCA, or CBS. Their ages of onset and presentation were 56.6 (5.0) and 59.4 (6.5), respectively. Their acalculia was consistent with a primary acalculia ( anarithmetia ) not explained by language or visuospatial impairments. Many also had anomia (14/18), ideomotor apraxia (13/18), and the complete Gerstmann\u27s syndrome (7/18). Visual analysis of their diverse magnetic resonance imaging disclosed biparietal atrophy, disproportionately worse on the left. CONCLUSIONS: Primary acalculia may be the most common manifestation of an inferior parietal presentation of EOAD affecting the left intraparietal sulcus. This parietal variant also commonly involves progressive anomia, ideomotor apraxia, and other elements of Gerstmann\u27s syndrome. The early recognition of patients with this variant, which is distinguishable from lvPPA, visual PCA, or CBS, would be facilitated by its recognition as a unique subtype of EOAD

Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding

OBJECTIVE: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. METHODS: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [(11)C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. RESULTS: Low plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. CONCLUSIONS: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction

Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding.

ObjectiveWe investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association.MethodsOur dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [(11)C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes.ResultsLow plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A.ConclusionsOur data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction

Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding.

ObjectiveWe investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association.MethodsOur dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [(11)C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes.ResultsLow plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A.ConclusionsOur data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction