@article {837, title = {Classification of vascular dementia in the Cardiovascular Health Study Cognition Study.}, journal = {Neurology}, volume = {64}, year = {2005}, month = {2005 May 10}, pages = {1539-47}, abstract = {

OBJECTIVE: To describe the diagnostic classification of subjects with incident vascular dementia (VaD) participating in the Cardiovascular Health Study (CHS) Cognition Study.

METHODS: The CHS classified 480 incident cases between 1994 and 1999 among 3,608 CHS participants who had brain MRI in 1992 through 1994 and in 1997 through 1998. The patients were diagnosed before and after reviewing the brain MRI.

RESULTS: The pre-MRI classification showed that 52 participants had VaD and 76 had both Alzheimer disease (AD) and VaD. The post-MRI classification showed that the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria classified 61 subjects as having VaD, the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l{\textquoteright}Enseignement en Neurosciences (NINDS-AIREN) criteria classified 43 subjects as having probable VaD and 10 as possible VaD, and the State of California Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Center (ADDTC) criteria classified 117 as having probable VaD and 96 as possible. The combination of the ADDTC and National Institute of Neurological and Communication Disorders and Stroke-Alzheimer{\textquoteright}s Disease and Related Disorders Association criteria was used to examine the spectrum of vascular disease in dementia. The dementia was attributable to only vascular factors in 56 cases (probable VaD); VaD coexisted with AD in 61 cases, although the VaD component was the leading cause of dementia (probable VaD with AD); AD was the leading cause of dementia in 61 cases (possible VaD and probable AD); and in 29 cases, it was not clear that either AD or VaD was the primary diagnosis (possible AD and possible VaD).

CONCLUSIONS: None of the clinical criteria for VaD identified the same group of subjects. The diagnosis of vascular dementia is difficult in epidemiologic studies because poststroke dementia can be due to Alzheimer disease (AD) and evidence of vascular disease can be found in the MRI of dementia cases without clinical strokes. Whether the clinical progression is related to AD pathology or vascular disease is difficult to establish.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cerebral Arteries, Cohort Studies, Dementia, Vascular, Diagnosis, Differential, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Predictive Value of Tests, Stroke, United States}, issn = {1526-632X}, doi = {10.1212/01.WNL.0000159860.19413.C4}, author = {Lopez, O L and Kuller, L H and Becker, J T and Jagust, W J and DeKosky, S T and Fitzpatrick, A and Breitner, J and Lyketsos, C and Kawas, C and Carlson, M} } @article {838, title = {Determinants of vascular dementia in the Cardiovascular Health Cognition Study.}, journal = {Neurology}, volume = {64}, year = {2005}, month = {2005 May 10}, pages = {1548-52}, abstract = {

OBJECTIVE: The authors evaluated 3,375 participants without dementia at the time of MRI in 1991 to 1994 over 5.7 years for incident dementia and type of dementia.

METHODS: Incidence of and risk factors for vascular dementia (VaD) were measured using both pre-MRI and modified State of California Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Centers (ADDTC) post-MRI review and further classified Alzheimer disease (AD) by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer{\textquoteright}s Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

RESULTS: Approximately 44\% (213) of 480 incident dementia cases were classified as possible or probable VaD by ADDTC. The incidence of VaD increased with age and was greater in blacks than whites. Risk factors for VaD included age, Modified Mini-Mental State Examination, high white matter grade, number of MRI infarcts, ventricular size, and history of stroke.

CONCLUSIONS: Vascular disease in the brain is prevalent among incident dementia cases. There is a substantial overlap between cases classified as Alzheimer disease by Neurological and Communicative Disorders and Stroke and the Alzheimer{\textquoteright}s Disease and Related Disorders Association and vascular dementia (VaD) by modified State of California Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Centers criteria. The substantial contribution of vascular disease would be missed without inclusion of MRI. Treatment of risk factors for VaD could have an important impact on incidence of dementia.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain, Cardiovascular Diseases, Cerebral Arteries, Cerebral Infarction, Cohort Studies, Comorbidity, Continental Population Groups, Dementia, Vascular, Female, Humans, Lateral Ventricles, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Neuropsychological Tests, Risk Factors, Sex Factors}, issn = {1526-632X}, doi = {10.1212/01.WNL.0000160115.55756.DE}, author = {Kuller, L H and Lopez, O L and Jagust, W J and Becker, J T and DeKosky, S T and Lyketsos, C and Kawas, C and Breitner, J C S and Fitzpatrick, A and Dulberg, C} } @article {6816, title = {Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).}, journal = {Mol Psychiatry}, volume = {20}, year = {2015}, month = {2015 Feb}, pages = {183-92}, abstract = {

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 {\texttimes} 10(-9), MIR2113; rs17522122, P=2.55 {\texttimes} 10(-8), AKAP6; rs10119, P=5.67 {\texttimes} 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 {\texttimes} 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29\% (s.e.=5\%) and 28\% (s.e.=7\%), respectively. Using polygenic prediction analysis, ~1.2\% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 {\texttimes} 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer{\textquoteright}s disease: TOMM40, APOE, ABCG1 and MEF2C.

}, keywords = {Aged, Aged, 80 and over, Atherosclerosis, Cognition, Cognition Disorders, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, HMGN1 Protein, Humans, Male, Middle Aged, Neuropsychological Tests, Phenotype, Polymorphism, Single Nucleotide, Scotland}, issn = {1476-5578}, doi = {10.1038/mp.2014.188}, author = {Davies, G and Armstrong, N and Bis, J C and Bressler, J and Chouraki, V and Giddaluru, S and Hofer, E and Ibrahim-Verbaas, C A and Kirin, M and Lahti, J and van der Lee, S J and Le Hellard, S and Liu, T and Marioni, R E and Oldmeadow, C and Postmus, I and Smith, A V and Smith, J A and Thalamuthu, A and Thomson, R and Vitart, V and Wang, J and Yu, L and Zgaga, L and Zhao, W and Boxall, R and Harris, S E and Hill, W D and Liewald, D C and Luciano, M and Adams, H and Ames, D and Amin, N and Amouyel, P and Assareh, A A and Au, R and Becker, J T and Beiser, A and Berr, C and Bertram, L and Boerwinkle, E and Buckley, B M and Campbell, H and Corley, J and De Jager, P L and Dufouil, C and Eriksson, J G and Espeseth, T and Faul, J D and Ford, I and Gottesman, R F and Griswold, M E and Gudnason, V and Harris, T B and Heiss, G and Hofman, A and Holliday, E G and Huffman, J and Kardia, S L R and Kochan, N and Knopman, D S and Kwok, J B and Lambert, J-C and Lee, T and Li, G and Li, S-C and Loitfelder, M and Lopez, O L and Lundervold, A J and Lundqvist, A and Mather, K A and Mirza, S S and Nyberg, L and Oostra, B A and Palotie, A and Papenberg, G and Pattie, A and Petrovic, K and Polasek, O and Psaty, B M and Redmond, P and Reppermund, S and Rotter, J I and Schmidt, H and Schuur, M and Schofield, P W and Scott, R J and Steen, V M and Stott, D J and van Swieten, J C and Taylor, K D and Trollor, J and Trompet, S and Uitterlinden, A G and Weinstein, G and Widen, E and Windham, B G and Jukema, J W and Wright, A F and Wright, M J and Yang, Q and Amieva, H and Attia, J R and Bennett, D A and Brodaty, H and de Craen, A J M and Hayward, C and Ikram, M A and Lindenberger, U and Nilsson, L-G and Porteous, D J and R{\"a}ikk{\"o}nen, K and Reinvang, I and Rudan, I and Sachdev, P S and Schmidt, R and Schofield, P R and Srikanth, V and Starr, J M and Turner, S T and Weir, D R and Wilson, J F and van Duijn, C and Launer, L and Fitzpatrick, A L and Seshadri, S and Mosley, T H and Deary, I J} }