@article {597, title = {The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.}, journal = {JAMA}, volume = {282}, year = {1999}, month = {1999 Jul 07}, pages = {40-6}, abstract = {

CONTEXT: Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD.

OBJECTIVES: To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline.

DESIGN: The Cardiovascular Health Study, a population-based, prospective cohort study.

SETTING AND POPULATION: A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively.

MAIN OUTCOME MEASURES: Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus.

RESULTS: Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele.

CONCLUSIONS: Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.

}, keywords = {Aged, Aging, Alleles, Apolipoproteins E, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Diabetes Mellitus, Genotype, Humans, Mental Status Schedule, Prospective Studies, Risk Factors}, issn = {0098-7484}, doi = {10.1001/jama.282.1.40}, author = {Haan, M N and Shemanski, L and Jagust, W J and Manolio, T A and Kuller, L} } @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 {851, title = {Neuropsychological characteristics of mild cognitive impairment subgroups.}, journal = {J Neurol Neurosurg Psychiatry}, volume = {77}, year = {2006}, month = {2006 Feb}, pages = {159-65}, abstract = {

OBJECTIVE: To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study.

METHODS: MCI was classified as MCI-amnestic type (MCI-AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition.

RESULTS: MCI-AT (n = 10) had worse verbal and non-verbal memory performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI-MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI-MCDT cases, 22 (78.5\%) had memory deficits, and 6 (21.5\%) did not. MCI-MCDT with memory disorders had more language deficits than MCI-MCDT without memory disorders. By contrast, MCI-MCDT without memory deficits had more fine motor control deficits than MCI-MCDT with memory deficits.

CONCLUSIONS: The most frequent form of MCI was the MCI-MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16\% of all MCI cases and 21.5\% of the MCI-MCDT cases did not have memory impairment. Study of idiopathic amnestic and non-amnestic forms of MCI is essential for an understanding of the aetiology of MCI.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Amnesia, Cognition Disorders, Female, Humans, Male, Neuropsychological Tests, Psychometrics, Reference Values}, issn = {0022-3050}, doi = {10.1136/jnnp.2004.045567}, author = {Lopez, O L and Becker, J T and Jagust, W J and Fitzpatrick, A and Carlson, M C and DeKosky, S T and Breitner, J and Lyketsos, C G and Jones, B and Kawas, C and Kuller, L H} }