Validity of dementia and Alzheimer's disease diagnoses in Finnish national registers.

BACKGROUND: We investigated dementia and Alzheimer disease (AD) diagnoses in three national registers in Finland: the Hospital Discharge Register (HDR), the Drug Reimbursement Register, and the Causes of Death Register (CDR). METHODS: The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study was used as the gold standard. Participants were first evaluated in 1972 to 1987, and were reexamined in 1998 and in 2005 to 2008. RESULTS: Two approaches were used for the HDR: with a time restriction (considering "positive" only those cases recorded in the HDR before CAIDE study evaluations) and without a time restriction. Sensitivity of the HDR was 13.7% with time restriction and 51% without time restriction (dementia), and 15.6% with time restriction 55.6% without time restriction (AD). The positive predictive value (PPV) was 87.5% with time restriction and 96.3% without time restriction (dementia), and 100% for AD. Sensitivity and PPV of the HDR were greater after 1998. For AD in the Drug Reimbursement Register alone, sensitivity was 63.5% and PPV was 97.1%; together with the HDR, sensitivity became 65.4% with time restriction and 71.1% without time restriction, and PPV was 100%. For dementia in the CDR, sensitivity was 62.2% and PPV was 100%. CONCLUSIONS: Diagnoses in registers have very good accuracy, but underestimation of dementia/AD occurrence may cause an underestimation of associations with risk/protective factors.

Serum and lipoprotein sitostanol and non-cholesterol sterols after an acute dose of plant stanol ester on its long-term consumption.

PURPOSE: Chronic inhibition of cholesterol absorption with large doses of plant stanol esters (staest) alters profoundly cholesterol metabolism, but it is unknown how an acute inhibition with a large staest dose alters the postprandial serum and lipoprotein cholesterol precursor, plant sterol, and sitostanol contents. METHODS: Hypercholesterolemic subjects, randomly and double-blind divided into control (n = 18) and intervention groups (n = 20), consumed experimental diet without and with staest (plant stanols 8.8 g/day) for 10 weeks. Next morning after a fasting blood sample (0 h), the subjects had a breakfast without or with staest (4.5 g of plant stanols). Blood sampling was repeated 4 h later. Lipoproteins were separated with ultracentrifugation, and sterols were measured with gas-liquid chromatography. RESULTS: In 0-h chylomicrons and VLDL, plant sterols were lower in staest than in controls. Postprandially, cholestenol (cholesterol synthesis marker) was reduced in chylomicrons in staest compared with controls (-0.13 ± 0.04 µg/dL vs. 0.01 ± 0.08 µg/dL, P < 0.05). Staest decreased postprandially avenasterol in chylomicrons (P < 0.05 from 0 h). Sitostanol was high at 0 h by chronic staest in serum and VLDL but not in chylomicrons. Postprandial sitostanol was increased by staest in VLDL only. CONCLUSIONS: Chronic cholesterol absorption inhibition with large amount of plant stanol esters decreases plant sterols in triglyceride-rich lipoproteins. Acute plant stanol ester consumption increases sitostanol content in triglyceride-rich lipoproteins but suggests to decrease the risk of plant sterol and plant stanol accumulation into vascular wall by chylomicrons.

Multimodal Preventive Trial for Alzheimer's Disease: MIND-ADmini Pilot Trial Study Design and Progress.

BACKGROUND: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer's disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. OBJECTIVES: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. METHODS: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. RESULTS: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. CONCLUSIONS: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).

Plasma Abeta42 and Abeta40 as markers of cognitive change in follow-up: a prospective, longitudinal, population-based cohort study.

BACKGROUND: Single measurements of plasma Aß are not useful in the diagnostics of Alzheimer's disease (AD). However, changes in plasma Aß levels during repeated testing may be helpful in the prediction and evaluation of progression of the incipient AD or mild cognitive impairment. OBJECTIVE: To examine the relation of baseline and serial plasma Aß levels to cognitive change in follow-up. METHODS: 269 subjects (52 cognitively impaired and 217 controls) from a population-based cohort were clinically followed up from 3 to 6 years. Serial plasma samples were available from 70 subjects who were followed up for 3 years and 43 subjects followed for 6 years. The plasma Aß levels were measured using ELISA. RESULTS: Subjects who declined cognitively during the follow-up had lower levels of plasma Aß42 at the baseline. Plasma Aß42 and the Aß42/Aß40 ratio decreased (-2.4 pg/ml for Aß42 in 6 years) in those who declined in follow-up, whereas Aß42 and the Aß42/Aß40 ratio increased in the subjects who remained cognitively stable or improved in follow-up. Subjects using acetylsalicylic acid, dipyridamole, antidiabetic or anticoagulant drugs as well as subjects with coronary heart disease had higher levels of Aß40. CONCLUSIONS: Low or decreasing plasma Aß42 during the follow-up is associated with cognitive decline. Serial measurement of plasma Aß42 may be useful in the detection of the subjects who are at risk for cognitive decline.

Twenty-one year tracking of serum non-cholesterol sterols. The Cardiovascular Risk in Young Finns study.

BACKGROUND AND AIM: To show tracking of cholesterol metabolism, the ratios to cholesterol of e.g. serum cholestenol, desmosterol, and lathosterol, reflecting cholesterol synthesis, and cholestanol, campesterol, avenasterol and sitosterol, reflecting cholesterol absorption, were measured 21 years apart. METHODS AND RESULTS: In random population samples initially comprising 12- (n=162), 15- (n=158), and 18-year-old (n=148) males participating in the Cardiovascular Risk in Young Finns Study, serum sterols and squalene were measured with gas-liquid chromatography in 1980 and 2001. Quartiles of cholestanol, indicating low to high cholesterol absorption, were defined from the cholestanol values in 1980. Serum cholesterol increased in the oldest age group only, but synthesis markers (except desmosterol) increased in all age groups after the follow-up (e.g. lathosterol, total population +47.3+/-2.6% (SE), P<0.001). Campesterol (+69.0+/-3.0%, P<0.001) and sitosterol increased, avenasterol was unchanged, and cholestanol decreased (-6.2+/-0.7%, P<0.001), respectively. The 1980 synthesis and absorption markers were interrelated with respective values 21 years later in all age groups and quartiles (e.g. lathosterol, total population 1980 vs. 2001 r=0.460, cholestanol 1980 vs. 2001 r=0.593, P<0.001 for both). Synthesis markers were highest in the first and lowest in the fourth quartile both in 1980 and 2001 (e.g. 2001, desmosterol, quartile 1, 99+/-9, quartile 4, 83+/-2 microg/mg of cholesterol, P<0.05). CONCLUSIONS: Cholesterol metabolism is significantly tracked in adolescent males over the follow-up of 21 years. Thus, high cholesterol synthesis and low absorption characterize subjects with the lowest cholestanol quartile, while those with the highest quartile have low synthesis and high absorption in both adolescence and later in young adult life.

PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment.

BACKGROUND: In mild cognitive impairment (MCI), Alzheimer's disease (AD)-type cerebrospinal fluid (CSF) biomarker profiles predict rapid progression and conversion to AD. An increased brain amyloid burden in AD and MCI has been demonstrated with PET using [(11)C]PIB (Pittsburgh compound B). Little is known about the relationship between these biomarkers in MCI. METHODS: We studied 15 patients with amnestic MCI and 22 controls with PET using [(11)C]PIB. In MCI patients, CSF levels of Abeta42, pTAU, totalTAU and the Abeta42/pTAU ratio were measured. RESULTS: In MCI patients, CSF Abeta42 was abnormal in 53% of patients, totalTAU in 67%, pTAU in 64% and the Abeta42/pTAU ratio in 64%. A composite neocortical [(11)C]PIB uptake score was increased in 87% of the MCI patients. Only 54% of [(11)C]PIB-positive subjects showed AD-type Abeta42 values. During a 2-year follow-up, 6 MCI patients converted to AD, all of them had increased neocortical PIB scores at the MCI stage. Abnormal CSF Abeta42 was found in 3 patients, pTAU in 3 patients and Abeta42/pTAU ratio in 4 patients. CONCLUSION: Follow-up studies are needed to confirm whether [(11)C]PIB uptake might be more sensitive than CSF Abeta42 concentration in detecting increased amyloid burden in MCI, as suggested by the results of this study.

Apolipoprotein E epsilon 4 allele is associated with increased atrophy in progressive mild cognitive impairment: a voxel-based morphometric study.

BACKGROUND: The apolipoprotein E (APOE) epsilon4 allele is a risk factor for Alzheimer's disease. Earlier studies have shown differences in brain structure according to the APOE epsilon4 status. OBJECTIVE: To assess possible differences in brain structure according to the APOE epsilon4 status in mild cognitive impairment (MCI) subjects in relation to conversion to dementia. METHODS: In a follow-up study of 56 MCI subjects, 13 MCI subjects progressed to dementia (PMCI) during a mean follow-up time of 31 months. Brain structure differences in both stable MCI (SMCI) and PMCI epsilon4 carriers and noncarriers in the baseline MRI scan were assessed with voxel-based morphometry. RESULTS: The SMCI epsilon4 carriers had atrophy in the amygdala and hippocampus compared to the SMCI noncarriers. The PMCI epsilon4 carriers revealed atrophy of the left inferior frontal gyrus and parietal cortex compared to the PMCI noncarriers. CONCLUSION: The rate of brain atrophy in certain brain areas may be increased in epsilon4-positive MCI subjects progressing to dementia.

Moderate increase in dietary sucrose does not influence fasting or postprandial serum lipids regardless of the presence of apolipoprotein E2 allele in healthy subjects.

OBJECTIVE: To investigate whether a moderate increase in dietary sucrose intake induces different serum lipid responses in normolipidemic subjects with the epsilon 2 allele compared with subjects without the epsilon 2 allele. DESIGN: Controlled, parallel study. SUBJECTS: There were 15 subjects with the apolipoprotein E (APOE)3/2 genotype and 19 subjects with the APOE 3/3 or 3/4 genotype, whose mean+/-s.d. age was 48+/-14 and 35+/-10 years, respectively. All subjects had normal glucose metabolism. INTERVENTIONS: The subjects were instructed to increase their sucrose intake by 40 g/day for 8 weeks and to decrease the intake of saturated and unsaturated fat to maintain energy balance. Dietary adherence was monitored using food records and the actual increase in sucrose intake was 39.8+/-18.4 g/day. Sixteen subjects (nine with APOE 3/2 genotype, seven with APOE 3/3 or 3/4 genotypes) participated also in an 8 h oral fat tolerance test at the beginning and at the end of the intervention. RESULTS: Body weight remained stable during the intervention. Sucrose intake did not have a significant effect on fasting concentrations of serum total and lipoprotein lipids, plasma glucose, serum insulin, squalene and non-cholesterol sterols in either genotype group. Neither were there any changes in postprandial lipid or insulin responses. CONCLUSIONS: Moderate increase in sucrose intake does not affect fasting or postprandial serum lipid responses in healthy subjects with or without the epsilon 2 allele.

Ester percentages of plant sterols and cholesterol in chylomicrons and VLDL of humans with low and high sterol absorption.

Ester percentages of cholesterol and non-cholesterol sterols were measured in chylomicrons and very low density lipoproteins (VLDL) in 15 subjects. Our hypothesis was that in humans, in contrast to animal experiments, plant sterols in chylomicrons are esterified similarly to cholesterol. In fact, the mean ester percentage of chylomicron sitosterol (approximately 40%), but not of campesterol ( approximately 51%), was lower than that of cholesterol (approximately 54%) in the whole study population. In high cholesterol absorbers (high serum total campesterol, > or = 2.8 mmol/mol of cholesterol), the ester percentages of sitosterol and other non-cholesterol sterols were similar to that of cholesterol in chylomicrons, and the percentages tended to be higher than those in low absorbers. In contrast to chylomicrons, the ester percentages of sterols in VLDL tended to be lower in the high than low absorbers. In conclusion, percentages of plant sterol esters are not consistently lower than those of cholesterol in chylomicrons.

Postprandial behavior of plasma squalene and non-cholesterol sterols in men with varying cholesterol absorption.

BACKGROUND: The purpose of this study was to investigate, whether low vs. high absorption of cholesterol affects the postprandial lipid clearance (squalene as the surrogate marker) and postprandial cholesterol metabolism evaluated with plasma levels of cholesterol absorption (cholestanol and plant sterols) and synthesis markers (desmosterol and lathosterol). METHODS: Fifteen normo- or mildly hypercholesterolemic men were divided into low or high cholesterol absorbers on the basis of plasma cholestanol to cholesterol ratio and they volunteered to an oral fat load test containing fat 35 g/m(2) body surface. RESULTS: Plasma squalene to cholesterol ratio did not differ between the groups throughout the postprandial follow-up of 8 h. The level differences in the plasma absorption and synthesis markers seen at baseline remained between the groups, so that in high absorbers the absorption markers remained high and synthesis markers low throughout the postprandial follow-up. The postprandial response curves of desmosterol (p<0.05) and lathosterol (p=0.052) to cholestanol decreased linearly in the low, but not in the high absorbers. CONCLUSIONS: Low vs. high absorption of cholesterol does not affect the first 8-h postprandial lipid clearance. The metabolic profile of cholesterol is maintained postprandially. The postprandial decrease in cholesterol synthesis differs in low vs. high absorbers especially through the desmosterol pathway.

MR T2 relaxometry in Alzheimer's disease and age-associated memory impairment.

A prolonged MR T2 relaxation time was proposed to mark the presence and severity of Alzheimer's disease (AD). We studied the value of T2 relaxometry in diagnosing early AD. T2 was measured from 54 patients with AD, 25 subjects with age-associated memory impairment (AAMI), 18 elderly and 16 young controls. The AD patients had longer T2 in the right hippocampal head (104 +/- 11 ms) and tail (98 +/- 10 ms) than age-matched controls (95 +/- 5 and 92 +/- 9 ms, respectively). This prolongation was not related to age. In the AD group, the T2 of the left hippocampal head also correlated with the clinical severity. The T2 of the amygdala did not differ across the groups. Increased T2 in the temporal and parietal white matter and the thalamus related to increasing age rather than to the diagnostic category. The AAMI subjects had T2 comparable with those of age-matched controls. Despite the prolongation of T2 in the AD group the possible diagnostic value was compromized by a substantial overlap between the study groups. We, thus, conclude that the T2 relaxometry is not a reliable method for diagnosing early AD.

MRI of the hippocampus in Alzheimer's disease: sensitivity, specificity, and analysis of the incorrectly classified subjects.

In this study, magnetic resonance imaging (MRI) of the hippocampus for the diagnosis of early Alzheimer's disease (AD) is evaluated. We measured hippocampal volumes and the area of the medial hippocampus with a 1.5 T MR imager in 160 subjects: 55 patients with probable AD according to the NINCDS-ADRDA criteria, 43 subjects fulfilling the NIMH criteria of age-associated memory impairment (AAMI), 42 cognitively normal elderly controls, and 20 controls younger than 50 years. Three methods for normalization were compared. The hippocampi were atrophied in the AD patients, but not in the AAMI subjects or the elderly controls. There was no significant correlation between hippocampal volumes and age in the nondemented subjects. The discrimination based on volumetry resulted in an overall correct classification of 92% of AD patients vs. nondemented elderly subjects, whereas discrimination based on hippocampal area was less accurate, producing a correct classification in 80% of the subjects. We conclude that the hippocampus as assessed by MRI volumetry is atrophied early in AD, and spared by aging or AAMI. A brief critical review of previous studies is in concordance with the presented data: all the previous studies that have used volumetry, have similarly ended up with a good classification, whereas simpler or subjective measurements, subject to various sources of bias, have produced most variable results.

Effects of 2 low-fat stanol ester-containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects.

BACKGROUND: Full-fat sitostanol ester-containing margarine reduces serum total and LDL cholesterol, but the effect of plant stanol ester-containing margarine as part of a low-fat, low-cholesterol diet has not been studied. OBJECTIVE: We investigated the cholesterol-lowering effects of 2 novel, low-fat stanol ester-containing margarines as part of a low-fat diet recommended for hypercholesterolemic subjects. DESIGN: In a parallel, double-blind study, 55 hypercholesterolemic subjects were randomly assigned after a 4-wk high-fat diet (baseline) to 3 low-fat margarine groups: wood stanol ester-containing margarine (WSEM), vegetable oil stanol ester-containing margarine (VOSEM), and control margarine (no stanol esters). The groups consumed the margarines for 8 wk as part of a diet resembling that of the National Cholesterol Education Program's Step II diet. The daily mean total stanol intake was 2.31 and 2.16 g in the WSEM and VOSEM groups, respectively. RESULTS: During the experimental period, the reduction in serum total cholesterol was 10.6% (P < 0.001) and 8.1% (P < 0.05) greater and in LDL cholesterol was 13.7% (P < 0.01) and 8.6% (P = 0.072) greater in the WSEM and VOSEM groups, respectively, than in the control group. Serum campesterol concentrations decreased 34.5% and 41.3% (P < 0.001) in the WSEM and VOSEM groups, respectively. Serum HDL cholesterol, sitostanol, campestanol, beta-carotene, and fat-soluble vitamin concentrations did not change significantly from baseline. CONCLUSIONS: We conclude that the low-fat, plant stanol ester-containing margarines are effective cholesterol-lowering products in hypercholesterolemic subjects when used as part of a low-fat, low-cholesterol diet. They offer an additional, clinically significant reduction in serum cholesterol concentrations to that obtained with a low-fat diet alone.

Decline of frontal lobe functions in subjects with age-associated memory impairment.

OBJECTIVE: To assess frontal lobe functions of subjects with age-associated memory impairment (AAMI) and to examine whether performance on neuropsychological tests is correlated with the volume of the frontal lobes in magnetic resonance imaging. DESIGN: Cross-sectional two-group comparison. SETTING: The Memory Research Clinic of Kuopio University and the Magnetic Resonance Imaging Center of Kuopio University Hospital. PARTICIPANTS: Ninety subjects (mean age, 70.5 years), 43 with AAMI diagnosed according to National Institute of Mental Health criteria and 47 age-matched healthy controls. MEASUREMENTS: Four neuropsychological tests were used to assess frontal lobe function: Verbal Fluency Test (VFT), Modified Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Stroop Test (ST). A 1.5-T magnetic resonance imager was used for volume measurements. RESULTS: The AAMI subjects scored significantly worse on the WCST, ST, and TMT compared with controls (ANCOVA, adjusted for age and education, p < 0.05). The frontal lobe volumes did not differ between AAMI subjects and controls. CONCLUSIONS: AAMI subjects appear to be impaired not only in tests assessing memory but also in tests of executive functions. This finding agrees with previous reports suggesting a central role for frontal dysfunction in memory loss of elderly people.

Hippocampal volumes in Alzheimer's disease, Parkinson's disease with and without dementia, and in vascular dementia: An MRI study.

Hippocampal atrophy detected by volumetric MRI is a sensitive feature of early Alzheimer's disease (AD), but there are no studies evaluating hippocampal atrophy by MR volumetry in other dementing diseases. We therefore compared hippocampal volumes in a total of 113 subjects: 50 patients with mild to moderate AD, 9 patients with vascular dementia (VaD), 12 patients with idiopathic Parkinson's disease (PD) without dementia, 8 patients with PD and dementia (PDD), and 34 elderly control subjects. Thin, coronal, contiguous images were obtained by a 1.5-T MR imager. All patient groups had significantly smaller volumes of the hippocampus compared with the control group. In the PDD group, the absolute volumes were even smaller than in the AD group. In the PD group, the volumes were diminished to a lesser but significant extent. The volumes in the VaD group varied: of nine patients, two had no atrophy, three had unilateral, and four had bilateral atrophy. We postulate that hippocampal atrophy does not seem to be a specific phenomenon of dementia in AD but also occurs in VaD and PDD, and even in PD when no dementia is present. However, coexistence of AD pathology in our PD and VaD patients cannot be ruled out. Further studies with access to neuropathologic data are needed.

Volumetric MRI analysis of the amygdala and the hippocampus in subjects with age-associated memory impairment: correlation to visual and verbal memory.

Age-associated memory impairment (AAMI) is a common but disputed entity. It is unclear whether AAMI is a phenomenon of normal aging or an early sign of Alzheimer's disease. The present study aimed to identify possible structural abnormalities in the medial temporal lobe of AAMI subjects. We measured volumes of the hippocampus and amygdala by MRI in 16 AAMI subjects and in 16 age- and sex-matched controls and correlated the volumes with subjects' performance on two visual memory tasks (the Benton and the Heaton visual retention tests) and on a verbal memory task (the Buschke-Fuld Selective Reminding Test). The mean hippocampal and amygdaloid volumes normalized for brain size per se did not differ between the two study groups. In controls, but not in AAMI subjects, the right hippocampus was larger than the left. Accordingly, the volumetric asymmetry between the right and left hippocampi was smaller in AAMI subjects than in controls (Student's t test, p < 0.05). The volume of the right hippocampus (r = 0.37, n = 32, p < 0.05) and the magnitude of the asymmetry between the right and left hippocampi (r = 0.38, n = 32, p < 0.05) correlated with total score on the Benton test. We also found significant correlations between the amygdaloid volumes and the performance on visual memory tests but not with score on the verbal memory test.(ABSTRACT TRUNCATED AT 250 WORDS)

Midlife income, occupation, APOE status, and dementia: a population-based study.

OBJECTIVE: To examine the relationship between socioeconomic factors and APOE carrier status on the development of dementia. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1449 (73%) subjects aged 65 to 79 years were re-examined in 1998. The diagnosis of dementia among the nonparticipants was derived from patient records of the local hospitals and primary health care clinics. RESULTS: Low income level at old age was related to dementia, but low income level at midlife was not a risk factor for dementia. Dementia was also associated with decreasing income level, from midlife to old age 21 years later, when dementia was diagnosed. A sedentary occupation (office, service, or intellectual work) was associated with a decreased risk for dementia among participants; however, when the nonparticipants were included in the analysis, the associations were no longer significant. Low educational level and the APOE epsilon4 allele independently increased the risk for dementia. CONCLUSIONS: Reduction in income level during follow-up and low income level at old age might be the consequence of a dementing process rather than being associated with risk evolution of dementia.

Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study.

OBJECTIVE: To evaluate the impact of midlife elevated serum cholesterol levels and blood pressure on the subsequent development of mild cognitive impairment (MCI) and to investigate the prevalence of MCI in elderly Finnish population, applying the MCI criteria devised by the Mayo Clinic Alzheimer's Disease Research Center. BACKGROUND: MCI has been considered as a predictor of AD. Vascular risk factors may be important in the development of cognitive impairment and AD. However, the role of vascular risk factors in MCI and the prevalence of MCI still remain virtually unknown. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1,449 subjects aged 65 to 79 years were reexamined in 1998. RESULTS: Eighty-two subjects, 6.1% of the population (average age, 72 years) met the criteria for MCI. Midlife elevated serum cholesterol level (> or =6.5 mmol/L) was a significant risk factor for MCI (OR, 1.9; 95% CI, 1.2 to 3.0, adjusted for age and body mass index); the effect of systolic blood pressure approached significance. CONCLUSION: Data point to a role for midlife vascular risk factors in the development of MCI in late life.

Diagnosis of Alzheimer's disease: MRI of the hippocampus vs delayed recall.

Hippocampal volume measurements using magnetic resonance imaging (MRI) and assessment of performance in tests of delayed recall are among the most useful aids for diagnosing early Alzheimer's disease (AD) on an individual level. However, their comparative diagnostic accuracy has not been previously addressed. In this study we compared the diagnostic accuracy of these two methods in 57 patients with probable AD according to the NINCDS-ADRDA criteria, and 34 age- and gender-matched control subjects. The discriminatory power of the hippocampal volumes and delayed recall performance, Russel's Adaptation of the Visual Reproduction Test (VRT), were compared in discrimination function and receiver operator characteristic analyses. Right and left hippocampal volumes resulted in correct classification of 85.7-86.8% of the study subjects, respectively, while performance in the VRT resulted in correct classification of 93.4% of subjects. The area under curve value was 0.93 for the left hippocampus and 0.96 for the VRT. These data suggest that assessment of delayed recall with the VRT is of high diagnostic accuracy, and may surpass the diagnostic accuracy of hippocampal volumetry.

A follow-up study of age-associated memory impairment: neuropsychological predictors of dementia.

OBJECTIVE: To examine the clinical course of age-associated memory impairment (AAMI) and to evaluate the value of neuropsychological tests in predicting cognitive decline in AAMI subjects in a follow-up period of more than 3 years. DESIGN: Prospective cohort study. SETTING: The outpatient Memory Research Unit of the Department of Neurology at the University of Kuopio in Eastern Finland. PARTICIPANTS: A sample of 229 subjects (mean age 71.7 years) identified in two screening studies as having AAMI. MEASUREMENTS: A battery of neuropsychological tests and a structured inquiry for health status and subjective memory complaints were performed at baseline and follow-up to diagnose AAMI according to the criteria proposed by a National Institute of Mental Health work group. RESULTS: Of the 229 subjects, 176 (76.9%) participated in the follow-up for, on average, 3.6 years after the baseline. Of the participants, 104 (59.1%) still met the AAMI criteria. Other subjects were classified into five subgroups: (1) subjects showing decline in cognition meeting dementia diagnosis (16, 9.1% (13 of them AD)); (2) subjects with mild cognitive decline meeting neither dementia nor AAMI criteria (13, 7.4%); (3) subjects with memory performance now superior to AAMI criteria (17, 9.7%); (4) subjects having a disease classified as exclusion in the criteria (15, 8.5%); (5) subjects not now reporting subjective memory loss in everyday life (9, 5.1%). Two subjects (1.1%) were not classified because of incomplete data. Neuropsychological tests predicted which subjects would develop dementia during the follow-up period. The best discriminators between these subjects and those who remained AAMI were memory and verbal fluency tests. CONCLUSION: The study suggests that, in general, AAMI is nonprogressive, but the AAMI population also includes subjects with early dementia and subjects without genuine memory loss. However, these subjects can be differentiated with a more detailed neuropsychological evaluation.