Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients

Alzheimer's disease (AD) is characterized by the presence of senile plaques, neurofibrillary tangles, and neuronal cell loss associated with membrane cholesterol release. 24S-hydroxycholesterol (24S-OH-Chol) is an enzymatically oxidized product of cholesterol mainly synthesized in the brain. We tested the hypothesis that plasma levels of this oxysterol could be used as a putative biochemical marker for an altered cholesterol homeostasis in the brain of AD patients. Thirty patients with clinical criteria for AD, 30 healthy volunteers, 18 depressed patients, and 12 patients with vascular dementia (non-Alzheimer demented) were studied. Plasma concentrations of 24S-OH-Chol were assayed by isotope dilution;-mass spectrometry, cholesterol was measured enzymatically, and apolipoprotein E (apoE) was genotyped by polymerase chain reaction and restricted fragment length polymorphism. The concentration of 24S-OH-Chol in AD and non-Alzheimer demented patients was modestly but significantly higher than in healthy controls and in depressed patients. There was no significant difference in the concentrations of 24S-OH-Chol between depressed patients and healthy controls nor between AD and non-Alzheimer demented patients. The apoE straightepsilon4 allele influences plasma 24S-OH-Chol. However, this influence could be completely accounted for by the elevated plasma cholesterol in apoE4 hetero- or homozygotes. Plasma 24S-OH-Chol levels correlated negatively with the severity of dementia. AD and vascular demented patients appear to have higher circulating levels of 24S-OH-Chol than depressed patients and healthy controls. We speculate that 24S-OH-Chol plasma levels may potentially be used as an early biochemical marker for an altered cholesterol homeostasis in the central nervous system. 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients.     

Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: population based study.

OBJECTIVE--To determine the association between the e4 allele of apolipoprotein E and Alzheimer''s disease in a randomly selected population sample. DESIGN--Cross sectional population based study. SUBJECTS--980 people aged 69 to 78 (349 men, 631 women). SETTING--Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES--Presence of e4 allele and diagnosis of Alzheimer''s disease by detailed neurological and neurophysiological evaluation. RESULTS--46 (4.7%) subjects were classified as having probable or possible Alzheimer''s disease. The frequency of the apolipoprotein E e4 allele was 0.359 in patients with Alzheimer''s disease and 0.165 subjects without dementia (P < 0.0001). The prevalence of Alzheimer''s disease was 2.9% in subjects with no e4 alleles, 7.6% in subjects with one e4 allele, and 21.4% in subjects with two e4 alleles of apolipoprotein E. CONCLUSIONS--Allele e4 of apolipoprotein is associated with Alzheimer''s disease in a dose-response fashion in a randomly selected elderly population.     

Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study.

OBJECTIVE--To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. DESIGN--Population based cross sectional study. SETTING--Ommoord, a suburb of Rotterdam. SUBJECTS--7528 participants of the Rotterdam study aged 55-106 years. RESULTS--474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimer''s disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinson''s disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. CONCLUSIONS--The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimer''s disease. In this study an inverse dose-response relation was found between education and dementia--in particular, Alzheimer''s disease.     

Occludin is overexpressed in Alzheimer's disease and vascular dementia

The tight junctions (TJs) are key players in the control of blood-brain barrier (BBB) properties, the most complex TJs in the vascular system being found in the endothelial cells of brain capillaries. One of the main TJs proteins is occludin, which anchors plasma membranes of neighbour cells and is present in large amounts in the brain endothelia. Previous studies demonstrated that disruption of BBB in various pathological situations associates with changes in occludin expression, and this change could be responsible for malfunction of BBB. Therefore in this study, applying an immunohistochemical approach, we decided to explore the occludin expression in frontal cortex (FC) and basal ganglia in ageing control, Alzheimer's disease (AD), and vascular dementia (VD) brains, as far as all these pathologies associate microangiopathy and disruption of BBB. Strikingly, we found selected neurons, astrocytes and oligodendrocytes expressing occludin, in all cases studied. To estimate the number of occludin-expressing neurons, we applied a stereological approach with random systematic sampling and the unbiased optical fractionator method. We report here a significant increase in ratio of occludin-expressing neurons in FC and basal ganglia regions in both AD and VD as compared to ageing controls. Within the cerebral cortex, occludin was selectively expressed by pyramidal neurons, which are the ones responsible for cognitive processes and affected by AD pathology. Our findings could be important in unravelling new pathogenic pathways in dementia disorders and new functions of occludin and TJs.     

Plasma sorbitol dehydrogenase in diabetic subjects with or without vascular complications

Plasma Sorbitol Dehydrogenase levels were determined in subjects with diabetes mellitus and normal people. The diabetic subjects had circulating plasma levels of SDH significantly higher (p less than 0.001) than those observed in controls. Moreover, the diabetics with vascular complications presented the highest SDH values. The lack of positive correlation between plasma glucose and SDH levels suggests that SDH, like hemoglobin A1C, reflect the degree of previous metabolic control of diabetes mellitus.     

Lack of association between vascular dementia and Chlamydia pneumoniae infection: a case-control study

Background

Chronic inflammation appears to play a role in the pathogenesis of vascular dementia. Given the association between Chlamydia pneumoniae and stroke, the possibility exists that previous exposure to C. pneumoniae may play a role in vascular dementia. The objective of this study was to determine if there was an association between serological evidence of C. pneumoniae infection or inflammatory markers with vascular dementia.

Methods

28 case-patients with vascular dementia at a geriatric clinic and 24 caregiver-controls were tested for C. pneumoniae IgG and IgA antibodies. The association between vascular dementia and C. pneumoniae titres as well as inflammatory markers was estimated by using both conditional logistic regression and stratified logistic regression.

Results

When matched cases were compared to controls, there was no significant difference in elevated C. pneumoniae specific IgG antibodies (titre ≥ 1:32), odds ratio [OR] 1.3 (95% confidence intervals [CI] 0.3 to 6.0), p = 0.71, or in elevated C. pneumoniae specific IgA antibodies (titre ≥ 1:16), OR 2.0 (95%CI 0.5 to 8.0), p = 0.33 indicative of past or persistent C. pneumoniae infection. Similarly, no difference in high IgG or IgA antibody levels (IgG titre ≥ 1:512 or IgA titre ≥ 1:64) between the two groups, indicative of recent C. pneumoniae infection, was found, OR 0.4 (95%CI 0.1 to 2.1), p = 0.27. For C-reactive protein (CRP), the mean difference between 18 matched pairs (case – control) was – 3.33 mg/L. There was no significant difference between cases and controls when comparing log transformed values, OR 0.03 (95%CI 0.00 to 2.89), p = 0.13 or comparing CRP values above or below the median, OR 0.8 (95%CI 0.2 to 3.4), p = 0.71. For fibrinogen, the mean difference between pairs (case – control) was -0.07 g/L. There was no statistical difference between cases and controls when comparing log transformed values, OR 0.6 (95%CI 0.0 to 31.2), p = 0.79 or between fibrinogen values above and below the median, OR = 0.5 (95%CI 0.1 to 2.0), p = 0.50.

Conclusion

We found no evidence for a significant association between C. pneumoniae infection, inflammatory markers such as CRP and fibrinogen, and vascular dementia.

     

The association of a cystatin C gene polymorphism with late-onset Alzheimer's disease and vascular dementia

A polymorphism in the cystatin C (CST3) gene was suggested to associate with Alzheimer's disease (AD). In the present study we attempted to determine the association between CST3 polymorphism and AD or vascular dementia (VD), and whether such effects are dependent of the APOE4 allele. The polymorphisms of CST3 genotype were determined using polymerase chain reactions (PCR) followed by gel electrophoresis in 124 AD, 70 VD, and 115 control individuals. No statistical difference in CST3B allele frequencies was observed among all three groups. Associations between CST3B/B genotype and AD patients older than 75-year-old, or VD patients younger than 75-year-old were evident. The APOE4 allele alone significantly increased the odds for the developing AD, but not VD. A logistic regression analysis revealed that either CST3 or its interaction with APOE4 were not significant predictors of AD. However, a synergistic association of CST3 and APOE4 alleles was observed in predicting VD patients. These results suggest that CST3 might interact with APOE4 on conferring vascular pathologies.     

"Closing-in" phenomenon in Alzheimer's disease and subcortical vascular dementia

Background  

The 'closing-in' phenomenon is defined as a tendency to close in on a model while copying it. This is one of several constructional apraxia observed in dementia, particularly in Alzheimer's disease (AD). The aim of this study was to investigate the usefulness of it in the differential diagnosis of AD and subcortical vascular dementia (SVD) and to clarify the factors associated with it.     

Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease

A cholesterol-rich emulsion (LDE) that resembles the LDL lipidic structure is taken-up by LDL receptors after intravenous injection by means of apolipoprotein E it acquires in the circulation and can be used to probe LDL metabolism. In this study, LDE was labeled with [14C]cholesteryl oleate and [3H]cholesterol and injected into 19 patients with coronary artery disease (CAD) and into 14 subjects without CAD to verify whether the kinetic behavior of the radioactive lipids is different in CAD. Blood was sampled over 24 h for radioactivity measurement after lipid extraction and separation by thin-layer chromatography. Fractional clearance rate (FCR, in h-1) of [14C]cholesteryl ester was not different in CAD and nonCAD expressed as median (25%; 75%): 0.08 (0.062; 0.134) h-1 versus 0.06 (0.04; 0.083) h-1, P = 0.167. However, [3H]cholesterol FCR was greater in CAD than in nonCAD (mean +/- SEM): 0.163 +/- 0.016 h-1 versus 0.077 +/- 0.014 h-1, P < 0.001. Esterification of the LDE [3H]cholesterol was also greater in CAD subjects than nonCAD at 10 h and 24 h after emulsion injection (P = 0.029 and 0.024 respectively). In conclusion, both removal from the plasma and esterification of the LDE-cholesterol were increased in CAD. These findings may contribute for unraveling pro-atherogenic mechanisms and the establishment of novel CAD markers.     

Cerebrospinal fluid markers in differential diagnosis of Alzheimer's disease and vascular dementia

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common causes of dementia in old people. They remain difficult to differentiate in practice because of lack of sensitivity and specificity of current clinical diagnostic criteria. Recent molecular and cellular advancements indicate that the use of cerebrospinal fluid markers may improve early detection and differential diagnosis of AD. Our objective in this study was to determine diagnostic accuracy of three cerebrospinal (CSF) markers: total tau protein (t-tau), tau protein phosphorylated on threonine 181 (p-tau181) and tau protein phosphorylated on serine 199 (p-tau199). Using commercially available ELISA kits concentrations of t-tau, p-tau181 and p-tau199 were analyzed in 12 patients with probable AD, 9 patients with VaD and 12 NC subjects. The median levels of all three markers were significantly higher in AD group versus VaD and NC groups. However, when the sensitivity levels were set to 85% or higher, only t-tau and p-tau199 satisfied consensus recommendations (specificity more than 75%) when differentiating AD from VaD. In conclusion, our preliminary data on a small group of selected subjects suggest that the CSF t-tau and p-tau199 levels are useful markers for differentiating AD from VaD.     

Shift in brain metabolism in late onset Alzheimer's disease: implications for biomarkers and therapeutic interventions

Alzheimer's is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. Increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. Compromised mitochondrial bioenergetics lead to over-production of and mitochondrial accumulation of β-amyloid, which is coupled with oxidative stress. Collectively, this results in a shift in brain metabolic profile from glucose-driven bioenergetics towards a compensatory, but less efficient, ketogenic pathway. We propose that the compensatory shift from a primarily aerobic glycolysis pathway to a ketogenic/fatty acid β-oxidation pathway eventually leads to white matter degeneration. The essential role of mitochondrial bioenergetics and the unique trajectory of compensatory metabolic adaptations in brain enable a bioenergetic-centric strategy for development of biomarkers. From a therapeutic perspective, this trajectory of alterations in brain metabolic capacity enables disease-stage specific strategies to target brain metabolism for disease prevention and treatment. A combination of nutraceutical and pharmaceutical interventions that enhance glucose-driven metabolic activity and potentiate mitochondrial bioenergetic function could prevent the antecedent decline in brain glucose metabolism, promote healthy aging and prevent AD. Alternatively, during the prodromal incipient phase of AD, sustained activation of ketogenic metabolic pathways coupled with supplementation of the alternative fuel source, ketone bodies, could sustain mitochondrial bioenergetic function to prevent or delay further progression of the disease.     

Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control study

Background

A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near MS4A4A, CD2AP, EPHA1 and CD33. Meta-analyses of this and a previously published GWAS revealed significant association at ABCA7 and MS4A, independent evidence for association of CD2AP, CD33 and EPHA1 and an opposing yet significant association of a variant near ARID5B. In this study, we genotyped five variants (in or near CD2AP, EPHA1, ARID5B, and CD33) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE ε4 dosage.

Results

We found no significant evidence of series heterogeneity. Associations with LOAD were successfully replicated for EPHA1 (rs11767557; OR = 0.87, p = 5 × 10^-4) and CD33 (rs3865444; OR = 0.92, p = 0.049), with odds ratios comparable to those previously reported. Although the two ARID5B variants (rs2588969 and rs494288) showed significant association with LOAD in meta-analysis of our dataset (p = 0.046 and 0.008, respectively), the associations did not survive adjustment for covariates (p = 0.30 and 0.11, respectively). We had insufficient evidence in our data to support the association of the CD2AP variant (rs9349407, p = 0.56).

Conclusions

Our data overwhelmingly support the association of EPHA1 and CD33 variants with LOAD risk: addition of our data to the results previously reported (total n > 42,000) increased the strength of evidence for these variants, providing impressive p-values of 2.1 × 10^-15 (EPHA1) and 1.8 × 10^-13 (CD33).     

Cadmium in blood in Alzheimer's disease and non-demented subjects: results from a population-based study

Blood cadmium concentrations were studied in Alzheimer's disease (AD) and non-demented subjects. The 29 individuals were randomized from the ongoing population survey on ageing and dementia in Stockholm, the Kungsholmen Project. Smokers had, as expected, higher cadmium levels than non-smokers. Cadmium concentrations in blood were related to diastolic blood pressure in non-smoking, non-demented individuals. In contrast to previous reports no differences in blood cadmium levels were found between AD sufferers and non-demented subjects. Furthermore, there were no correlations between cadmium levels in blood and age or cognitive functions. The importance of quality assurance in sample collection and analysis of cadmium as well as scrutinizing smoking habits is emphasized.     

Animal models for Alzheimer's disease and frontotemporal dementia: a perspective

In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer''s disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as diverse as mice, fish, flies and worms. Advances in imaging and therapy are explored. We also discuss some anticipated new models and developments. These will reveal how key players in the pathogenesis of Alzheimer''s disease and frontotemporal dementia, such as the peptide Aβ (amyloid β) and the protein tau, cause neuronal dysfunction and eventually, neuronal demise. Understanding these processes fully will lead to early diagnosis and therapy.     

Neuropeptides in Alzheimer's disease: a postmortem study

The concentration of 5 neuropeptides, neurotensin (NT), somatostatin (SRIF), corticotropin-releasing factor (CRF), bombesin and thyrotropin-releasing hormone (TRH) was measured in 3 cerebrocortical areas and several subcortical regions in post-mortem brains obtained from patients with histologically verified Alzheimer's disease and from controls without neurological or psychiatric disorders using sensitive and specific radioimmunoassay procedures. In Alzheimer's disease, reductions in the concentration of SRIF and CRF were observed in frontal and temporal cortex. In addition, in Alzheimer's disease, SRIF was also reduced in concentration in the hypothalamus, whereas CRF concentrations were reduced in the caudate nucleus. Neurotensin was reduced in concentration in the amygdala in Alzheimer's disease. No alterations in TRH or bombesin/gastrin-releasing peptide were found. These findings provide further evidence for the pathological involvement of certain neuropeptide-containing neurons in Alzheimer's disease.     

Salivary levels of mutans streptococci associated with restorations: a case-control study

Our aim was to estimate whether restorative therapy with amalgam and composite resin could decrease salivary mutans streptococcal level, thus also decreasing the risk for other caries development. We selected a case group of 93 children with detectable salivary mutans levels (i.e., at least 1x10(4) cfu/ml), and a control group (n=93 subjects) with undetectable levels. Children had the same age (12 years), no extracted teeth, crowns, temporary fillings, and restorations other than amalgam and composite resin, and the two groups had similar gender distribution. We clinically examined children and recorded active caries, restorations and oral hygiene level by means of gingival bleeding on probing; we also investigated sucrose intake at breakfast. The case group had statistically significant higher prevalence of restorations (36.6% vs. 18.3%), active caries (44.1% vs. 12.9%), and bad oral hygiene (84.9% vs. 68.8%) than the control group. However, the logistic regression analysis showed that presence of active caries was the only significant variable associated with mutans streptococci (OR=4.0; p=0.0002), while the effects of sucrose intake and of restorations were marginally significant. This apparent contrast between statistical analyses was due to the concomitant presence, in children with detectable mutans streptococci level, of restorations and decayed teeth at the same time, and, on the basis of the multivariate analysis, presence of mutans streptococci in these children was explained by the presence of active caries, more than restorations.     

NXX-066 in patients with Alzheimer's disease: a bridging study

Reduced cholinergic transmission is a key neurotransmitter dysfunction in Alzheimer's Disease (AD). NXX-066, a physostigmine analog and acetylcholinesterase (AChE) inhibitor, has demonstrated activity in animal models of memory function, and was well tolerated in healthy subjects up to a single dose of 64 mg and multiple doses of 60 mg QD for seven days. Since AChE inhibitors are often tolerated differently in AD patients than in healthy volunteers, a randomized, placebo-controlled, double-blind, single-center, inpatient bridging study was conducted to determine the maximum tolerated dose (MTD) of NXX-066 in the target patient population. Seven consecutive panels of eight AD patients each (6 active, 2 placebo) received fixed oral doses of NXX-066 (20, 30, 40, 50, 60, 70, or 80 mg BID) for seven days. Initiation of each subsequent panel (dose group) was contingent upon the tolerability of lower dose levels. The MTD was determined to be 70 mg BID when four of six patients receiving 80 mg BID were prematurely discontinued from the study due to nausea and/or vomiting, accompanied in some patients by mild to moderate dizziness, headache, asthenia, and gastric symptoms. Wide variability in plasma levels of NXX-066 was observed in all dose panels. AChE inhibition in whole blood correlated with both maximum plasma concentration and dose; however, AChE inhibition was not predictive of adverse events. In this study, AD patients tolerated larger daily doses of NXX-066 on a BID regimen than healthy normal subjects had tolerated with QD dosing. Further studies are warranted to examine whether differing tolerability between patients and healthy subjects or the reduced dosing interval explains these findings.     

Physostigmine effects in Alzheimer's disease: relationship to dementia severity

Eleven demented patients were administered .004, .009, and .013 mg/kg physostigmine intramuscularly, and placebo, double-blind, in Phase 1. The most effective dose, in terms of showing the best memory score as compared to saline, was repeated during Phase 2. Five patients improved their verbal memory scores in both Phases 1 and 2 after the most effective dose of physostigmine; these five "responders" were found to be significantly more demented than the six "nonresponders." Drug-induced increases in memory scores were significantly correlated with illness severity. Intrusions, which were not a factor in selection of the most effective dose, were reduced in the group as a whole, with the responders showing the most improvement and the nonresponders the least. The association between physostigmine effect and degree of dementia suggests to us that the severe cases may have more permeable blood-brain barriers, and that drug availability to the brain is an important factor in evaluating treatment of SDAT with cholinergic substances.     

Serum lipid levels in patients with Alzheimer's disease

The role of lipids in the aetiology and progress of Alzheimer's disease (AD) is still unclear High lipid levels could be one of the risk factors for AD, but no association or even protective effects of high cholesterol levels in the development of the AD were also found. The aim of the study was to determine serum levels of total cholesterol, high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C) and triglycerides (TG) in female patients with AD and in healthy elderly controls. The 50 patients met the diagnostic criteria of probable AD according to the NINDS-ADRDA and DSM-IV criteria. Cognitive impairment was evaluated using the Mini Mental State Examination (MMSE). Patients were subdivided into two groups of 19 patients in the middle (MMSE 10-19) and 31 patients in the late (MMSE 0-9) phase ofAD. Psychotic and non-psychotic features, evaluated by means of Neuropsychiatric Inventory, were presented in 13 and 37patients with AD, respectively. Control group consisted of 58 subjects without cognitive impairment (MMSE >27) and with lipid levels within normal range. Serum lipid levels were determined by the enzymatic colour tests and by the enzymatic clearance assay. Significantly lower lipid levels were found in patients with AD, than in controls. Patients in the late phase of AD had significantly lower entire lipid profile than controls and significantly lower cholesterol and LDL-C levels than patients in the middle stage ofAD. There was no difference in lipid levels between patients with and without psychotic features. The significant positive correlations were found between MMSE scores and cholesterol, LDL-C levels and age in all AD patients. The results support the presumption that lipid profile might be connected with the aetiology and progress of AD and showed the association between low serum cholesterol and LDL-C levels and cognitive decline in patients with AD. Further studies are needed to confirm the relationship between lipid levels and cognition, and to validate the lipid profile as a biological marker for the progress of AD.     

Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study

ObjectivesTo evaluate a simple three step procedure to identify people in the general population who are in the preclinical phase of Alzheimer''s disease and dementia.DesignThree year population based cohort study.SettingKungsholmen cohort, Stockholm, Sweden.Participants1435 people aged 75-95 years without dementia.AssessmentsSingle question asking about memory complaints, assessment by mini-mental state examination, and neuropsychological testing.ResultsNone of the three instruments was sufficiently predictive of Alzheimer''s disease and dementia when administered separately. After participants had been screened for memory complaints and global cognitive impairment, specific tests of word recall and verbal fluency had positive predictive values for dementia of 85-100% (95% confidence intervals range from 62% to 100%). However, only 18% of future dementia cases were identified in the preclinical phase by this three step procedure. Memory complaints were the most sensitive indicator of Alzheimer''s disease and dementia in the whole population, but only half the future dementia cases reported memory problems three years before diagnosis.ConclusionThis three step procedure, which simulates what might occur in clinical practice, has a high positive predictive value for dementia, although only a small number of future cases can be identified.

What is already known on this topic

Alzheimer''s disease is characterised by a preclinical phase, during which cognitive deficits are seen before diagnosisElderly people with subjective memory complaints and objective global cognitive impairment have a high risk of developing Alzheimer''s disease and dementia

What this study adds

This three step procedure (self report of memory complaints, test of global cognitive functioning, and then domain specific cognitive tests) has a positive predictivity of 85-100% for Alzheimer''s disease and dementia at three yearsHowever, only 18% of people in the preclinical phase can be identified using this procedureAbout half of the people in the preclinical phase of Alzheimer''s disease and dementia do not report problems with their memory three years before diagnosis