NINCDS-ADRDA Criteria Research Articles

Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: A longitudinal MRI study

Capturing the dynamics of gray matter (GM) atrophy in relation to the conversion from mild cognitive impairment (MCI) to clinically probable Alzheimer's disease (AD) would be of considerable interest. In this prospective study we have used a novel longitudinal voxel-based method to map the progression of GM loss in MCI patients over time and compared converters to non-converters. Eighteen amnestic MCI patients were followed-up for a predefined fixed period of 18 months and conversion was judged according to NINCDS-ADRDA criteria for probable AD. Each patient underwent a high-resolution T1-weighted volume MRI scan both at entry in the study and 18 months later. We used an optimal VBM protocol to compare baseline imaging data of converters to those of non-converters. Moreover, to map GM loss from baseline to follow-up assessment, we used a modified voxel-based morphometry (VBM) procedure specially designed for longitudinal studies. At the end of the follow-up period, seven patients had converted to probable AD. Areas of lower baseline GM value in converters mainly included the hippocampus, parahippocampal cortex, and lingual and fusiform gyri. Regions of significant GM loss over the 18-month follow-up period common to both converters and non-converters included the temporal neocortex, parahippocampal cortex, orbitofrontal and inferior parietal areas, and the left thalamus. However, there was significantly greater GM loss in converters relative to non-converters in the hippocampal area, inferior and middle temporal gyrus, posterior cingulate, and precuneus. This accelerated atrophy may result from both neurofibrillary tangles accumulation and parallel pathological processes such as functional alteration in the posterior cingulate. The ability to longitudinally assess GM changes in MCI offers new perspectives to better understand the pathological processes underlying AD and to monitor the effects of treatment on brain structure.

Tc-99m HMPAO brain SPECT findings in mild and moderate Alzheimer's disease: Correlation with event related potentials

We investigated whether brain SPECT findings show any differences between patients with mild and moderate Alzheimer's disease (AD) and to compare results with event related potentials (ERPs). Twenty-two patients with mild to moderate AD diagnosed according to NINCDS-ADRDA criteria and 10 age-matched control subjects were included in this prospective study. All subjects underwent ERP recordings and Tc-99m HMPAO brain SPECT study. Cortical perfusion index (CPI) was calculated as the ratio of cortical activity to the cerebellum activity. CPI was found to be statistically lower in bilaterally posterolateral temporal cortex and precuneus in the moderate AD compared to the control group. There was no statistically significant difference between the mild AD and control groups for CPI in any cortical areas. The mean P300 latency was statistically prolonged in the mild and moderate AD compared to the control group. In addition, in moderate AD P300 latency was longer than in mild AD. While the mean P300 amplitude was statistically reduced in moderate AD compared to the control and mild AD, there was no statistically significant difference between the mild AD and control groups. There was a strong negative correlation between P300 latency and CPI in the right and left precuneus in the moderate AD group. The present study suggested that Tc-99m HMPAO SPECT study is the more appropriate technique for patients with moderate AD rather than mild AD. Our results indicated that alterations in ERPs, especially prolongation of P300 latency could be a finding that occurred earlier than the deterioration in cerebral blood flow. We thought that precuneus is closely related to cognitive function and may have an important role in the pathophysiology of AD.

Differences and Similarities between Two Frequently Used Assays for Amyloid β 42 in Cerebrospinal Fluid

Amyloid β 42 (Aβ 42) concentrations in cerebrospinal fluid (CSF) are used to identify Alzheimer disease (AD) (1), but reported concentrations differ among studies, as does diagnostic accuracy (2). These differences may relate to the patient and control groups studied (3), processing and storage methods (4), intra- and interassay variation of the assays, or to the reagent antibodies used. A recent metaanalysis (2) stressed the importance of standardizing assays for Aβ–42 in CSF. In most studies, CSF Aβ 42 was reported to be decreased, but in 2 studies, CSF Aβ 42 was not significantly changed in AD (2), and in 1 study(5) even increased in the early stages of disease. These dissimilarities might reflect the specificities of the antibodies incorporated in the assays. The first aim of our study was to compare Aβ 42 concentrations measured by 2 different assays in the same CSF samples. The first assay, widely used in Europe (6), uses 2 monoclonal antibodies (mAbs) and detects the full-length Aβ 42 peptide, Aβ (1–42) (7). The second assay [Aβ (N–42)], used mainly in the United States (8), detects both full-length Aβ 42 and Aβ peptides truncated at the NH2 terminus (9). The second aim of our study was to compare diagnostic accuracies of the assays for patients with AD compared with controls without dementia and patients with frontotemporal lobar degeneration (FTLD). Finally, we investigated the relationship between CSF Aβ (1–42) and Aβ (N–42) concentrations and albumin ratio, age, disease duration, and disease severity. Between October 2000 and December 2002, we recruited 39 AD patients, 24 FTLD patients, and 30 non-dementia controls at the Alzheimer Center of the VU University Medical Center (VUMC). All patients underwent a standardized investigative battery (3). A diagnosis of “probable” AD was made according to the NINCDS-ADRDA criteria (10); the …

Switching From Donepezil to Rivastigmine Is Well Tolerated

Background: Transitioning patients between cholinesterase inhibitors was thought to require a washout period to avoid cholinergic toxicity; however, evidence suggests that abrupt discontinuation of donepezil may lead to cognitive decline. We evaluated the safety and tolerability of an immediate switch from donepezil to rivastigmine.Method: This is an analysis of the safety and tolerability data from the first 28 days of an open-label, multicenter, prospective trial, conducted from August 2002 to August 2003, in which patients satisfying NINCDS-ADRDA criteria for probable Alzheimer's disease were administered rivastigmine 1.5 mg b.i.d. within 24 to 36 hours of donepezil discontinuation. Results are compared with adverse event rates from a retrospective analysis of a pivotal, placebo-controlled trial examining patients not previously treated with a cholinesterase inhibitor.Results: Fifty-eight of 61 patients completed the first 28 days, with no suspected drug-related discontinuations during this period. Incidence of overall gastrointestinal adverse events at day 7 was 8.2%, and at day 28 was 11.5%. The corresponding rate for rivastigmine-treated patients in the retrospective analysis of the pivotal trial for day 7 was 3.3%.Conclusion: These study results suggest that transitioning patients from donepezil to rivastigmine without a washout period is safe and well tolerated.

Attention and Executive Control Predict Alzheimer Disease in Late Life: Results From the Berlin Aging Study (BASE)

Longitudinal studies of neuropsychological changes in the preclinical phase of Alzheimer disease (AD) have yielded mixed results. Although some studies report tests of episodic memory, others report tests of attention and executive functions as reliable predictors of subsequent AD. Following theoretical models of neuropsychological processes before AD onset, the authors examined the predictive value of attention and executive function in the preclinical phase of AD in old age. Authors studied the cognitive performance of 187 initially normal participants of the Berlin Aging Study, a community-based representative sample of Berlin citizens age 70 to 103, over a period of 4 years. Tests of attention and executive function (Digit Letter Test, Trailmaking Part B Test, Digit Symbol Substitution Test, and Identical Pictures Test) and of learning and recall functions (Activity Recall, Memory for Text, and Paired-Associate Learning) were administered at baseline. Diagnosis of AD was made according to NINCDS-ADRDA criteria (probable AD). Receiver operating characteristics curve analyses and Cox regression analyses were used to assess the diagnostic accuracy and predictive value of the neuropsychological tests at baseline for incident AD after 4 years. After 4 years, 15 participants had developed AD. Tests of attention and executive function discriminated best between nonconverters and incident AD cases. A similar pattern was found in survival analyses; attention and executive function tests, together with tests of learning and recall, significantly predicted incident AD over and above age, gender, and education. These results support theoretical models of attention and executive function in the preclinical phase of AD in old age.

Attention and Executive Control Predict Alzheimer Disease in Late Life: Results From the Berlin Aging Study (BASE)

<h3>Objective</h3> Longitudinal studies of neuropsychological changes in the preclinical phase of Alzheimer disease (AD) have yielded mixed results. Although some studies report tests of episodic memory, others report tests of attention and executive functions as reliable predictors of subsequent AD. Following theoretical models of neuropsychological processes before AD onset, the authors examined the predictive value of attention and executive function in the preclinical phase of AD in old age. <h3>Methods</h3> Authors studied the cognitive performance of 187 initially normal participants of the Berlin Aging Study, a community-based representative sample of Berlin citizens age 70 to 103, over a period of 4 years. Tests of attention and executive function (Digit Letter Test, Trailmaking Part B Test, Digit Symbol Substitution Test, and Identical Pictures Test) and of learning and recall functions (Activity Recall, Memory for Text, and Paired-Associate Learning) were administered at baseline. Diagnosis of AD was made according to NINCDS-ADRDA criteria (probable AD). Receiver operating characteristics curve analyses and Cox regression analyses were used to assess the diagnostic accuracy and predictive value of the neuropsychological tests at baseline for incident AD after 4 years. <h3>Results</h3> After 4 years, 15 participants had developed AD. Tests of attention and executive function discriminated best between nonconverters and incident AD cases. A similar pattern was found in survival analyses; attention and executive function tests, together with tests of learning and recall, significantly predicted incident AD over and above age, gender, and education. <h3>Conclusion</h3> These results support theoretical models of attention and executive function in the preclinical phase of AD in old age.

El Addenbrooke’s Cognitive Examination en español para el diagnóstico de demencia y para la diferenciación entre enfermedad de Alzheimer y demencia frontotemporal

The Addenbrooke's Cognitive Examination (ACE) is a brief bedside test battery to detect mild dementia and differentiate frontotemporal dementia (FTD) from Alzheimer's disease (AD). To validate the ACE in Spanish. The study evaluated the Spanish version of ACE on 128 subjects consisting in two groups a patient group (n = 76) and a control subjects group (n = 52). The patient group was divided in AD (n = 54) based on the NINCDS-ADRDA criteria and FTD (n = 22) based on the Lund y Manchester criteria. All patients underwent clinical, neuropsychological, radiologic (MRI, CT, and SPECT), and laboratory evaluations. Group's differences were evaluated using ANOVA. The internal consistency of the Spanish version of the ACE was measured using the Cronbach's alpha coefficient. The discriminative capability of the Spanish version of the ACE was examined by the receiver operating characteristic (ROC) analysis. The cut-off score of 86 showed a sensitivity of 92% (CI 95% = 83.6-97.0) and a specificity of 96.2% (CI 95% = 86.8-99.4). The ROC curve showed higher sensitivity and specificity of the ACE than the Mini-Mental State Examination in discriminating the dementia and control group. The VLOM ratio (verbal fluency + language)/(orientation + memory) of < 1.82 discriminated for FTD and > 4.87 discriminated for AD. The Spanish version of ACE is a brief and reliable instrument for early detection of dementia in highly educated people and offers a simple objective index to differentiate AD and FTD. More studies in less educated people are warranted.

Are serum lipid and lipoprotein levels related to dementia?

Although hyperlipidemia is known to contribute to vascular disease and it may play a role in dementia, specific studies for elderly are limited. The aim of this study is to examine the relationship between dyslipidemia and dementia. In this study, 1251 patients admitted to the Hacettepe University Division of Geriatric Medicine were enrolled. On the basis of the mini mental state examination (MMSE), the clock drawing test (CDT) scores, the APA DSM-IV and the NINCDS-ADRDA criteria and the Hachinski ischemic score (HIS), the subjects were divided into four groups: Alzheimer's disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and normal cognitive status (NCS). The lipoprotein levels were measured, and we analyzed the data using χ 2 and the one-way analysis of variance methods. Among the subjects, 14.8% had low high-density lipoproteins (HDL), 58.5% had high triglyceride (TG), 73.6% had high low-density lipoproteins (LDL), and 21.6% had high lipoprotein-a (Lp(a)) of our study population. There was no difference between the dementia subgroups and the NCS group in the lipoprotein levels. The only significant relationship was between high TG levels and the AD, as well as the MCI groups. Low HDL and high LDL are important problems in elderly. Although serum lipid levels, especially of Lp(a), has recently been thought to be related with dementia, our study suggests the absence of such a relationship. The national data regarding the elderly population should be evaluated on the basis of genetic and environmental factors in each country. The present study showing no significant relationship between Lp(a) and the cognitive status adds new information to the available literature.

18F]FDG-PET in Patients with Alzheimer’s Disease: Marker of Disease Spread

Background: It is not known yet whether temporoparietal glucose hypometabolism in patients with probable Alzheimer’s disease (AD) reflects disease severity or different subtypes of patients. Methods: Twenty-five subjects with mild probable AD [NINCDS-ADRDA criteria; age 65.8 ± 9.3 years (mean ± SD); Mini-Mental State Examination (MMSE) 26.0 ± 3.3] were investigated. [¹⁸F]FDG-PET data were analyzed visually with raters blinded to the diagnosis and with a quantitative analysis in the region of interest on individual anatomically normalized PET scans. Results: Thirteen of 25 patients showed temporoparietal hypometabolism on visual inspection (PET+; age 65.7 ± 10.7), 12 patients had normal FDG-PET results (PET–; age 65.9 ± 8.0; n.s.). The MMSE and immediate reproduction of the Wechsler Memory Scale (WMS-R-I) were 27.7 ± 1.9 and 31.1 ± 6.1 in the PET– vs. 24.5 ± 3.6 (p = 0.012) and 22.0 ± 7.4 (p = 0.006) in the PET+ group. Immediate and delayed recall in the California Verbal Learning Test and delayed reproduction in the Wechsler Memory Scale were alike. Regression analysis revealed a significant correlation of temporoparietal glucose metabolism with the block span (r = 0.60; p < 0.01) and the WMS-R-I (r = 0.68; p < 0.01) but not with measures of hippocampal function. Conclusions: Temporoparietal glucose metabolism in patients with very mild AD is a sign of disease spread beyond the temporal lobe. This may aid in establishing objective parameters for future therapeutic studies.

Motivational Symptoms of Depression Mask Preclinical Alzheimer’s Disease in Elderly Subjects

Background: Althoughthe relationship between depressive disorders and Alzheimer’s disease (AD) is debated, there is evidence that depression may be an early symptom of dementia. Objective: To evaluate depression features prospectively in elderly subjects with a view to identifying a subgroup affected by preclinical AD. Methods: We performed a cohort study on cognitive performances with a 12-month follow-up in out-patients referred to the local Neuropsychology Clinic complaining of memory problems. Two hundred and twenty-two consecutive non-demented subjects were studied using a neuropsychological battery and the Beck Depression Inventory (BDI) and assessed again 1 year later for the possible onset of cognitive impairment. Multivariate analysis was performed to detect independent predictors of dementia development among age, education, neuropsychological test scores and BDI scores and subscores. BDI subscores were obtained by dividing items into three domains corresponding to mood-related, somatic and motivation-related symptoms. Results: At the time of the first evaluation, 124 of the 222 subjects were depressed according to DSM-III-R criteria. At 1 year, 31 of the 124 depressed subjects and 2 non-depressed ones had AD according to NINCDS-ADRDA criteria. Stepwise logistic regression analysis indicated that the subjects who went on to develop dementia had significantly higher total BDI scores and motivational BDI subscores. Among depressed subjects, the probability of being diagnosed with dementia during follow-up was significantly associated with a motivational BDI subscore ≧7 (odds ratio: 3,885, 95% Cl 154–97,902). Comment: Close neuropsychological follow-up of depressed elderly subjects complaining of memory failure and showing apathy is recommended to detect the early stage of AD.

Effects of galantamine in patients with mild Alzheimer's disease

SUMMARYBackground: Galantamine is an acetylcholinesterase inhibitor that modulates nicotinic receptors. It is effective in mild to moderate Alzheimer’s disease (AD) but no trial has focused exclusively on mild AD. We performed a post-hoc sub-set analysis using data from four randomised trials to explore the efficacy of galantamine versus placebo in mild AD.Methods: Participants in all studies met NINCDS-ADRDA criteria for probable AD. We examined data from patients with baseline Mini Mental State Examination (MMSE) 21–24 who received galantamine 24 mg/day (GAL) or placebo (PLAC). Scores for the Alzheimer’s Disease Assessment Scale-cognitive subset (ADAS–cog), Clinician’s Interview–Based Impression of Change (CIBIC), Disability Assessment for Dementia (DAD), and ACDS-ADL scales were compared.Results:Of the 694 patients (362 GAL, 332 PLAC, mean baseline MMSE 22.4 ± 1.1, mean age 74 ± 7.9 years), 65% completed 6 months treatment (223 GAL, 229 PLAC). Mean change in ADAS-cog at 6 months was –1.5 (95% confidence interval –2.2, –0.8, p < 0.001) for GAL and + 0.2 (–0.6, 0.9, p = 0.72) for PLAC. This difference was statistically significant ( p = 0.001).Significantly more patients receiving galantamine were classified as ‘improved’ using the CIBIC (26.9% GAL vs 14.3% PLAC, p < 0.001). Galantamine was generally well tolerated; most common adverse events were nausea, vomiting and diarrhoea.Conclusion: Pooled data from four randomised trials of patients with mild AD indicate that patients who received galantamine 24 mg/day for 6 months improved cognition more often than those who received placebo and that a higher proportion receiving galantamine were globally improved. This suggests that patients with mild AD benefit from galantamine treatment.

White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease

Background and objective: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method...

Distribution of cerebral atrophy assessed by magnetic resonance imaging reflects patterns of neuropsychological deficits in Alzheimer's dementia*1

Neuropsychological deficits were investigated with respect to regional distribution of cerebral atrophy as assessed by volumetric magnetic resonance imaging (MRI) in 50 patients with Alzheimer's dementia (AD; NINCDS-ADRDA criteria) and 20 healthy volunteers. When compared between groups, test performance of all investigated neuropsychological domains including declarative memory, language, praxia, psychomotor speed, as well as attention and concentration was significantly impaired. These deficits were differentially correlated with regional atrophic changes. In particular, volumes of the right amygdala–hippocampus complex correlated with declarative memory performance, whereas volumes of the left temporo-parietal regions correlated with performance in naming and praxia. Furthermore, left frontal lobe atrophy was associated with verbal fluency. Our data confirm the central role that medial temporal atrophy plays for declarative memory deficits in AD and indicate that additional changes in the parietal, temporal and frontal lobes are responsible for further neuropsychological deficits characteristic of this disorder.

Shortening of hippocampal spin-spin relaxation time in probable Alzheimer's disease: a 1H magnetic resonance spectroscopy study

We quantified the differential effects of the spin-spin relaxation times (T 2) of tissue water and cerebral spinal fluid in order to examine hippocampal T 2 changes as a non-invasive bio-marker of Alzheimer's disease (AD). We measured T 2 in the right hippocampus of ten patients fulfilling the NINCDS-ADRDA criteria for AD and 40 healthy adult volunteers using localized proton magnetic resonance spectroscopy. The T 2 values of AD patients (73±8 ms) were significantly shorter ( P<0.01) than those of healthy age-matched controls (81±5 ms), and there was a reduction in T 2 for healthy older vs. healthy younger adults (87±5 ms, P<0.05). The reduced T 2 values with aging are consistent with age-related decreases in tissue water content. Our results suggest that there may be a severe reduction in tissue water content in AD.

Neuropsychological correlates of cerebral atrophy in Alzheimer's dementia

This study aims to systematically analyze the relationship between neuropsychological deficits and regional cerebral atrophic changes in Alzheimer's dementia (AD). As an extension of previous studies we not only investigated substructures of the medial temporal lobe but also included other relevant cerebral regions such as frontal, temporal, and parietal lobes. This approach was based on the assumption that morphological correlates of global and specific cognitive dysfunction might reflect to a certain degree the neuronal basis of the respective function. Accordingly, the functional role assigned to a certain cerebral structure or region can be further elucidated which might lead to a better understanding of the clinical and neuropsychological heterogeneity of AD. Fifty patients with AD (NINCDS-ADRDA criteria) and 20 healthy elderly control subjects were included. All patients and controls were examined on a standardized neuropsychological test battery. In addition, magnetic resonance imaging (MRI) of the brain was performed. Volumes of the whole brain, CSF-spaces, amygdala-hippocampus complex, frontal lobes, temporal lobes, and parietal lobes were measured using a standardized protocol. AD-patients were characterized by neuropsychological deficits with respect to memory, language, praxia, cognitive speed as well as attention and concentration. These deficits were differentially correlated with regional atrophic changes. In particular, volumes of the right amygdala-hippocampus complex were correlated with declarative memory performance in the non-verbal visual domain. Furthermore, an association between left temporo-parietal regions and aspects of semantic memory, as well as verbal recall and left frontal regions could be established. The validity of our results is supported by recent findings from neuropathological and functional neuroimaging studies. In conclusion, our data indicate that MRI-based volumetry can be successfully used to detect morphological correlates of neuropsychological heterogeneity in AD and that this methodological approach allows to fruitfully study the neuronal basis of cognitive functions.

Identification of families with cortical Lewy body disease.

Until recently, cortical Lewy body disease (CLB) was considered essentially the same as dementia with Lewy bodies (DLB). It is now known patients with Parkinson's disease (PD) with a later-onset dementia (PD-dementia) have the same pattern and extent of cortical Lewy body pathology. Inheritance patterns of CLB have not been evaluated previously. To identify genetic influence on CLB, all cases with this pathology need to be considered. We selected 180 cases meeting clinical and/or pathological criteria for DLB or PD (+/-dementia) from two patient groups: a PD and PD-dementia brain donor program, and a case-control study of Alzheimer's disease (AD). Cases meeting NINCDS-ADRDA criteria for probable AD were excluded and non-demented PD cases used as a comparison group. A detailed family history was taken analyzing onset and progression of dementia and PD phenotypes and a family tree constructed. The frequency of a positive family history of dementia and/or PD and risk of developing CLB in relatives was calculated. Fifty-five percent of dementia and 52% of PD cohorts did not have relatives with clinical disease. There was no increased frequency of familial disease in the CLB cohort compared with PD. However, in half the CLB families, rather than a dominant dementia, the clinical presentation varied (dementia and/or PD). Unlike PD, there was an increased risk of dementia if CLB was present in a parent ( approximately 20% risk) compared with another family member ( approximately 5% risk), suggesting CLB is more likely than PD to occur in a pattern consistent with autosomal dominant inheritance.

Distribution of cerebral atrophy assessed by magnetic resonance imaging reflects patterns of neuropsychological deficits in Alzheimer's dementia

Neuropsychological deficits were investigated with respect to regional distribution of cerebral atrophy as assessed by volumetric magnetic resonance imaging (MRI) in 50 patients with Alzheimer's dementia (AD; NINCDS-ADRDA criteria) and 20 healthy volunteers. When compared between groups, test performance of all investigated neuropsychological domains including declarative memory, language, praxia, psychomotor speed, as well as attention and concentration was significantly impaired. These deficits were differentially correlated with regional atrophic changes. In particular, volumes of the right amygdala–hippocampus complex correlated with declarative memory performance, whereas volumes of the left temporo-parietal regions correlated with performance in naming and praxia. Furthermore, left frontal lobe atrophy was associated with verbal fluency. Our data confirm the central role that medial temporal atrophy plays for declarative memory deficits in AD and indicate that additional changes in the parietal, temporal and frontal lobes are responsible for further neuropsychological deficits characteristic of this disorder.

Dementia severity and Lewy bodies affect circadian rhythms in Alzheimer disease

Sleep disturbance is a symptom shared by all neurodegenerative, dementing illnesses, such as Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), and its presence frequently precipitates decisions to seek institutional care for patients. Although the sleep disturbances of AD and DLB are qualitatively similar, they appear to be more prominent in patients with DLB. Disturbance of the circadian rhythm has been noted and is a potential factor underlying the nocturnal sleep fragmentation and daytime sleepiness observed in these patients. We studied the circadian variation of core-body temperature and motor activity in a total of 32 institutionalized patients with probable AD by NINCDS-ADRDA criteria, 9 of whom also met pathologic criteria for DLB. Eight, healthy, elderly male controls were studied on a clinical research unit designed to simulate the hospital environment where the dementia patients were studied. Circadian variables generally had greater deviations from normal associated with increasing AD pathology, as measured by postmortem-determined Braak stage, supporting the hypothesis that central changes mediate circadian disturbances in AD and DLB. Patients with a postmortem diagnosis of DLB manifested greater disturbances of locomotor activity circadian rhythms than patients with AD, possibly reflecting the greater sleep disturbances seen in this population, but the differences from normal in the circadian rhythms of the AD and DLB patients were qualitatively similar.

EEG synchronization likelihood in mild cognitive impairment and Alzheimer's disease during a working memory task

Objective Synchronization likelihood analysis of resting state EEG has shown that cognitive dysfunction in Alzheimer's disease (AD) and its precursor mild cognitive impairment (MCI) are associated with a loss of functional connectivity in high (upper α and β) frequency bands. Working memory tasks are known to change functional connectivity, but it is unknown whether this increases the differences between AD, MCI and healthy controls. Our objective was to investigate the behavior of synchronization likelihood of multichannel EEG in AD, MCI and cognitively healthy controls, both at rest and during a working memory task. Methods EEGs (200 Hz sample frequency, 21 channels, average reference) were recorded at rest as well as during a visual working memory task in 14 patients with AD according to the NINCDS-ADRDA criteria (mean age 76.4; SD 13.6), 11 patients with MCI according to the criteria of Petersen (mean age 78.4; SD 6.4) and 14 with subjective memory complaints but no demonstrable memory disturbance (mean age 61.6; SD 26.6). The synchronization likelihood was computed over 19 channels, comparing each channel with all the other channels for the 0.5–4, 4–8, 8–10, 10–12, 12–30, 30–50 Hz frequency bands. Results The synchronization likelihood was significantly decreased in the upper α (10–12) and β (12–30) bands in AD compared to persons with subjective memory complaints. The working memory task scores strongly correlated with Mini-Mental State Examination scores. During the working memory task the synchronization likelihood was significantly higher in MCI compared to the control subjects in the lower α band (8–10 Hz). Conclusions Decrease of β band synchronization occurs in mild AD, both in a resting condition and during a working memory task. Significance Decrease of β band synchronization in mild AD is a robust finding. The present study confirms our findings in a different cohort of patients, using alternative frequency bands. The diagnostic value of the synchronization likelihood in AD and MCI needs to be further established.

HOMOCYSTEINE IN ALZHEIMER DISEASE AND VASCULAR DEMENTIA

Hyperhomocysteinemia is an important risk factor for atherosclerosis and it has recently been suggested as a diagnostic marker for Alzheimer disease (AD). The present studies compared homocysteinemia in patients with AD and with vascular dementia (VD),as well as in controls. Homocysteinemia was measured in 137 probable AD patients,diagnosed by the NINCDS-ADRDA criteria, in 40 probably VD patients diagnosed by the NINDS-AIREN criteria, and in 42 control subjects. Homocysteine levels were significantly higher in AD and VD groups, than in controls, however, VD patients were significantly older than the controls. The proportion of females was higher in the AD group, while serum folate and B12 vitamin levels tended to be lower in both the AD and VD groups, compared to the controls. In order to adjust the results for these potentially interfering factors, a multivariate ANCOVA calculation was performed, where homocysteine levels were analyzed considering 2 grouping factors (gender and neurological type) and 4 covariates (age, albumin,serum folate and vitamin B12 ). This analysis confirmed that even after adjusting for the covariates, the difference between AD and VD groups and controls remain highly significant,while neither the gender itself, nor the interaction of gender and the neurological type had any significant influence on the homocysteine levels. The main finding, therefore, is a significant increase of homocysteine levels in the 2 disease groups, compared to controls.