Subclinical epileptiform discharges in Alzheimer's disease are associated with increased hippocampal blood flow.

BACKGROUND: In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer's disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus. METHODS: A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG. RESULTS: No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value < 0.001). Changes in areas that typically show group differences (temporal-parietal cortex) were found in patients with AD, compared to HC. CONCLUSIONS: Increased spike frequency was accompanied by a hemodynamic response of increased blood flow in the hippocampus in patients with AD. This phenomenon has also been shown in patients with epilepsy and supports the hypothesis of hyperexcitability in patients with AD. The lack of a significant difference in hippocampal rCBF may be due to an increased frequency of epileptiform discharges in patients with AD. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov (NCT04436341).

Subclinical Epileptiform Activity in Dementia with Lewy Bodies.

BACKGROUND: Patients with dementia with Lewy bodies (DLB) have a higher probability of seizures than in normal aging and in other types of neurodegenerative disorders. Depositions of α-synuclein, a pathological hallmark of DLB, can induce network excitability, which can escalate into seizure activity. Indicator of seizures are epileptiform discharges as observed using electroencephalography (EEG). However, no studies have so far investigated the occurrence of interictal epileptiform discharges (IED) in patients with DLB. OBJECTIVES: To investigate if IED as measured with ear-EEG occurs with a higher frequency in patients with DLB compared to healthy controls (HC). METHODS: In this longitudinal observational exploratory study, 10 patients with DLB and 15 HC were included in the analysis. Patients with DLB underwent up to three ear-EEG recordings, each lasting up to 2 days, over a period of 6 months. RESULTS: At baseline, IED were detected in 80% of patients with DLB and in 46.7% of HC. The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with DLB as compared to HC with a risk ratio of 2.52 (CI, 1.42-4.61; P-value = 0.001). Most IED occurred at night. CONCLUSIONS: Long-term outpatient ear-EEG monitoring detects IED in most patients with DLB with an increased spike frequency compared to HC. This study extends the spectrum of neurodegenerative disorders in which epileptiform discharges occurs at an elevated frequency. It is possible that epileptiform discharges are, therefore, a consequence of neurodegeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Detection of subclinical epileptiform discharges in Alzheimer's disease using long-term outpatient EEG monitoring.

BACKGROUND: In patients with Alzheimer's disease (AD) without clinical seizures, up to half have epileptiform discharges on long-term in-patient electroencephalography (EEG) recordings. Long-term in-patient monitoring is obtrusive, and expensive as compared to outpatient monitoring. No studies have so far investigated if long-term outpatient EEG monitoring is able to identify epileptiform discharges in AD. Our aim is to investigate if epileptiform discharges as measured with ear-EEG are more common in patients with AD compared to healthy elderly controls (HC). METHODS: In this longitudinal observational study, 24 patients with mild to moderate AD and 15 age-matched HC were included in the analysis. Patients with AD underwent up to three ear-EEG recordings, each lasting up to two days, within 6 months. RESULTS: The first recording was defined as the baseline recording. At baseline, epileptiform discharges were detected in 75.0% of patients with AD and in 46.7% of HC (p-value = 0.073). The spike frequency (spikes or sharp waves/24 h) was significantly higher in patients with AD as compared to HC with a risk ratio of 2.90 (CI: 1.77-5.01, p < 0.001). Most patients with AD (91.7%) showed epileptiform discharges when combining all ear-EEG recordings. CONCLUSIONS: Long-term ear-EEG monitoring detects epileptiform discharges in most patients with AD with a three-fold increased spike frequency compared to HC, which most likely originates from the temporal lobes. Since most patients showed epileptiform discharges with multiple recordings, elevated spike frequency should be considered a marker of hyperexcitability in AD.

Aerobic exercise does not affect serum neurofilament light in patients with mild Alzheimer's disease.

Introduction: Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration. Objective: To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer's disease (AD). Methods: This is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer's disease: The Effect of Physical Exercise (ADEX) study. Participants were randomized to 16 weeks of moderate intensity aerobic exercise or usual care. Clinical assessment and measurement of serum NfL was done at baseline and after the intervention. Results: A total of 136 participants were included in the analysis. Groups were comparable at baseline except for APOEε4 carriership which was higher in the usual care group (75.3 versus 60.2%; p = 0.04). There was no effect of the intervention on serum NfL [intervention: baseline NfL (pg/mL) 25.76, change from baseline 0.87; usual care: baseline 27.09, change from baseline -1.16, p = 0.09]. Conclusion: The findings do not support an effect of the exercise intervention on a single measure of neurodegeneration in AD. Further studies are needed using other types and durations of exercise and other measures of neurodegeneration. Clinical trial registration: clinicaltrials.gov, identifier NCT01681602.

Long-Term EEG Monitoring in Patients with Alzheimer's Disease Using Ear-EEG: A Feasibility Study.

BACKGROUND: Previous studies have reported that epileptiform activity may be detectible in nearly half of patients with Alzheimer's disease (AD) on long-term electroencephalographic (EEG) recordings. However, such recordings can be uncomfortable, expensive, and difficult. Ear-EEG has shown promising results for long-term EEG monitoring, but it has not been used in patients with AD. OBJECTIVE: To investigate if ear-EEG is a feasible method for long-term EEG monitoring in patients with AD. METHODS: In this longitudinal, single-group feasibility study, ten patients with mild to moderate AD were recruited. A total of three ear-EEG recordings of up to 48 hours three months apart for six months were planned. RESULTS: All patients managed to wear the ear-EEG for at least 24 hours and at least one full night. A total of 19 ear-EEG recordings were performed (self-reported recording, mean: 37.15 hours (SD: 8.96 hours)). After automatic pre-processing, a mean of 27.37 hours (SD: 7.19 hours) of data with acceptable quality in at least one electrode in each ear was found. Seven out of ten participants experienced mild adverse events. Six of the patients did not complete the study with three patients not wanting to wear the ear-EEG anymore due to adverse events. CONCLUSION: It is feasible and safe to use ear-EEG for long-term EEG monitoring in patients with AD. Minor adjustments to the equipment may improve the comfort for the participants.

Comparison of the clinical impact of 2-[18F]FDG-PET and cerebrospinal fluid biomarkers in patients suspected of Alzheimer's disease.

BACKGROUND: The two biomarkers 2-[18F]FDG-PET and cerebrospinal fluid biomarkers are both recommended to support the diagnosis of Alzheimer's disease. However, there is a lack of knowledge for the comparison of the two biomarkers in a routine clinical setting. OBJECTIVE: The aim was to compare the clinical impact of 2-[18F]FDG-PET and cerebrospinal fluid biomarkers on diagnosis, prognosis, and patient management in patients suspected of Alzheimer's disease. METHODS: Eighty-one patients clinically suspected of Alzheimer's disease were retrospectively included from the Copenhagen Memory Clinic. As part of the clinical work-up all patients had a standard diagnostic program examination including MRI and ancillary investigations with 2-[18F]FDG-PET and cerebrospinal fluid biomarkers. An incremental study design was used to evaluate the clinical impact of the biomarkers. First, the diagnostic evaluation was based on the standard diagnostic program, then the diagnostic evaluation was revised after addition of either cerebrospinal fluid biomarkers or 2-[18F]FDG-PET. At each diagnostic evaluation, two blinded dementia specialists made a consensus decision on diagnosis, prediction of disease course, and change in patient management. Confidence in the decision was measured on a visual analogue scale (0-100). After 6 months, the diagnostic evaluation was performed with addition of the other biomarker. A clinical follow-up after 12 months was used as reference for diagnosis and disease course. RESULTS: The two biomarkers had a similar clinical value across all diagnosis when added individually to the standard diagnostic program. However, for the correctly diagnosed patient with Alzheimer's disease cerebrospinal fluid biomarkers had a significantly higher impact on diagnostic confidence (mean scores±SD: 88±11 vs. 82±11, p = 0.046) and a significant reduction in the need for ancillary investigations (23 vs. 18 patients, p = 0.049) compared to 2-[18F]FDG-PET. CONCLUSION: The two biomarkers had similar clinical impact on diagnosis, but cerebrospinal fluid biomarkers had a more significant value in corroborating the diagnosis of Alzheimer's disease compared to 2-[18F]FDG-PET.

Biomarker counseling, disclosure of diagnosis and follow-up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey.

OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. METHODS: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. RESULTS: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. CONCLUSIONS: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning.

Physical Exercise May Increase Plasma Concentration of High-Density Lipoprotein-Cholesterol in Patients With Alzheimer's Disease.

Lifestyle factors have been shown to increase the risk of developing Alzheimer's disease (AD) later in life. Specifically, an unfavorable cholesterol profile, and insulin resistance are associated with increased risk of developing AD. One way to non-pharmacologically affect the levels of plasma lipids is by exercise, which has been shown to be beneficial in cognitively healthy individuals. In this randomized controlled trial y, we therefore aimed to clarify the effect of physical exercise on the lipid profile, insulin and glucose in patients with AD. In addition, we investigated the effect of apolipoproteinE genotype on total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) in plasma from patients with AD. Plasma samples from 172 patients who underwent 16 weeks of moderate-to-high intensity exercise (n = 90) or treatment as usual (n = 82) were analyzed change from baseline for the levels of total cholesterol, LDL-C, HDL-C, TG, glucose, and insulin. In addition, we analyzed those from the exercise group who adhered to the protocol with an attendance of 2/3 or more of the exercise session and who followed the protocol of an intensity of 70% of the maximum heart rate. We found a significant increase in plasma HDL-C levels between the "high exercise sub-group" compared to control group. After intervention HDL-C was increased by 4.3% in the high-exercise group, and decreased by 0.7% in the control group, after adjustment for statin use. In conclusion, short term physical activity may be beneficial on the cholesterol profile in patients with AD.

Cholinergic dysfunction, neurodegeneration, and amyloid-beta pathology in neurodegenerative diseases.

Cholinergic dysfunction is central in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The electroencephalography-based acetylcholine index (EEG-Ach index) has been proposed as a biomarker of cholinergic dysfunction. However, it is unclear how the EEG-Ach index relates to amyloid-beta pathology and neurodegeneration. We investigated the association between the EEG-Ach index and cerebrospinal fluid (CSF) amyloid-beta, CSF total tau, cortical thickness, and hippocampal volume from magnetic resonance imaging (MRI), and cognition. A total of 127 patients with different neurodegenerative diseases were studied. The EEG-Ach index was calculated from quantitative EEG using statistical pattern recognition. The EEG-Ach index was associated with hippocampal volume and cortical thickness in frontal, temporal, and occipital cortices. Cross-sectional sub-analyses based on a small sample suggests that the EEG-Ach index increases the closest to AD dementia, downstream to amyloid-beta pathology, CSF total tau, and hippocampal volume. We conclude that cholinergic dysfunction correlates with atrophy in brain areas important for AD pathogenesis, and this association is more prominent in the dementia stage. These results together with previous studies from this project suggest that the EEG-Ach index may be a useful biomarker for cholinergic dysfunction, with value for differential diagnosis of dementia and monitoring patients at the dementia stage.

A visual rating scale for cingulate island sign on 18F-FDG-PET to differentiate dementia with Lewy bodies and Alzheimer's disease.

Valid diagnosis of dementia with Lewy bodies (DLB) is essential to establish appropriate treatment and care. However, the diagnostic accuracy is complicated by clinical and pathological overlap with Alzheimer's disease (AD). Cingulate island sign (CIS), defined as sparing of posterior cingulate cortex (PCC) relative to precuneus and cuneus on 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET), is included in the revised diagnostic DLB criteria. There are no guidelines for the visual grading of CIS, although visual rating is a fast-applicable method in a clinical setting. The objective was to develop a robust visual CIS scale and evaluate the performance in differentiating DLB with and without amyloid beta pathology (Aß+/-), and AD. 18F-FDG-PET scans from 35 DLB patients, 36 AD patients, and 23 healthy controls were rated according to a visual CIS scale based on specific reading criteria. The visual CIS scale was validated against a quantitative CIS ratio derived from a region of interest analysis of PCC, precuneus, and cuneus. DLB patients had a significantly higher visual CIS score compared to AD patients, and controls. A cut-off visual CIS score of 4 significantly differentiated DLB Aß- patients from DLB Aß+ patients. In conclusion, the visual CIS scale is clinically useful to differentiate DLB from AD. The degree of CIS may be related to Aß pathology in DLB patients.

Oscillatory connectivity as a diagnostic marker of dementia due to Alzheimer's disease.

OBJECTIVE: Quantitative EEG power has not been as effective in discriminating between healthy aging and Alzheimer's disease as conventional biomarkers. But EEG coherence has shown promising results in small samples. The overall aim was to evaluate if EEG connectivity markers can discriminate between Alzheimer's disease, mild cognitive impairment, and healthy aging and to explore the early underlying changes in coherence. METHODS: EEGs were included in the analysis from 135 healthy controls, 117 patients with mild cognitive impairment, and 117 patients with Alzheimer's disease from six Nordic memory clinics. Principal component analysis was performed before multinomial regression. RESULTS: We found classification accuracies of above 95% based on coherence, imaginary part of coherence, and the weighted phase-lag index. The most prominent changes in coherence were decreased alpha coherence in Alzheimer's disease, which was correlated to the scores of the 10-word test in the Consortium to Establish a Registry for Alzheimer's Disease battery. CONCLUSIONS: The diagnostic accuracies for EEG connectivity measures are higher than findings from studies investigating EEG power and conventional Alzheimer's disease biomarkers. Furthermore, decreased alpha coherence is one of the earliest changes in Alzheimer's disease and associated with memory function. SIGNIFICANCE: EEG connectivity measures may be useful supplementary diagnostic classifiers.

Impact of a Clinical Decision Support Tool on Dementia Diagnostics in Memory Clinics: The PredictND Validation Study.

BACKGROUND: Determining the underlying etiology of dementia can be challenging. Computer- based Clinical Decision Support Systems (CDSS) have the potential to provide an objective comparison of data and assist clinicians. OBJECTIVES: To assess the diagnostic impact of a CDSS, the PredictND tool, for differential diagnosis of dementia in memory clinics. METHODS: In this prospective multicenter study, we recruited 779 patients with either subjective cognitive decline (n=252), mild cognitive impairment (n=219) or any type of dementia (n=274) and followed them for minimum 12 months. Based on all available patient baseline data (demographics, neuropsychological tests, cerebrospinal fluid biomarkers, and MRI visual and computed ratings), the PredictND tool provides a comprehensive overview and analysis of the data with a likelihood index for five diagnostic groups; Alzheimer´s disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and subjective cognitive decline. At baseline, a clinician defined an etiological diagnosis and confidence in the diagnosis, first without and subsequently with the PredictND tool. The follow-up diagnosis was used as the reference diagnosis. RESULTS: In total, 747 patients completed the follow-up visits (53% female, 69±10 years). The etiological diagnosis changed in 13% of all cases when using the PredictND tool, but the diagnostic accuracy did not change significantly. Confidence in the diagnosis, measured by a visual analogue scale (VAS, 0-100%) increased (ΔVAS=3.0%, p<0.0001), especially in correctly changed diagnoses (ΔVAS=7.2%, p=0.0011). CONCLUSION: Adding the PredictND tool to the diagnostic evaluation affected the diagnosis and increased clinicians' confidence in the diagnosis indicating that CDSSs could aid clinicians in the differential diagnosis of dementia.

A 16-Week Aerobic Exercise Intervention Does Not Affect Hippocampal Volume and Cortical Thickness in Mild to Moderate Alzheimer's Disease.

Introduction: Brain imaging studies in healthy elderly subjects suggest a positive effect of aerobic exercise on both brain structure and function, while the effects of aerobic exercise in Alzheimer's Disease (AD) has been scarcely investigated. Methods: In a single-blinded randomized MRI study, we assessed the effects of an aerobic exercise intervention on brain volume as measured by magnetic resonance imaging (MRI) and its correlation to cognitive functioning in patients with AD. The study was a sub-study of a larger randomized controlled trial (ADEX study). Forty-one patients were assigned to a control or exercise group. The exercise group performed 60-min of aerobic exercise three times per week for 16 weeks. All participants underwent whole-brain MRI at 3 Tesla and cognitive assessment at baseline and after 16 weeks. Attendance and intensity were monitored providing a total exercise load. Changes in regional brain volumes and cortical thickness were analyzed using Freesurfer software. Results: There was no effect of the type of intervention on MRI-derived brain volumes. In the entire group with and without training, Exercise load showed a positive correlation with changes in volume in the hippocampus, as well as frontal cortical thickness. Volume changes in frontal cortical thickness correlated with changes in measures of mental speed and attention and exercise load in the exercise group. Conclusion: We did not find evidence to support an effect of 16 weeks of aerobic exercise on brain volume changes in patients with AD. Longer intervention periods may be needed to affect brain structure as measured with volumetric MRI. Clinical Trial registration: ClinicalTrials.gov Identifier: NCT01681602, registered September 10th, 2012 (Retrospectively registered).

EEG Theta Power Is an Early Marker of Cognitive Decline in Dementia due to Alzheimer's Disease.

BACKGROUND: Quantitative EEG (qEEG) power could potentially be used as a diagnostic tool for Alzheimer's disease (AD) and may further our understanding of the pathophysiology. However, the early qEEG power changes of AD are not well understood. OBJECTIVE: To investigate the early changes in qEEG power and the possible correlation with memory function and cerebrospinal fluid biomarkers. In addition, whether qEEG power could discriminate between AD, mild cognitive impairment (MCI), and older healthy controls (HC) at the individual level. METHODS: Standard EEGs from 138 HC, 117 MCI, and 117 AD patients were included from six Nordic memory clinics. All EEGs were recorded consecutively before the diagnosis and were not used for the consensus diagnosis. Absolute and relative power was calculated for both eyes closed and open condition. RESULTS: At group level using relative power, we found significant increases globally in the theta band and decreases in high frequency power in the temporal regions for eyes closed for AD and, to a lesser extent, for MCI compared to HC. Relative theta power was significantly correlated with multiple neuropsychological measures and had the largest correlation coefficient with total tau. At the individual level, the classification rate for AD and HC was 72.9% for relative power with eyes closed. CONCLUSION: Our findings suggest that the increase in relative theta power may be the first change in patients with dementia due to AD. At the individual level, we found a moderate classification rate for AD and HC when using EEGs alone.

Quantitative Electroencephalography Analyzed by Statistical Pattern Recognition as a Diagnostic and Prognostic Tool in Mild Cognitive Impairment: Results from a Nordic Multicenter Cohort Study.

AIM: To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) analyzed by the statistical pattern recognition (SPR) method in patients with cognitive impairment. We compared the differential diagnostic ability of SPR to visual EEG analysis. Correlation between SPR findings and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers were evaluated. METHODS: It is a multicenter cohort study involving 129 patients, (mild cognitive impairment [MCI], AD, and healthy controls). Standardized EEG was performed at baseline. Patients were continuously clinically evaluated. RESULTS: Receiver Operating Characteristic curves showed a low discriminative ability of SPR and no ability to predict clinical progression in patients with MCI. Moderate correlation between SPR analysis and CSF AD biomarkers was found. CONCLUSION: The diagnostic and prognostic abilities of qEEG were low. The SPR method was superior to the visual EEG analysis. The qEEG method correlates well to CSF AD biomarkers, suggesting association with pathology in AD.

Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers.

BACKGROUND/AIMS: Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We tested the diagnostic value of qEEG-SPR in comparison to cognition, structural imaging, and cerebrospinal fluid (CSF) biomarkers. METHODS: A total of 511 individuals were recruited from the multicenter NORD EEG study [141 healthy controls, 64 subjective cognitive decline, 124 mild cognitive impairment, 135 Alzheimer's disease (AD), 15 dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex. RESULTS: qEEG-SPR outperformed structural imaging, cognition, and CSF biomarkers in DLB/PDD diagnosis, outperformed structural imaging in AD diagnosis, and improved the differential diagnosis of AD. In addition, qEEG-SPR allowed differentiation of two clinically different AD subtypes. CONCLUSION: Adding qEEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers.

Effect of aerobic exercise on physical performance in patients with Alzheimer's disease.

INTRODUCTION: Knowledge about the feasibility and effects of exercise programs to persons with Alzheimer's disease is lacking. This study investigated the effect of aerobic exercise on physical performance in community-dwelling persons with mild Alzheimer's disease. METHODS: The single blinded multi-center RCT (ADEX) included 200 patients, median age 71 yrs (50-89). The intervention group received supervised moderate-to-high intensity aerobic exercise 1 hour × 3/week for 16 weeks. Assessments included cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy. RESULTS: Significant between-group differences in change from baseline (mean [95%CI]) favored the intervention group for cardiorespiratory fitness (4.0 [2.3-5.8] ml/kg/min, P <0.0001) and exercise self-efficacy (1.7 [0.5-2.8] points, P =0.004). Furthermore, an exercise attendance of ≥66.6% resulted in significant positive effects on single-task physical performance and dual-task performance. DISCUSSION: Aerobic exercise has the potential to improve cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy in community-dwelling patients with mild Alzheimer's disease.

Differences in quantitative methods for measuring subjective cognitive decline - results from a prospective memory clinic study.

BACKGROUND: Cognitive complaints occur frequently in elderly people and may be a risk factor for dementia and cognitive decline. Results from studies on subjective cognitive decline are difficult to compare due to variability in assessment methods, and little is known about how different methods influence reports of cognitive decline. METHODS: The Subjective Memory Complaints Scale (SMC) and The Memory Complaint Questionnaire (MAC-Q) were applied in 121 mixed memory clinic patients with mild cognitive symptoms (mean MMSE = 26.8, SD 2.7). The scales were applied independently and raters were blinded to results from the other scale. Scales were not used for diagnostic classification. Cognitive performances and depressive symptoms were also rated. We studied the association between the two measures and investigated the scales' relation to depressive symptoms, age, and cognitive status. RESULTS: SMC and MAC-Q were significantly associated (r = 0.44, N = 121, p = 0.015) and both scales had a wide range of scores. In this mixed cohort of patients, younger age was associated with higher SMC scores. There were no significant correlations between cognitive test performances and scales measuring subjective decline. Depression scores were significantly correlated to both scales measuring subjective decline. Linear regression models showed that age did not have a significant contribution to the variance in subjective memory beyond that of depressive symptoms. CONCLUSIONS: Measures for subjective cognitive decline are not interchangeable when used in memory clinics and the application of different scales in previous studies is an important factor as to why studies show variability in the association between subjective cognitive decline and background data and/or clinical results. Careful consideration should be taken as to which questions are relevant and have validity when operationalizing subjective cognitive decline.

Autonomic Dysfunction in Patients with Mild to Moderate Alzheimer's Disease.

BACKGROUND: Autonomic function has received little attention in Alzheimer's disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function. OBJECTIVE: To investigate autonomic function using standardized techniques in patients with AD and healthy age-matched controls. METHOD: Thirty-three patients with mild to moderate AD and 30 age- and gender-matched healthy controls, without symptoms of autonomic dysfunction, underwent standardized autonomic testing with deep breathing, Valsalva maneuver, head-up tilt, and isometric handgrip test. Brachial pressure curve and electrocardiogram were recorded for off-line analysis of blood pressure and beat-to-beat heart rate (HR). RESULTS: AD patients had impaired blood pressure responses to Vasalva maneuver (p < 0.0001) and HR response to isometric contraction (p = 0.0001). A modified composite autonomic scoring scale showed greater degree of autonomic impairment in patients compared to controls (patient: 2.1 ±â€Š1.6; controls: 0.9 ±â€Š1.1, p = 0.001). HR response to deep breathing and Valsalva ratio were similar in the two groups. CONCLUSION: We identified autonomic impairment ranging from mild to severe in patients with mild to moderate AD, who did not report autonomic symptoms. Autonomic impairment was mainly related to impairment of sympathetic function and evident by impaired blood pressure response to the Vasalva maneuver. The clinical implications of this finding are that AD may be associated with autonomic disturbances, but patients with AD may rarely report symptoms of autonomic dysfunction. Future research should systematically evaluate symptoms of autonomic function and characterize risk factors associated with autonomic dysfunction.

Discrepancy between stimulus response and tolerance of pain in Alzheimer disease.

BACKGROUND: Affective-motivational and sensory-discriminative aspects of pain were investigated in patients with mild to moderate Alzheimer disease (AD) and healthy elderly controls using the cold pressor test tolerance and repetitive stimuli of warmth and heat stimuli, evaluating the stimulus-response function. METHODS: A case-control design was applied examining 33 patients with mild to moderate AD dementia and 32 healthy controls with the cold pressor test (4°C). Warmth detection threshold (WDT) and heat pain threshold (HPT) were assessed using 5 stimulations. A stimulus-response function was estimated using 4 incrementally increasing suprathreshold heat stimuli. RESULTS: Cold pressor tolerance was lower in patients with AD dementia than in controls (p = 0.027). There were no significant differences between groups regarding WDT and HPT. Significant successive increases in HPT assessments indicated habituation (p < 0.0001), which was similar in the 2 groups (p = 0.85). A mixed model for repeated measures demonstrated that pain rating of suprathreshold stimuli depended on HPT (p = 0.0004) and stimulus intensity (p < 0.0001). Patients with AD dementia had significantly lower increases in pain ratings than controls during suprathreshold stimulation (p = 0.0072). CONCLUSION: Our results indicate that AD dementia is not associated with a propensity toward development of sensitization or a lack of habituation, suggesting preservation of sensory-discriminative aspects of pain perception. The results further suggest that the attenuated cold pressor pain tolerance may relate to impairment of coping abilities. Paradoxically, we found an attenuated stimulus-response function, compared to controls, suggesting that AD dementia interferes with pain ratings over time, most likely due to memory impairment.