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Dual sensory impairment: Global prevalence, future projections, and its association with cognitive decline

ALZHEIMERS & DEMENTIA 2025年第2期21卷 e14465页

作者： Yeo, Brian Sheng Yep Gao, Esther Yanxin Tan, Benjamin Kye Jyn Ong, Benedict Ding Chao Cho, Ryan Wei Yang Lim, Chee Yit Man, Ryan Eyn Kidd Fenwick, Eva K. Gupta, Preeti Chen, Christopher Li-Hsian Chew, Samuel Teong Huang Teo, Neville Wei Yang Toh, Song Tar Ng, Jia Hui Tan, Vanessa Yee Jueen Lamoureux, Ecosse L. Natl Univ Singapore Yong Loo Lin Sch Med Singapore Singapore Singapore Gen Hosp Dept Otorhinolaryngol Head & Neck Surg Singapore Singapore Sengkang Gen Hosp Dept Otorhinolaryngol Head & Neck Surg Singapore Singapore Duke NUS Med Sch SingHlth Duke NUS Surg Acad Clin Program Singapore Singapore Singapore Natl Eye Ctr Singapore Eye Res Inst Singapore Singapore Duke NUS Med Sch Ophthalmol & Visual Sci Acad Clin Programme Singapore Singapore Duke NUS Med Sch Hlth Serv & Syst Res Dept Singapore Singapore Natl Univ Singapore Memory Aging & Cognit Ctr Yong Loo Lin Sch Med Dept Pharmacol Singapore Singapore Natl Univ Singapore Hosp Dept Psychol Med Singapore Singapore Changi Gen Hosp Dept Geriatr Med Singapore Singapore Singhealth Duke NUS Med Acad Clin Programme Singapore Singapore Univ Melbourne Fac Med Dent & Hlth Sci Melbourne Vic Australia

There is rising public health concern surrounding dual sensory impairment (DSI), or comorbid hearing and vision impairments. Its global prevalence and the magnitude of its association with cognitive decline (CD) is unclear. Three databases were searched for epidemiological studies examining DSI prevalence or its association with CD. Independent reviewers selected studies, extracted data, and evaluated bias. Random-effects meta-analyses were performed. Projections were estimated using United Nations data. The population attributable fraction of DSI-associated CD was calculated. Among 43 studies with 5,246,796 participants, clinically assessed DSI prevalence was 5.50% (95% confidence interval [CI] = 2.88%-10.26%), with regional/ethnic/age variations. DSI prevalence is projected to increase by 27.2% from 2025 to 2050. Approximately 59.83% (95%CI = 41.03-76.12) of DSI patients had cognitive impairment. Baseline DSI was associated with incident CD (odds ratio [OR] = 1.72, 95%CI = 1.37-2.15). Globally, 3.81% (95%CI = 1.05-10.55) of incident CD may be attributed to DSI. DSI is globally prevalent, growing, and associated with CD, highlighting the need for better health policy and resource *** The global prevalence of DSI is 5.50%, with geographical, ethnical and age variations. The prevalence of DSI rises with age and is projected to increase by 27.2% by 2050. Approximately 60% of individuals with DSI may have measurable cognitive impairment. DSI was associated with a 72% greater longitudinal risk of incident CD. Globally, 3.81% of CD cases may be attributable to DSI.

关键词： cognitive decline cognitive impairment dementia dual sensory impairment hearing impairment public health vision impairment

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Zolpidem Extended Release for Insomnia in Older Adults

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CURRENT PSYCHIATRY REPORTS 2009年第1期11卷 3-3页

作者： Ownby, Raymond L. Univ Miami Miller Sch Med Memory Disorders Program Ctr Aging Coral Gables FL 33124 USA

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Preliminary Evidence for Perturbation-Based tACS-EEG Biomarkers of Gamma Activity in Alzheimer's Disease

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INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY 2025年第1期40卷 e70025页

作者： Palmisano, Annalisa Pezanko, Luke R. Cappon, Davide Tatti, Elisa Macone, Joanna Koch, Giacomo Smeralda, Carmelo L. Romanella, Sara M. Ruffini, Giulio Rivolta, Davide Press, Daniel Z. Pascual-Leone, Alvaro El-Fakhri, Georges Santarnecchi, Emiliano Harvard Med Sch Massachusetts Gen Hosp Gordon Ctr Med Imaging Precis Neurosci & Neuromodulat Program Boston MA 02115 USA Harvard Med Sch Berenson Allen Ctr Noninvas Brain Stimulat Beth Israel Deaconess Med Ctr Boston MA 02115 USA Univ Bari Aldo Moro Dept Educ Psychol & Commun Bari Italy TUD Dresden Univ Technol Chair Lifespan Dev Neurosci D-01069 Dresden Germany CUNY Sch Med New York NY USA Santa Lucia Fdn Rome Italy Univ Siena Siena Brain Invest & Neuromodulat Lab Neurol & Clin Neurophysiol Sect Dept Med Surg & Neurosci Siena Italy Neuroelect Barcelona Barcelona Spain Hebrew SeniorLife Hinda & Arthur Marcus Inst Aging Res Boston MA USA Deanna & Sidney Wolk Ctr Memory Hlth Boston MA USA Harvard Med Sch Dept Neurol Boston MA USA Yale Univ Sch Med Dept Radiol & Biomed Imaging Dept Biomed Informat & Data Sci New Haven CT USA

BackgroundAlzheimer's disease (AD) is characterized by impaired inhibitory circuitry and GABAergic dysfunction, which is associated with reduced fast brain oscillations in the gamma band (gamma, 30-90 Hz) in several animal models. Investigating such activity in human patients could lead to the identification of novel biomarkers of diagnostic and prognostic value. The current study aimed to test a multimodal "Perturbation-based" transcranial Alternating Current Stimulation-Electroencephalography (tACS)-EEG protocol to detect how responses to tACS in AD patients correlate with patients' clinical phenotype. MethodsFourteen participants with mild to moderate dementia due to AD underwent a baseline assessment including cognitive status, peripheral neuroinflammation, and resting-state (rs)EEG. The tACS-EEG recordings included brief (6 ') tACS blocks of gamma (i.e., 40 Hz) stimulation administered through 4 different montages, with Pre/Post 32-Channels EEG for each block. Changes in tACS-EEG and rsEEG gamma band power with respect to baseline were adopted as a metric of induction and compared with cognitive scores and neuroinflammatory biomarkers. ResultsWe found positive correlations between 40 Hz-induced gamma activity in fronto-central-parietal areas and patient cognitive status and negative ones with neuroinflammatory markers. Participants with greater cognitive impairment exhibited less gamma induction and higher peripheral neuroinflammation. The same analysis performed with spectral power from baseline rsEEG resulted in no significant correlations, promoting the value of tACS-based perturbation for capturing individual differences in pathology-related brain features. ConclusionsOur work suggests a link between tACS-induced gamma band spectral power and clinical severity, with weaker gamma induction corresponding to more severe clinical/cognitive impairment. This study provides preliminary support for the development of novel physiological biomarkers and therapeutic t

关键词： Alzheimer's disease biomarkers gamma activity transcranial alternating current stimulation

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Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial

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JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE 2025年第1期12卷 100016页

作者： Macfarlane, Stephen Grimmer, Timo Teo, Ken O'Brien, Terence Woodward, Michael Grunfeld, Jennifer Mander, Alastair Brodtmann, Amy Brew, Bruce J. Morris, Philip Short, Cathy Kurrle, Susan Lai, Rosalyn Bharadwaj, Sneha Drysdale, Peter Sturm, Jonathan Lewis, Simon J. G. Barton, David Kalafatis, Chris Sharif, Saif Perry, Richard Mannering, Nicholas Macsweeney, J. Emer Pearson, Stephen Evans, Craig Krishna, Vivek Thompson, Alex Munisamy, Malathy Bhatt, Neel Asher, Aliya Connell, Sandra Lynch, Jennifer Rutgers, Sterre Malou Dautzenberg, Paul L. J. Prins, Niels Oschmann, Patrick Froelich, Lutz Tacik, Pawel Peters, Oliver Wiltfang, Jens Henri-Bhargava, Alexandre Smith, Eric Pasternak, Stephen Frank, Andrew Chertkow, Howard Ingram, Jennifer Hsiung, Ging-Yuek Robin Brittain, Rodney Tartaglia, Carmela Cohen, Sharon Villa, Luca M. Gordon, Elizabeth Jubault, Thomas Guizard, Nicolas Tucker, Amanda Kaufmann, Walter E. Jin, Kun Chezem, William R. Missling, Christopher U. Sabbagh, Marwan N. HammondCare Dementia Ctr Melbourne Vic Australia Tech Univ Munich Sch Med & Hlth Klinikum Rechts Isar Munich Germany Monash Univ Alfred Hosp Sch Translat Med Dept Neurosci Melbourne Vic Australia Univ Melbourne & Austin Hlth Ivanhoe Vic Australia Peninsula Therapeut & Res Grp Pty Ltd Frankston Vic Australia Geelong Private Med Ctr Geelong Vic Australia Royal Melbourne RMH Parkville Vic Australia Monash Univ Eastern Clin Res Unit Box Hill Vic Australia St Vincents Hosp Sydney Darlinghurst NSW Australia Gold Coast Memory Disorders Clin Southport Qld Australia Queen Elizabeth Hosp Woodville South SA Australia Hornsby Ku Ring Gai Hosp Hornsby NSW Australia KaRa MINDS Macquarie Pk NSW Australia Australian Alzheimers Res Org Nedlands WA Australia Delmont Private Hosp Glen Iris Vic Australia Cent Coast Neurosci Res Tumbi Umbi NSW Australia Univ Sydney Brain & Mind Ctr Camperdown NSW Australia NeuroCentrix Noble Pk Vic Australia Kings Coll London London England Southern Hlth NHS Fdn Trust Memory Assessment & Re Southampton England Imperial Coll Healthcare NHS Trust London England ReCognit Hlth Guildford England ReCognit Hlth London England ReCognit Hlth Plymouth England MAC Clin Res Barnsley England MAC Clin Res Blackpool England MAC Clin Res Cannock England MAC Clin Res Leeds England MAC Clin Res Liverpool England MAC Clin Res Manchester England MAC Clin Res Stockton On Tees England Glasgow Memory Clin Motherwell Scotland Brain Res Ctr Amsterdam Netherlands Brain Res Ctr Den Bosch Netherlands Brain Res Ctr Zwolle Netherlands Klinikum Bayreuth Bayreuth Germany Cent Inst Mental Hlth CIMH Mannheim Germany Univ Hosp Bonn Bonn Germany Charite Univ Med Berlin Berlin Germany Clin Psychotherapy Gottingen Germany Vancouver Island Hlth Author Victoria BC Canada Univ Calgary Hlth Brain Aging Labs Calgary AB Canada Western Univ Parkwood Inst London ON Canada Bruyere Continuing Care Ottawa ON Canada BayCrest Hlth Sc

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD). Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX (R) 2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement. Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial. Setting: Multicenter - 52 medical research centers/hospitals in 5 countries. Intervention: 508 participants with early AD (Stage 3) were randomized to receive either blarcamesine (n = 338) in medium dose group 30 mg or in high dose group 50 mg or placebo (n = 170) oral capsules once daily for 48 weeks. Participants in these groups were offered to enroll into the open-label-extension study ATTENTION-AD, which completed June 2024, *** Identifier NCT04314934. Measurements: The co-primary cognitive and functional outcomes were assessed as change in ADAS-Cog13 and ADCS-ADL from baseline to 48 weeks. The outcomes include the secondary outcome CDR-SB and biomarkers from the A/T/N spectrum, plasma A beta 42/40-ratio and global brain volume changes measured by MRI. All clinical endpoints were analyzed using mixed model for repeated measures (MMRM), plasma biomarker measurements were analyzed by Welch's t-test, and volumetric MRI scans were analyzed by general linear model. Results: Among 462 randomized participants in the intent-to-treat population (mean age, 73.7 years;225 [48.7%] women), 338 (73.2%) completed the trial. The co-primary outcome was met under the multiplicity control rule, since the differences in the least-squares mean (LSM) change from baseline to 48 weeks between the prespecified blarcamesine and placebo groups for ADAS-Cog13 was significant at a level of P < 0.025 and for CDR-SB was significant at a level of P < 0.025, while ADCS-ADL did not reach significance at Week

关键词： Blarcamesine Autophagy Sigma-1 receptor Randomized clinical trial

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CURRENT AND FUTURE TREATMENTS FOR ALZHEIMER'S DISEASE

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CNS SPECTRUMS 2009年第8期14卷 4-7页

作者： Salloway, Stephen Butler Hosp Memory & Aging Program Providence RI 02906 USA Brown Univ Warren Alpert Med Sch Providence RI 02912 USA

There are currently >5 million people in the United States who have been diagnosed with Alzheimer's disease. That prevalence rate is expected to triple as the population ages. The health and economic burden due to Alzheimer's disease is a worldwide problem, with some of the greatest burden coming from the developing world as people live longer in those societies. Throughout the world, the projected growth of Alzheimer's disease is dramatic. This is a worldwide public health problem of the highest order, and there is a compelling need to develop new treatments and methods of earlier diagnosis need to slow the progression of the disease and lessen its impact.

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Effects of Electrode Drift in Transcranial Direct Current Stimulation

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BRAIN STIMULATION 2015年第3期8卷 515-519页

作者： Woods, Adam J. Bryant, Vaughn Sacchetti, Daniela Gervits, Felix Hamilton, Roy Univ Florida Cognit Aging & Memory Clin Translat Res Program Dept Aging & Geriatr Res Inst Aging Gainesville FL 32610 USA Univ Penn Dept Neurol Lab Cognit & Neural Stimulat Ctr Cognit Neurosci Philadelphia PA 19104 USA

Background: Conventional transcranial direct current stimulation (tDCS) methods involve application of weak electrical current through electrodes encased in saline-soaked sponges affixed to the head using elastic straps. In the absence of careful preparation, electrodes can drift from their original location over the course of a tDCS session. Objective: The current paper investigates the influence of electrode drift on distribution of electric fields generated by conventional tDCS. Methods: MRI-derived finite element models of electric fields produced by tDCS were used to investigate the influence of incremental drift in electrodes for two of the most common electrode montages used in the literature: M1/SO (motor to contralateral supraorbital) and F3/F4 (bilateral frontal). Based on these models, we extracted predicted current intensity from 20 representative structures in the brain. Results: Results from separate RM-ANOVAs for M1/SO and F3/F4 montages demonstrated that 5% incremental drift in electrode position significantly changed the distribution of current delivered by tDCS to the human brain (F's > 8.6, P's < 0.001). Pairwise comparisons demonstrated that as little as 5% drift was able to produce significant differences in current intensity in structures distributed across the brain (P's < 0.03). Conclusions: Drift in electrode position during a session of tDCS produces significant alteration in the intensity of stimulation delivered to the brain. Elimination of this source of variability will facilitate replication and interpretation of tDCS findings. Furthermore, measurement and statistically accounting for drift may prove important for better characterizing the effects of tDCS on the human brain and behavior. (C) 2015 Elsevier Inc. All rights reserved.

关键词： Transcranial direct current stimulation Electrode drift MRI-Derived finite element models tDCS reproducibility Electrode placement

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Functional redundancy of the posterior hippocampi is selectively disrupted in non-demented older adults with β-amyloid deposition

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NeuroImage: Reports 2025年第2期5卷 100255-100255页

作者： Blujus, Jenna K. Cole, Michael W. Festa, Elena K. Buka, Stephen L. Salloway, Stephen P. Heindel, William C. Oh, Hwamee Department of Cognitive and Psychological Sciences Brown University Providence 02912 United States Center for Molecular & Behavioral Neuroscience Rutgers University Newark 07102 United States Department of Epidemiology and Population Health Brown University Providence 02912 United States Department of Psychiatry and Human Behavior Brown University Providence 02912 United States Memory and Aging Program Butler Hospital Providence 02906 United States Department of Neurology Brown University Providence 02912 United States Carney Institute for Brain Science Brown University Providence 02912 United States

Several neural mechanisms underlying resilience to Alzheimer's disease (AD) have been proposed, including redundant neural connections between the posterior hippocampi and all other brain regions, and global functional connectivity of the left frontal cortex (LFC). Here, we investigated if functional redundancy of the hippocampus (HC) and LFC underscores neural resilience in the presence of early AD pathologies. From the ADNI database, cognitively normal older adults (CN) (N = 220;36 % Aβ+) and patients with Mild Cognitive Impairment (MCI) (N = 143;51 % Aβ+) were utilized. Functional redundancy was calculated from resting state fMRI data using a graph theoretical approach by summing the direct and indirect paths (path lengths = 1–4) between each region of interest and its 263 functional connections. Posterior HC, but not anterior HC or LFC, redundancy was significantly lower in Aβ+ than Aβ-groups, regardless of diagnosis. Posterior HC redundancy related to higher education and better episodic memory, but it did not moderate the Aβ-cognition relationships across the diagnostic groups. Together, these findings suggest that posterior HC redundancy captures network disruption that parallels selective vulnerability to Aβ deposition. Further, our findings indicate that functional redundancy may underscore a network metric different from global functional connectivity of the LFC. © 2025

关键词： aging Alzheimer's disease Beta-amyloid plaques Functional magnetic resonance imaging Graph theory Resilience

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Contralateral delay activity tracks the influence of Gestalt grouping principles on active visual working memory representations

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ATTENTION PERCEPTION & PSYCHOPHYSICS 2015年第7期77卷 2270-2283页

作者： Peterson, Dwight J. Goezenman, Filiz Arciniega, Hector Berryhill, Marian E. Univ Missouri Dept Psychol Sci Memory & Cognit Aging Lab Columbia MO 65211 USA Univ Nevada Dept Psychol Program Cognit & Brain Sci Reno NV 89557 USA

Recent studies have demonstrated that factors influencing perception, such as Gestalt grouping cues, can influence the storage of information in visual working memory (VWM). In some cases, stationary cues, such as stimulus similarity, lead to superior VWM performance. However, the neural correlates underlying these benefits to VWM performance remain unclear. One neural index, the contralateral delay activity (CDA), is an event-related potential that shows increased amplitude according to the number of items held in VWM and asymptotes at an individual's VWM capacity limit. Here, we applied the CDA to determine whether previously reported behavioral benefits supplied by similarity, proximity, and uniform connectedness were reflected as a neural savings such that the CDA amplitude was reduced when these cues were present. We implemented VWM change-detection tasks with arrays including similarity and proximity (Experiment 1);uniform connectedness (Experiments 2a and 2b);and similarity/proximity and uniform connectedness (Experiment 3). The results indicated that when there was a behavioral benefit to VWM, this was echoed by a reduction in CDA amplitude, which suggests more efficient processing. However, not all perceptual grouping cues provided a VWM benefit in the same measure (e.g., accuracy) or of the same magnitude. We also found unexpected interactions between cues. We observed a mixed bag of effects, suggesting that these powerful perceptual grouping benefits are not as predictable in VWM. The current findings indicate that when grouping cues produce behavioral benefits, there is a parallel reduction in the neural resources required to maintain grouped items within VWM.

关键词： Visual working memory Gestalt principles Perceptual organization Contralateral delay activity

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Short-term estrogen treatment in ovariectomized rats augments hippocampal acetylcholine release during place learning

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NEUROBIOLOGY OF LEARNING AND memory 2003年第3期80卷 315-322页

作者： Marriott, LK Korol, DL Univ Illinois Dept Psychol & Neurosci Program Champaign IL 61820 USA Univ Arizona Arizona Res Labs Div Neural Syst Memory & Aging Tucson AZ 85721 USA

Estrogen modulates learning and memory in ovariectomized and naturally cycling female rats, especially in tasks using spatial learning and navigation. Estrogen also modulates cholinergic function in various forebrain structures. Past Studies have shown positive correlations between hippocampal ACh output and performance on hippocampus-dependent tasks. The present study examined whether estradiol replacement would potentiate hippocampal ACh release during place learning. In vivo microdialysis and HPLC were used to measure extracellular ACh levels in the hippocampus of ovariectomized female rats that had received s.c. injections of 17beta-estradiol (10 mug) or sesame oil (vehicle treatment) 48 and 24 h prior to training on a place task. Estrogen did not alter baseline levels of extracellular ACh in the hippocampus. During training, hippocampal ACh increased in ovariectomized rats regardless of estrogen status. However, while estradiol did not enhance learning in this experiment, estradiol significantly potentiated the increase in hippocampal ACh release seen during place training. This represents the first demonstration of on-line assessment of ACh output in hippocampus during learning in female rats and suggests that estrogen-dependent modulation of ACh release during training might control activation of different neural systems used during learning. (C) 2003 Elsevier Inc. All rights reserved.

关键词： ovariectomy microdialysis gonadal steroids acetylcholine hippocampus estradiol spatial memory

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Depression among Alzheimer's caregivers: Identifying risk factors

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American Journal of Alzheimer's Disease and other Dementias 2001年第6期16卷 353-359页

作者： Shua-Haim, Joshua R. Shi, Yong Kuo, Yen-Hong Smith, Juanita M. Memory Disorders Institute Meridian Institute for Aging Neptune NJ United States UMDNJ-SOM Stratford NJ United States Rutgers University New Brunswick NJ United States Memory Disorders Institute Meridian Institute for Aging Affiliated with Meridian Health System and Jersey Shore Medical Center Neptune NJ United States Memory Disorders Institute Meridian Institute for Aging Mid Atlantic Geriatric Fellowship Program Affiliated with Meridian Health System Jersey Shore Medical Center Neptune NJ United States Memory Disorders Institute Meridian Institute for Aging Neptune NJ United States

Purpose: The purpose of this study was to reveal risk factors contributing to the development of depression among caregivers of Alzheimer disease patients. Methods: In a cross-sectional study, all caregivers of consecutive Alzheimer's disease patients were asked to participate in the study. Patient and caregiver depression was evaluated by using the Yesavage Geriatric Depression Scale (GDS). Information regarding patients' functional status, driving status, and type of behavioral abnormalities was obtained from caregivers. Patients' functional status was evaluated by using the Katz Activity of Daily Living (ADL) scale. The Folstein Mini-Mental Status Examination (MMSE) was used to evaluate cognition. Risk factors for Alzheimer caregiver depression were assessed by means of logistic regression analysis. Results: A total of 92 patients and caregivers were evaluated. Fifteen were excluded due to incomplete data. A total of 77 pairs were included in this analysis. The age of caregivers ranged from 28 to 88 years. Mean (standard deviation [SD]) age was 63.1 (SD = 16.3) years old. Husbands and wives (caregivers) accounted for 49.4 percent;daughters or sons (or daughters- or sons-in-law) accounted for 42.9 percent. There were 29 caregivers (38 percent) found to be depressed. By using multivariate analysis, the following factors have been identified as risk factors for depression in Alzheimer's caregivers: depression in the dementia patient;ADL functional scores of 12 or greater;and the presence of hallucinations. Conclusion: Three risk factors were found to have a strong association with Alzheimer's caregiver depression. Early recognition of such risk factors may help to identify Alzheimer's caregivers with depression.

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