Targeting anticipatory neurogenesis to maintain cognitive reserve

Abstract Memory imprecision is a hallmark of age-related cognitive decline and mild-cognitive impairment (MCI) and is characterized by increased memory interference and decreased stability of memory representations. Evidence from humans, non-human primates and rodents demonstrate reduced hippocampal neurogenesis, excitation-inhibition imbalance and inflexible hippocampal remapping during age-related cognitive decline and MCI. Developing strategies to reverse cognitive decline during aging and Mild Cognitive Impairment necessitates an understanding of molecular, cellular, circuit and network mechanisms that support memory functions of the hippocampus. Over the last decade we have built a multifaceted program grounded in basic neuroscience that is aimed at improving memory in aging and MCI. We have demonstrated how we can Rejuvenate the aged hippocampus by selectively increasing neurogenesis and how we can Re-engineer connectivity of aged inhibitory microcircuits to improve memory precision in aging. Ongoing efforts include strategies to Repairing neurogenic niche fitness by targeting intercellular communication in the aging hippocampus. In today’s talk I will present a fourth approach catalyzed by our discovery of the first transcriptional regulator of neural stem cell expansion in the adult hippocampus. We will present data in support of this claim and convey how this discovery may guide strategies to maintain cognitive reserve embodied in the pool of neural stem cells in the adult hippocampus.

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Multimodal measurement approach to identify individuals with mild cognitive impairment: study protocol for a cross-sectional trial

BMJ Open ◽

10.1136/bmjopen-2020-046879 ◽

2021 ◽

Vol 11 (5) ◽

pp. e046879

Author(s):

Bernhard Grässler ◽

Fabian Herold ◽

Milos Dordevic ◽

Tariq Ali Gujar ◽

Sabine Darius ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Statistical Analysis ◽

Cognitive Decline ◽

Cognitive Performance ◽

Classification Accuracy ◽

Multimodal Approach ◽

Cross Sectional ◽

Age Related ◽

Age Related Cognitive Decline

IntroductionThe diagnosis of mild cognitive impairment (MCI), that is, the transitory phase between normal age-related cognitive decline and dementia, remains a challenging task. It was observed that a multimodal approach (simultaneous analysis of several complementary modalities) can improve the classification accuracy. We will combine three noninvasive measurement modalities: functional near-infrared spectroscopy (fNIRS), electroencephalography and heart rate variability via ECG. Our aim is to explore neurophysiological correlates of cognitive performance and whether our multimodal approach can aid in early identification of individuals with MCI.Methods and analysisThis study will be a cross-sectional with patients with MCI and healthy controls (HC). The neurophysiological signals will be measured during rest and while performing cognitive tasks: (1) Stroop, (2) N-back and (3) verbal fluency test (VFT). Main aims of statistical analysis are to (1) determine the differences in neurophysiological responses of HC and MCI, (2) investigate relationships between measures of cognitive performance and neurophysiological responses and (3) investigate whether the classification accuracy can be improved by using our multimodal approach. To meet these targets, statistical analysis will include machine learning approaches.This is, to the best of our knowledge, the first study that applies simultaneously these three modalities in MCI and HC. We hypothesise that the multimodal approach improves the classification accuracy between HC and MCI as compared with a unimodal approach. If our hypothesis is verified, this study paves the way for additional research on multimodal approaches for dementia research and fosters the exploration of new biomarkers for an early detection of nonphysiological age-related cognitive decline.Ethics and disseminationEthics approval was obtained from the local Ethics Committee (reference: 83/19). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.Trial registration numberClinicalTrials.gov, NCT04427436, registered on 10 June 2020, https://clinicaltrials.gov/ct2/show/study/NCT04427436.

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Dietary fatty acids, age-related cognitive decline, and mild cognitive impairment

The journal of nutrition health & aging ◽

10.1007/bf02982670 ◽

2008 ◽

Vol 12 (6) ◽

pp. 382-386 ◽

Cited By ~ 30

Author(s):

V. Solfrizzi ◽

C. Capurs ◽

A. D’Introno ◽

A. M. Colacicco ◽

V. Frisardi ◽

...

Keyword(s):

Fatty Acids ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Dietary Fatty Acids ◽

Age Related ◽

Age Related Cognitive Decline

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Lifestyles and Cognition

Integrative Journal of Medical Sciences ◽

10.15342/ijms.2021.399 ◽

2021 ◽

Vol 8 ◽

Author(s):

Shashi Agarwal

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Physical Inactivity ◽

Lifestyle Factors ◽

Poor Diet ◽

Age Related ◽

Modifiable Factors ◽

Age Related Cognitive Decline

Cognitive decline is a growing medical concern. It includes age-related cognitive decline, mild cognitive impairment, and dementia. Dementia results in considerable dysfunction in life and is associated with an increase in mortality. Since there is no cure at this time, attention is being increasingly directed towards prevention. Lifestyle factors, such as smoking, alcoholism, physical inactivity, poor diet, improper sleep, and loneliness are repeatedly being recognized as modifiable factors that can reduce cognitive decline. This manuscript briefly reviews the lifestyle-cognition relationship.

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Age-Related Cognitive Decline and Prevalence of Mild Cognitive Impairment in the Iwaki Health Promotion Project

Journal of Alzheimer s Disease ◽

10.3233/jad-210699 ◽

2021 ◽

pp. 1-13

Author(s):

Naoko Nakahata ◽

Takumi Nakamura ◽

Takeshi Kawarabayashi ◽

Yusuke Seino ◽

Sadanobu Ichii ◽

...

Keyword(s):

Health Promotion ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Mixed Model ◽

Linear Mixed Model ◽

Educational History ◽

Dementia Patients ◽

Age Related ◽

Age Related Cognitive Decline

Background: The Iwaki Health Promotion Project (IHPP) is a community-based study for the prevention of lifestyle-related diseases and improvement of quality of life. Objective: Between 2014 and 2017, a total of 4,442 Iwaki town residents from 19 to 93 years of age participated in annual surveys to clarify the natural course of age-related cognitive decline and mild cognitive impairment (MCI). Methods: Modified OLD and SED-11Q questionnaires, MMSE, Logical Memory II, educational history, and APOE genotypes were examined at the first screening. MCI and dementia were diagnosed at the second examination by detailed neurological examination, CDR, and MRI, and followed for 3 years. Spline regression analyses based on a linear mixed model was adopted for statistical analysis. Results: MMSE scores declined with age from 55 to 64 years. There was also interaction between levels of education and ages. At the second examination, 56 MCI and 5 dementia patients were identified. None of the MCI cases progressed to dementia during the 3 years. During follow-up examinations, 13 cases showed improved MMSE scores (0.95 point/year), 5 remained stable, and 7 deteriorated (–0.83 point/year). Five cases showed improved CDR-SOB scores (–0.28 point/year), 9 remained stable, and 6 deteriorated (0.3 point/year). Conclusion: IHPP revealed that age- and education-related cognitive decline began and advanced from 55 years of age. The prevalence of MCI and dementia was estimated to be 5.9%in the Iwaki town cohort over 60 yeas of age. About 30%of MCI cases showed progression of cognitive decline.

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