Stemming the Alzheimer tsunami: introduction to the special issue on reserve and resilience in Alzheimer’s disease

Okonkwo, Ozioma C.; Vemuri, Prashanthi

doi:10.1007/s11682-017-9677-z

Cited by 5 publications

(5 citation statements)

References 21 publications

(21 reference statements)

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“…Two related concepts, brain reserve and cognitive reserve, have been cited as mechanisms to explain resilience, although the terms are often used interchangeably in the literature [9]. Reserve is proposed to moderate between brain measures and cognition.…”

Section: Introductionmentioning

confidence: 99%

Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study

et al. 2019

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Background There is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer’s disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging. Methods We included 550 older adults participating in the Whitehall II study with longitudinal data, cognitive test results, and multi-modal MRI. Hippocampal atrophy was defined as Scheltens Scores >0. Resilient individuals (n = 184) were defined by high cognitive performance despite hippocampal atrophy (HA). Non-resilient participants (n = 133) were defined by low cognitive performance (≥1.5 standard deviations (S.D.) below the group mean) in the presence of HA. Dynamic and static exposures were evaluated for their ability to predict later resilience status using multivariable logistic regression. In a brain-wide analysis we tested for group differences in the integrity of white matter (structural connectivity) and resting-state networks (functional connectivity). Findings Younger age (OR: 0.87, 95% CI: 0.83 to 0.92, p<0.001), higher premorbid FSIQ (OR: 1.06, 95% CI: 1.03 to 1.10, p<0.0001) and social class (OR 1 vs. 3: 4.99, 95% CI: 1.30 to 19.16, p = 0.02, OR 2 vs. 3: 8.43, 95% CI: 1.80 to 39.45, p = 0.007) were independently associated with resilience. Resilient individuals could be differentiated from non-resilient participants by higher fractional anisotropy (FA), and less association between anterior and posterior resting state networks. Higher FA had a significantly more positive effect on cognitive performance in participants with HA, compared to those without. Conclusions Resilient individuals could be distinguished from those who developed impairments on the basis of sociodemographic characteristics, brain structural and functional connectivity, but not midlife lifestyles. There was a synergistic deleterious effect of hippocampal atrophy and poor white matter integrity on cognitive performance. Exploiting and supporting neural correlates of resilience could offer a fresh approach to postpone or avoid the appearance of clinical symptoms.

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Section: Introductionmentioning

confidence: 99%

Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study

et al. 2019

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“…The importance of identifying factors that confer resilience is gaining increased recognition given the current lack of curative therapies for AD. 49 The identification of new genetic variants that modify AD risk will potentially uncover novel molecular targets. This line of research is poised to identify complementary pathways for curbing AD progression and delaying symptom onset.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we offer a glimpse into how one genetic factor, KLOTHO , offers resilience against age‐related changes in cognition and CSF tau. The importance of identifying factors that confer resilience is gaining increased recognition given the current lack of curative therapies for AD 49 . The identification of new genetic variants that modify AD risk will potentially uncover novel molecular targets.…”

Section: Discussionmentioning

confidence: 99%

AD‐associated CSF biomolecular changes are attenuated in KL‐VS heterozygotes

Driscoll

Lose

et al. 2022

Alz & Dem Diag Ass & Dis Mo

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Introduction Dementia as an inevitable aging consequence has been challenged and underscores the need for investigations of the factors that confer resilience. We examine whether the functionally advantageous KL‐VS variant of the putative aging suppressor KLOTHO gene attenuates age‐related cognitive decline and deleterious biomolecular changes. Methods Trajectories of change in memory and executive function ( N = 360; 2–12 visits) and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers—amyloid beta (Aβ)42, total tau (t‐tau), phosphorylated tau (p‐tau) ( N = 112; 2–4 samplings)—were compared between KL‐VS non‐carriers and heterozygotes in middle‐aged and older adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center studies. Results Memory and executive function declined ( p ’s 0.001) and CSF t‐tau, p‐tau, t‐tau/Aβ42, and p‐tau/Aβ42 levels increased (all p ’s 0.004) with age. The rate of p‐tau accumulation was attenuated for KL‐VS heterozygotes ( p = 0.03). Discussion KL‐VS heterozygosity may confer resilience to AD‐associated biomolecular changes.

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“…Importantly, older adults with older ‘subjective age’ or age identities were at greater risk of psychiatric and physical effects of isolation as a result of the COVID-19 pandemic [ 37 ]. The protective features of social, mental, and occupational stimulation on cognitive reserve and resilience have been well-established [ 38 ]. Lea et al found that cognitive enhancement among ‘personal development’ and ‘mental health’ as motivations for microdosing psychedelics (55% psilocybin) [ 39 ].…”

Section: Updates: Psilocybin For Palliative Carementioning

confidence: 99%

Psilocybin in Palliative Care: An Update

et al. 2023

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Purpose of Review This review article summarizes clinically and socially relevant developments over the past five years in the therapeutic use of the classical tryptamine psychedelic substance psilocybin, with respect to the common challenges faced by palliative care patients and their care teams. Psilocybin is available in whole fungal and isolated forms but is not yet approved for therapeutic use in the United States. Using targeted database and gray literature searches, and author recall, key sources were identified, reviewed, and synthesized as to the safety and efficacy of psilocybin in palliative care. Recent Findings Life-threatening or life-limiting illnesses and faced by palliative care patients are comorbid with emotional and spiritual distress. Research and field reports reviewed suggest that psilocybin has significant and in some cases, sustained anxiolytic, antidepressant, anti-inflammatory and entheogenic effects with a favorable safety profile. Limitations of the research include the risk for selection bias toward healthy, white, financially privileged individuals, and in general, follow-up timelines too short to appropriately evaluate durability of outcomes in psychospiritual benefits and quality of life. Summary While more research is needed for palliative care populations specifically, reasonable inferences can be made regarding the potential for benefit to palliative care patients from psilocybin’s demonstrated anxiolytic, antidepressant, anti-inflammatory and entheogenic effects. However, major legal, ethical and financial barriers to access exist for the general population; obstacles which are likely worsened for geriatric and palliative care patients. Empiric treatment and large-scale controlled trials of psilocybin should be conducted to further investigate the findings of the smaller studies reviewed here across a variety of populations, for a greater understanding of therapeutic benefit and clinically relevant safety criteria, and to support thoughtful legalization and medical access.

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Stemming the Alzheimer tsunami: introduction to the special issue on reserve and resilience in Alzheimer’s disease

Cited by 5 publications

References 21 publications

Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study

Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study

AD‐associated CSF biomolecular changes are attenuated in KL‐VS heterozygotes

Psilocybin in Palliative Care: An Update

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