Cognitive Decline, Dementia, Alzheimer's and….hope?nevadaosteopathic.org/...CognitiveImpairment.pdf · 1.Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive

Cognitive Decline, Dementia, Alzheimer's and….hope?Robert Adams D.O. AOBFP, IFMCP

Declaration of Conflict of InterestsNone

Objectives

1. Define cognitive impairment vs dementia vs Alzheimer's type dementia

2. Tools for assessing and defining cognitive decline and dementia

3. Social, economic burden of Alzheimer’s 4. Pathophysiology of Alzheimer's Dementia5. Discuss novel, intensive protocol demonstrating measures

of improvement.

Cognitive Impairment

1. Change from baseline noticed by patient + knowledgeable informant + Clinical Cognitive Assessment Tool

2. Notice deficit in 1 of 5 settings a. Acquire & remember new informationb. Visual Spatialc. Reasoning/Judgment complex tasksd. Languagee. Personality behavior

3. Maintains independence in social and occupational functioning

4. Not due to other medical or psychological condition

Dementia1) Patient + knowledgeable informant + Clinical

Cognitive Assessment Tool2) Deficit in at least 2 of 5 settings

a) Acquire & remember new informationb) Visual Spatialc) Reasoning/Judgment complex tasksd) Languagee) Personality behavior

3) Interference with the ability to function at work or at usual activities

4) Not due to other medical or psychological condition

1. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270-9.2. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-9.3. Sperling, Reisa A. et al., Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association , Volume 7 , Issue 3 , 280 - 292

Cognitive Impairment

1. Change from baseline noticed by patient + knowledgeable informant + Clinical Cognitive Assessment Tool

2. Notice deficit in 1 of 5 settings a. Acquire & remember new informationb. Visual Spatialc. Reasoning/Judgment complex tasksd. Languagee. Personality behavior

3. Maintains independence in social and occupational functioning

4. Not due to other medical or psychological condition

SCI = Subjective Cognitive Impairment(Patient notices change)

MCI = Mild Cognitive Impairment(Patient and close associate notice change)

1. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270-9.2. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-9.3. Sperling, Reisa A. et al., Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association , Volume 7 , Issue 3 , 280 - 292

Clinical Cognitive Assessment tools per AOA online training-“On the Front lines with Alzheimer's Dementia: Diagnosis and Management”

Mini CogMontreal Cognitive Assessment (MoCA)St. Louis University Mental Status (SLUMS)

https://aoaonlinelearning.osteopathic.org/mod/page/view.php?id=674

Mini cog! Clock drawing and 3 word

recall! Quick (2-3) min! Visuospatial, Word recall,

executive function! 0-2 high likelihood of dementia,

3-5 low likelihood of dementia

Simons, B. et al. Evaluation of suspected Dementia. Am Fam Physician. 2011 Oct 15;84(8):895-902.

St Louis University Mental Status (SLUMS)

Approximately 10 min to administer

Orientation, short term memory, naming objects, calculations, clock drawing, geometric shape recognition

Scoring: See scaleEducation impacts scoring

Montreal Cognitive Assessment (MOCA)10-15 min to administerTests visuospatial/executive, naming,

memory, attention, language, abstraction, delayed recall and orientation

26-30 is normal, 18-26 mild cognitive impairment, 11-17 mild dementia, 6-10 moderate dementia, <6 severe dementia

Sensitive for dementiaTechnical to administerEducational adjustment (+1 for high

school education or less)

https://kateswaffer.com/2016/09/22/what-is-dementia-part-3/


https://www.alzwisc.org/Types%20of%20dementia.htm https://gdblogs.shu.ac.uk/b2027135/2013/11/13/different-types-of-dementia/

https://qbi.uq.edu.au/brain/dementia/types-dementia

Criteria for Alzheimer's: NIA-AADementia diagnosis with Insidious onset + Gradual worsening and:

Amnestic onset! Acquire and remember new information,

Personality, Behavior, Comportment

Evidence of CVD/stroke

Medical or neurologic Diagnosis affecting cognition

Medication affecting cognition

Features of non Alzheimer's Dementia

Non-Amnestic! Visiospatial, Language,

Reasoning, Judgement, Complex tasks

OR

Not in the setting of:

1.Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270-9.2. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-9.3. Sperling, Reisa A. et al., Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association , Volume 7 , Issue 3 , 280 - 292

Dementia Diagnosis: NIA-AA

Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2018 14, 535-562DOI: (10.1016/j.jalz.2018.02.018) Copyright © 2018 The Authors Terms and Conditions

Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2018 14, 535-562DOI: (10.1016/j.jalz.2018.02.018)

This staging scheme reflects the sequential evolution of AD from an initial stage characterized by the appearance of abnormal AD biomarkers in asymptomatic individuals. As biomarker abnormalities progress, the earliest subtle symptoms become detectable. Further progression of biomarker abnormalities is accompanied by progressive worsening of cognitive symptoms, culminating in dementia

6 Stages of Alzheimer's

Stage 1:! Cognitive tests normal! Patient-no decline in cognition/neurobehavior sx! Observer-no decline in cognition/neurobehavioral sx

Stage 2! Cognitive tests normal! Decline in previous level of cognition noted by patient or

observer! May have neurobehavioral symptoms! No functional impact on daily life Alzheimer's & Dementia: The Journal of

the Alzheimer's Association 2018 14, 535-562DOI: (10.1016/j.jalz.2018.02.018)

6 stages of Alzheimer's (cont)Stage 3! Cognitive tests show impairment! Decline in previous level of cognition noted by patient or

observer! Cognitive presentation may not be primarily amnestic! Performs daily activities independentlyStage 4! Mild dementia! Substantial progressive cognitive impairment noted by

observer and/or patient! Clearly evident functional impact on daily life


6 stages of Alzheimer's (cont)

Stage 5! Moderate dementia! Progressive cognitive/neurobehavioral impairment ○ Extensive impact on daily life○ Requires frequent assistance

Stage 6! Severe dementia! Progressive cognitive/neurobehavioral impairment○ Interview may not be possible○ Complete dependence in basic activities


MRI - Magnetic resonance imaging

https://www.progressnp.com/article/neuroimaging-dementia-update-general-clinician/


FDG-PET Scan(Fluorodeoxyglucose Positron Emission Tomography Scan)

PET scans can detect the decline in glucose metabolism associated with decreased cognitive function, particularly in the temporal and parietal lobes located on the sides and the back of the brain, the regions associated with memory formation and language. UCBerkeley researchers are finding that brain imaging shows promise as a method of detecting early signs of Alzheimer's disease. On the left is a PET scan showing normal levels of glucose metabolism, indicated in yellow and red. The levels of glucose metabolism in the brain are decreased in patients with mild cognitive impairment (middle) and with Alzheimer's disease (right).Credit: Cindee Madison and Susan Landau, UC Berkeley

https://www.sciencedaily.com/releases/2009/07/090714085812.htm


Am-PET Scan(Amyloid Positron Emission Tomography Scan)

Amyloid PET scanning makes amyloid plaques "light up" on a brain PET scan, enabling, for the first time, accurate detection of plaques in living people.

https://radiology.ucsf.edu/patient-care/services/specialty-imaging/alzheimer


https://www.youtube.com/watch?time_continue=43&v=NjgBnx1jVIUBredesen DE (2014) Reversal of cognitive decline: A novel therapeutic program. Aging 6: 707-717

Quick facts(Patient statistics)

https://alz.org/alzheimers-dementia/facts-figures


Caregivers


Eighty-three percent of the help provided to older adults in the United States comes from family members, friends or other unpaid caregivers. Nearly half of all caregivers who provide help to older adults do so for someone with Alzheimer's or another dementia.

Who are the caregivers?

● About one in three caregivers (34 percent) is age 65 or older.● Approximately two-thirds of caregivers are women; more

specifically, over one-third of dementia caregivers are daughters.

● Approximately one-quarter of dementia caregivers are "sandwich generation" caregivers — meaning that they care not only for an aging parent, but also for children under age 18.


While there is no cure for Alzheimer’s disease or a way to stop or slow its progression, there are drug and non-drug options that may help treat

symptoms. Understanding available options can help individuals living with the disease and their caregivers to cope with symptoms and improve

quality of life.

https://www.alz.org/alzheimers-dementia/treatments

Extensive preclinical studies from numerous laboratories have identified multiple pathogenetic targets for potential intervention. These include, in addition to amyloid-β (Aβ) oligomers and tau, inflammatory mediators, apolipoproteins and lipid metabolism factors, hormonal mediators, trophic factors and their receptors, calcium regulatory pathways, axoplasmic transport machinery, neurotransmitters and their receptors, prion protein, and a host of other potential targets. However, one of the drawbacks of these preclinical studies is that many have implicated single pathways, and shown large effects of targeting one pathway, whereas in human studies, such approaches have not been borne out.

Bredesen DE (2014) Reversal of cognitive decline: A novel therapeutic program. Aging 6: 707-717.

There are several possible inferences from such discrepant results:

! first, it is possible that it will be necessary to target multiple pathways simultaneously in order to effect an improvement in symptoms and pathophysiology.

! Second, it is possible that targeting a single pathway will be sufficient, but that earlier intervention will be required.

! Third, it is possible that all of these seemingly disparate pathways will converge on a single critical pathway, so that either a single targeted therapy or a multi-component, multi-targeted approach may be effective.

! And fourth, of course it is possible that neither of these two types of approaches will be sufficient.


While there is no cure for Alzheimer’s disease or a way to stop or slow its progression, there are drug and non-drug options that may help treat

symptoms. Understanding available options can help individuals living with the disease and their caregivers to cope with symptoms and improve

quality of life.


The Tenets of Osteopathic Medicine express the underlying philosophy of osteopathic medicine and were approved by the AOA House of Delegates as policy.

1. The body is a unit; the person is a unit of body, mind, and spirit.

2. The body is capable of self-regulation, self-healing, and health maintenance.

3. Structure and function are reciprocally interrelated.

4. Rational treatment is based upon an understanding of the basic principles of body unity, self-regulation, and the interrelationship of structure and function.

https://osteopathic.org/about/leadership/aoa-governance-documents/tenets-of-osteopathic-medicine/

Tenets of Osteopathic

Medicine

The Tenets of Osteopathic Medicine express the underlying philosophy of osteopathic medicine and were approved by the AOA House of Delegates as policy.

1. The body is a unit; the person is a unit of body, mind, and spirit.

2. The body is capable of self-regulation, self-healing, and health maintenance.

3. Structure and function are reciprocally interrelated.

4. Rational treatment is based upon an understanding of the basic principles of body unity, self-regulation, and the interrelationship of structure and function.


Tenets of Osteopathic

Medicine

Based on a combination of in vitro and in vivo studies, we have advanced a model in which AD results from an imbalance in endogenous plasticity signaling (Fig. 1), [5-9], and in which the β-amyloid precursor protein (APP) is a mediator of such plasticity-related signaling.




The patient began on the following parts of the overall therapeutic system: (1) he fasted for a minimum of 3 hours a between dinner and bedtime, and fo a minimum of 12 hours between dinner and breakfast: (2) he eliminated simple carbohydrates and processed foods from his diet; (3) he increased consumption of vegetables and fruits, and limited consumption of fish to non-farmed, and meat to occasional grass-fed beef or organic chicken; (4) he took probiotics; (5) he took coconut oil i tsp bid; (6) he exercised strenuously, swimming 3-4 times a week; (7) he took melatonin 0.5 mg po qhs, and tried to sleep as close to 8 hours per night as his schedule would allow; (8) he took herbs Bacopa monniera 250 mg, Ashwaganda 500mg, and tumeric 400 mg each day; (9) he took Methylcobalamin 1 mg, methyltetrahydrofolate 0.8mg, and pyridoxine-5-phosphate 50 mg po bid; (11) he took vitamin C 1 g per day, Vitamin D3 5000IU per day, vitamin E 400Iu per day, CoQ10 200 mg per day, Zn picolinate 50 per day, and alpha-lipoic acid 100 mg per day; (12) he took DHA 320mg and EPA 180 mg per day.


A day in the life with the protocol

Obstacles to treatment


https://www.pinterest.com/pin/412994228306464692/?lp=true


1. Cognitive Traininga. Interventions aimed at enhancing

reasoning, memory, and speed of processing, to delay or slow age-related cognitive decline were found promising

2. Blood Pressurea. particularly in midlife, might prevent,

delay or slow clinical Alzheimer’s-type dementia

3. Physical Activitya. Citing the many known health

benefits of physical activity, the committee pointed to growing evidence that among these is the possible reduced risk of age-related cognitive decline

https://www.nih.gov/news-events/news-releases/national-academies-committee-sees-promising-inconclusive-evidence-interventions-prevent-cognitive-decline-dementia

Bredesen et al. (2018) Reversal of Cognitive Decline:100. J Alzheimers Dis Parkinsonism 2018, 8:5



This model suggests that the probability of developing Alzheimer’s disease is proportional to the ratio of synaptoclastic signaling to synaptoblastic signaling.

Some examples include: 1. Identifying and treating pathogens such as Borrelia, Babesia,

or Herpes family viruses:2. Identifying gastrointestinal hyperpermeability, repairing the

gut, a enhancing the microbiome;3. Identifying insulin resistance and protein glycation, and

returning insulin sensitivity and reduced protein glycation;4. Identify and correct suboptimal nutrient, hormone, or trophic

support (including vascular support);5. Identifying toxins (metallotoxins and other inorganics,

organic toxins, or biotoxins), reducing toxic exposure and detoxifying.

Since each patient has a different combination of the many potential contributors to cognitive decline, the approach to treatment is targeted and personalized.


Outcomes


KeyAm-PET = Amyloid Positron Emission Tomography Scan

CNS-VS = CNS Vital Signs;

CVLT: California Verbal Learning Test

FDG-PET = Fluorodeoxyglucose Positron Emission Tomography Scan

HC = Hippocampus

MCI = Mild Cognitive Impairment

MMSE = Mini-Mental Status Exam

MoCA = Montreal Cognitive Assessment

NP = Neuropsychiatric testing

Age/Gender APOE status Symptom Diagnosis Imaging Cognitive measurement Outcome

MRI - Magnetic resonance imaging



Quantitative analysis of brain structure volumes

Discussion


Discussion


Discussion


Controversie

Hellmuth J, Rabinovici GD, Miller BL. The Rise of Pseudomedicine for Dementia and Brain Health. JAMA.2019;321(6):543–544. doi:10.1001/jama.2018.21560

-https://jamanetwork.com/journals/jama/article-abstract/2723294

Recently, detailed protocols to reverse cognitive changes have been promoted, but these protocols merely repackage known dementia interventions (eg, cognitive training, exercise, a heart healthy diet) and add supplements and other lifestyle changes. Such protocols are promoted by medical professionals with legitimate credentials, offer a unique holistic and personal approach and are said to be based on rigorous data published in reputable journals. However, when examining the primary data, the troubling and familiar patterns of testimony and cargo cult science emerge. The primary scientific articles superficially appear valid, yet lack essential features, such as sufficient participation characterization, uniform interventions, or treatment randomization with control or placebo groups, and may fail to include sufficient study limitations. Some of these poor-quality studies may be published in predatory open access journals.”

“A similarly concerning category of pseudomedicine involves interventions promoted licensed medical professionals that target unsubstantiated etiologies of neurodegenerative disease (eg, metal toxicity; mold exposure’ infectious causes, such as Lyme disease).”

Controversie - moreThe possibility that Alzheimer’s disease (AD) has a microbial etiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae….Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi….Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals.

Pisa, D. et al. Different Brain Regions are Infected with Fungi in Alzheimer's Disease. Sci. Rep. 5, 15015; doi: 10.1038/srep15015 (2015).

Conclusion1. Cognitive Decline is on a continuum with dementia and there are several

different diagnoses that lead to dementia. 2. Alzheimers dementia is the most common cause of dementia and leads to

general decline of cognition.3. The social impacts are significant and the economic burdens are expected to

increase.4. This has been an untreatable disease that has not responded to monotherapy

interventions5. Therapeutic intervention systems directed at decreasing insulting signals and

increasing the trophic signals for amyloid precursor protein (APP) have shown some favorable changes in symptoms with some patients having Alzheimer's dementia.

ReferencesAlbert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270-9.

McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-9.

Sperling, Reisa A. et al., Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association , Volume 7 , Issue 3 , 280 - 292


Simons, B. et al. Evaluation of suspected Dementia. Am Fam Physician. 2011 Oct 15;84(8):895-902.

https://www.alzwisc.org/Types%20of%20dementia.htm

https://gdblogs.shu.ac.uk/b2027135/2013/11/13/different-types-of-dementia/


Bredesen DE (2014) Reversal of cognitive decline: A novel therapeutic program. Aging 6: 707-717


https://www.alzwisc.org/Types%20of%20dementia.htm


Referenceshttps://www.youtube.com/watch?time_continue=43&v=NjgBnx1jVIU


https://www.alz.org/alzheimers-dementia/treatmentshttps://osteopathic.org/about/leadership/aoa-governance-documents/tenets-of-osteopathic-medicine







Pisa, D. et al. Different Brain Regions are Infected with Fungi in Alzheimer's Disease. Sci. Rep. 5, 15015; doi: 10.1038/srep15015 (2015).

https://www.youtube.com/watch?time_continue=43&v=NjgBnx1jVIU









References


Hellmuth J, Rabinovici GD, Miller BL. The Rise of Pseudomedicine for Dementia and Brain Health. JAMA.2019;321(6):543–544. doi:10.1001/jama.2018.21560

-https://jamanetwork.com/journals/jama/article-abstract/2723294

https://jamanetwork.com/journals/jama/article-abstract/2723294

Documents

Cognitive Decline, Dementia, Alzheimer's and….hope?nevadaosteopathic.org/...CognitiveImpairment.pdf · 1.Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive