Diversity in Cognitive Aging Quiz 2

normal aging

age-relative cognition declines, but is never impaired

impaired cognition score on normal distribution

bottom 16%

pathological aging

when people perform in the impaired range on 1 or more cognitive tests within a cognitive domain

dementia

syndrome associated with changes in thinking, emotions, and behavior that impair an individual’s capacity for independent living

syndrome

a constellation of signs and symptoms that often occur together

sign

objective measurable phenomenon observed by another person

symptom

subjective experience of individual affected

major neurocognitive disorder

-evidence of significant cognitive decline in 1 or more cognitive domains based on:

1. concern of the individual, a knowledgeable informant, or the clinician

2. a substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing

-the cognitive deficits interfere with capacity for independence in everyday activities

-synonymous with the term dementia

mild cognitive impairment (MCI)

-term used to describe the condition of individuals whose cognition lies between the cognitive changes of normal aging and early dementia

-patient has objective evidence of cognitive impairment that represents a decline from the past, but their independent activities of daily living are intact

mild neurocognitive disorder

-evidence of a modest cognitive decline in 1 or more cognitive domains based on:

1. concern of the individual, a knowledgeable informant, or the clinician

2. a modest impairment in cognitive performance, preferably documented by standardized neuropsychological testing

-the cognitive deficits do not interfere with capacity for independence in everyday activities

-synonymous with the term mild cognitive impairment

cortical dementia syndromes

deficits arising from brain damage that primarily affects the cerebral cortex

subcortical dementia syndromes

deficits arising from brain damage that primarily affects subcortical structures (e.g. basal ganglia, thalamus)

primary cortical pathology

Alzheimer’s disease, frontotemporal dementia

primary subcortical pathology

Parkinson’s disease, Huntington’s disease

primary cortical and subcortical pathology (mixed)

dementia with Lewy bodies, vascular dementia

AD signs

formation of amyloid plaques and tau tangles, cortical atrophy, neuron loss, synapse loss

amyloid cascade hypothesis

accumulation of amyloid plaques cause tau tangles, which affects brain structure, which affects memory, which affects clinical function

not the right disease model for all races/ethnicities

early-onset AD (EOAD)

-before 65

-5-10% of all AD cases

-sporadic or familial

-PSEN1, PSEN2, APP are deterministic genes that virtually guarantee that an individual will develop AD

late-onset AD (LOAD)

-after 65

-about 90% of all AD cases

-apolipoprotein E (APOE) is a risk gene for LOAD

APOE gene

-provides instructions for a protein called apolipoprotein E, which affects the pathogenesis of AD through multiple pathways, including the differential regulation of Aβ (key component of amyloid plaques) aggregation and clearance

-3 allelic variants: e2, e3, e4

-e4 variant has highest risk for Aβ aggregation and clearance; increases risk for Alzheimer’s disease and earlier onset

-e2 may provide some protection against the disease

-e3 plays a neutral role

signs of AD

• language production and comprehension

• prominent amnesia with rapid forgetting

• marked executive dysfunction

• visuospatial impairments

• processing speed

• a significant deficit in episodic memory is usually the earliest and most prominent manifestation of AD

early stage of AD (2-4 years)

• signs and symptoms often not recognized by friends and family

• repeatedly asking questions or making statements

• misplaces items

• gets lost easily

• word-finding problems

• personality changes (irritability, anger)

middle/moderate stage of AD (2-10 years)

• signs and symptoms usually obvious to family and others

• wandering, pacing, disruptive behaviors

• delusions (often paranoid) and hallucinations

• require supervision

• sleep cycles disturbed

• sun-downing and radical mood swings common

• require help with basic care activities

late/advanced stage of AD (last 1-3 years)

• little or no self care activities

• cannot speak or understand language

• bedbound, chair bound, unable to walk

• cannot recognize even closest relatives

• difficulty swallowing, pneumonia is common

• brain no longer can control body

AD treatment

symptomatic drugs

• address the cognitive and behavioral symptoms of AD

• do not stop or prevent disease

disease modifying drugs

• affect the underlying pathology

• designed to prevent onset or progression of AD

PD

• progressive neurodegenerative disorder that affects balance and motor control regions of the brain

• early onset before 50; late onset after 50 (more common)

• first symptom is often resting tremors

• starts on one side then becomes bilateral

PD pathology

• progressive neurodegenerative condition characterized by loss of dopaminergic neurons in basal ganglia and substantia nigra

• main pathology is alpha synucleinopathy (Lewy body)

PD motor symptoms

tremors, rigidity, postural instability, bradykinesia

PD non-motor symptoms

constipation, low BP, sexual dysfunction, urine incontinence, apathy, depression, visual hallucinations, drooling, dysphagia, fatigue/sleep problems, speech problems, masked facies

cognitive symptoms in PD

• visuospatial impairments

• memory profile: retrieval deficits

• marked executive dysfunction

• micrographia

• neuropsychiatric features: apathy, anxiety, depression

• dysphonia and dysphagia

AD memory deficit

encoding

PD memory deficit

retrieval

treatment of PD

• symptomatic in nature

• pharmacotherapy

  • dopaminergic drugs

• behavioral

  • speech therapy

  • occupational therapy

  • physical therapy

  • exercise programs

• surgical

  • deep brain stimulation

vascular cognitive impairment prevalence

hard to determine

• overlap with AD (34% of all dementia have vascular pathology)

• inconsistent criteria and cognitive findings

vascular dementia

• due to single or multiple infarcts

• white matter hyperintensities: chronic hypoperfusion and degeneration of white matter; small vessel disease

• related to hypertension and has other vascular risk factors

• associated with greater risk of stroke, cognitive impairment, progressive cognitive decline

• heterogeneous causes (many different causes)

• lack of pathologic diagnostic framework

• linked in time or anatomy to vascular disease

cognitive deficits in vascular dementia

• attention/processing speed impaired

• more severe executive dysfunction

• memory profile: retrieval deficits

• executive dysfunction is generally more severe than memory declines

limbic-predominant age-related TDP-43 encephalopathy (LATE)

• new

• can cause scarring of the hippocampus

• people diagnosed with AD may actually have LATE

• caused by a different type of tau

• need better in-vivo biomarkers

health inequality

differences in the health of individuals or groups; absent from the definition of health inequality is any moral judgement on whether observed differences are fair or just

health inequity/health disparity

-specific type of inequality that denotes an unjust difference in health

-health differences that are avoidable, unnecessary, and unjust

health inequalities are not all ____________

-health disparities

-ex: a higher rate of arm injuries among professional tennis players than in the general population

healthcare disparity

differences between social groups in health insurance coverage, access to and use of care, and quality of care

why are there disparities?

produced and sustained by deeply entrenched systems of power and structural drivers that are not based on what is morally right or fair

structural racism

-societies foster racial discrimination through mutually reinforcing systems of housing, education, employment, earnings, benefits, credit, media, health care, and criminal justice

-denial of structural racism a consequence of these systems

health equity

absence of unfair and avoidable or remediable differences in health among social groups

Heckler report on Black and minority health

• examined the health status of Americans by race/ethnicity and identified the gaps in disease rates, mortality, and other outcomes among Blacks compared to Whites

• helped lead to the creation of the NIH officed of minority health and health disparities

• found that Black people experienced about 60,000 excess deaths each year for people under 70

race

socially constructed way of grouping people, based on skin color and other apparent physical differences

ethnicity

• socially constructed way of grouping that emphasizes cultural commonalities

• Hispanic/Latinos is the largest minority group in the US

US census racial categories

white, black/African American, American Indian/Alaska native, Asian, native Hawaiian/other Pacific islander, some other race

which racial/ethnic group has the highest rate of dementia?

Hispanic

dementia prevalence vs race

• blacks and whites prevalence has decreased

• gap between blacks and whites has decreased

• Hispanic prevalence has been stable over time

• gap between Hispanics and whites increasing

Asian American AD

• less likely to have AD

• only 18% of Asian Americans are aware of MCI

  • harder for individuals or families to recognize symptoms and seek professional care

African American and Hispanic disparities in AD

• more likely to get AD, but less likely than whites to have a diagnosis

• typically diagnosed in later stages of the disease and therefore in need of more medical care (more expensive)

  • less likely to be included in clinical trials and have not been included in most AD research initiatives

why are African American and Hispanic older adults less likely to be diagnosed with AD and why aren’t they included in AD clinical trials?

• less likely to present for care

• less likely to have access to early/critical care initiatives

• clinicians may have a harder time diagnosing earlier stages of MCI/dementia

• neuropsychological measures are culturally based

• clinicians are not adequately trained or prepared to consider relevant cultural factors of influence

• perceptions of care and historical injustices

• discrimination

underlying pathology

different for racial/ethnic minority groups, likely because these groups are at increased risk for other detrimental health conditions (esp cardiovascular health conditions)

racial differences in mixed pathology

whites more AD while blacks more AD/LB

Hispanics smallest proportion of pure AD pathology

blacks and Hispanics greater proportions of cardiovascular disease and AD + CVD

racial/ethnic disparities in AD summary

• racial/ethnic minority groups are at increased risk for AD

• likely the consequence of social disadvantage and other disparities

• seem to be general differences but needs to be further explored

• manifestation of AD (prevalence of amyloid/tau) differs across groups (relevant to treatments)

racial/ethnic disparities in neural imaging

black and Hispanic AD caused more by sociodemographic factors and mixed pathology

white AD caused more by amyloid and APOE e4

WEIRD problem in science

western, educated, industrialized, rich, democratic

inclusion in clinical trials

minority groups make up about 39% of the US population but are under enrolled in clinical trials

largest minority in US

Latinos

sex assigned at birth

sex assignment by doctors that is usually based on genitals

gender identity

internal experience and understanding of our own gender

gender expression

the way in which we present ourselves, which can include physical appearance, clothing, or behaviors

sexual orientation

different forms of attraction; can be attracted to one gender, multiple genders, or different genders throughout your life

sexual minority

encompasses lesbian, gay, two-spirited, bisexual, and queer identifying populations

gender minority

umbrella term for transgender and non-binary people whose gender identity/expression does not conform to social expectations based on their sex assigned at birth

issue 1 for SAGM

LGBT older adults are more likely to age without a spouse or partner, more likely to live alone, and less likely to have children to support them

issue 2 for SAGM

LGBT older adults have a greater number of chronic diseases (HIV/AIDS, diabetes, cardiovascular disease) when compared to their non-LGBT peers, and LGBT elders of color face greater health disparities than their white LGBT counterparts (many of these health conditions have been linked to an increased risk of AD and VD)

issue 3 for SAGM

these disparities mean that this population needs supportive services, but many LGBT elders experience barriers to accessing help, including discrimination, heterosexist attitudes, and a lack of cultural competence on the part of providers

rainbows of aging preliminary findings

• at increased risk for dementia due to health disparities

• higher levels of subjective cognitive complaints

• underserved within our healthcare system

• face unique financial and social caregiving barriers

• less likely to seek out medical care

SAGM study 1

• examined ICD-9 diagnostic codes in electronic health records

• trans people more likely to be on disability

• trans people experience multiple chronic conditions at higher rates than CMBs

SAGM studies 2 and 3

• 8% LGB vs 9% heterosexual were diagnosed with dementia

  • 8% opposite-sex vs 12% same-sex were diagnosed with dementia (not statistically significant)

bias

systematic error in an epidemiologic study that results in an incorrect estimate of the association between exposure and the health outcome

sources of bias

data source, data collection, sexual/gender identity categorizations within the study, disclosure of relevant information, ICD-10 codes, and how dementia was diagnosed

selection bias

occurs when the subjects studied are not representative of the target population about which conclusions are to be drawn (study 2 (Kaiser Permanente study) was predominantly white, educated, middle-class older adults)

measurement bias

is a distortion in the measurement of an association that is caused by inaccurate measurements of key study variables (how we measure who is and isn’t LGBT (ICD-10 codes), as well as who does and does not have dementia impacts our observation of an association)

SAGM study 4

• significantly higher rates of subjective cognitive decline in 16% LGBTQ+ group vs 11% non-LGBTQ+

  • highest in bisexuals, then trans people, then lesbians, then gays

HIV associated neurocognitive disorder (HAND)

• clinical diagnostic criteria differs from other neurological disorders/dementias

• neurocognitive profile indicates impairments across multiple cognitive domains

• executive dysfunction is more common than memory problems

• can be diagnosed at any point in time

HAND/HAD are analogous to __________

• HAND analogous to MCI (mild neurocognitive disorder)

• HAD (HIV associated dementia) analogous to major neurocognitive disorder

HAND/HAD

• not amyloid or tau causing problems but poor immune functioning has negative effects on the brain

• Nadir CD4 count is best predictor of whether someone will have HAND (lower than healthy adults)

• when you have a low CD4 count, you have an increased risk for opportunistic infections

• rates of HAND/HAD have decreased since antiretroviral therapy and are on the decline with PrEP

ADRD in SAGM summary

• research on understanding cognitive aging, brain health, and dementia risk in LGBTQ+ members started very recently

• large retrospective epidemiological studies of dementia prevalence have been mixed and may be subject to bias

• LGBTQ+ have more subjective cognitive complaints and demonstrate health disparities (chronic disease burden, HIV) that place them at risk for dementia

• stigma, caregiving, and income factors are also necessary points of consideration for management of dementia

IOM report conclusions

1. sex is an important human variable that should be considered in health-related research, as there are sex differences in health and illness

2. the study of sex differences needs to move beyond descriptions into a mature science that explores biological mechanisms

3. there have been profound barriers to the advancement of knowledge about sex differences that must be eliminated

sex differences

• differences in immune function

• differences in symptoms, type, and onset of cardiovascular disease

• differences in response to toxins

• differences in brain organization

• differences in pain

sex differences in AD risk

increased in women but most likely due to the fact that women live longer than men on average