DEMENTIA Disclaimer Speakers Bureau Pfizer Eli Lilly Janssen - - PowerPoint PPT Presentation

DEMENTIA

Disclaimer

Speaker’s Bureau

• Pfizer
• Eli Lilly
• Janssen
• Sunovion

“Fun” facts about Dementia before we start

u AD is 6th Leading cause of death in the US; 5th for those 65

and older

u Women make up a larger share (2/3) of Alzheimer’s (AD)

patients than men

u Lifetime risk is 20% for women and 10% for men at age 45 u AA and Hispanics are morel likely to have AD as likely as

• Whites. LOWEST FOR ASIAN-AMERICANS! The Japanese

have the lowest.

u Negative socio-economic characteristics maybe increase

for those groups

More “fun” facts

u In the US, 15.8% of age 60 and older have MCI u The oldest member of the Baby Boom generation (1946-

1964) just turned 72 in 2018

u Decline in the age-specific risk of AD and other dementias

in the past 25 years

u BUT a dramatic increase is expected in the TOTAL NUMBER

• f cases

u A worldwide trend showing an increase in OBESITY and

DIABETES can potentially reverse the declining trend

u In low- and middle-income countries, such as the

Philippines, there is no evidence that the risk for AD and

• ther dementias has been declining

Last “fun” facts

u$232 Billion expense in 2017 and $277

Billion in2018

uCosts extend to family caregivers’

increased risk for emotional distress and negative mental and physical health

• utcomes

uWith the identification of biomarkers in

recent years, our understanding of AD has changed

NEURO-COGNITIVE DISORDERS (NCD)

Acquired and represents decline from previous level of functioning

Mild NCD aka Mild Cognitive Impairment (MCI or MCD)

u Moderate decline u Modest impairment u Does not interfere with

independence

u +/- Behavioral Disturbance

Moderate NCD aka DEMENTIA

u Significant decline u Substantial impairment u 2 or more cognitive domains

u

Attention, Learning/Executive Function, Memory, Language, Emotion, Visuospatial Function/Motor & Action

u Interferes with independence u +/- Behavioral Disturbance u Mild, Moderate or Severe

Possible Reversible Causes of NCD

u Depression u Delirium u Substance or Medication Induced

> Alcohol > Medication Mismanagement > Anticholinergics > Benzodiazepines

BENADRYL, Parkinson’s Rx, Antipsychotics, Ditropan > Ativan, Xanax, Clonazepam, Vaiium

> Statins > Medication Mismanagement

u Hypothyroidism, Vit B12 Deficiency, Neuro-syphillis u Normal Pressure Hydrocephalus (NPH), Subdural Hematoma, Brain Tumor u Sensory Impairment, especially hearing

DEPRESSION

u Associated with an increased risk of Alzheimer’s Disease u Depression and other neuropsychiatric symptoms often

emerge during the preclinical phase of AD – a period marked by the accumulation of deposits of fibrillar amyloid and pathological tau

u Cognitively normal older adults with worsening anxiety

had higher levels of amyloid beta, a brain protein implicated in AD

LINK BETWEEN DEPRESSION AND DEMENTIA

u Those with MCI were 2.6 times more likely to

have a history of depression

u Those with AD were 3.77 times more likely to

have had depression

DEPRESSION WITH ANXIETY

uWhen compared with other symptoms

• f depression, ANXIETY SYMPTOMS

increased over time in those with higher amyloid beta levels in the brain

uAnxiety may be a manifestation of the

disease process BUT it may also be a DISEASE-POTENTIATING FACTOR

ANTI-DEPRESSANT MEDICATION

uThe antidepressant SSRI Citalopram and

Sertraline decrease amyloid-Beta generation and plaque load.

uSSRI was associated with delayed dementia

• nset and increased longevity in patients

with Down Syndrome, who have a high risk

• f AD

ANTI-DEPRESSANT MEDICATIONS

u Long-term treatment of depression (more than 4

years, even after the depressive symptoms have resolved) with SSRI of those with MCI was associated with a delay of approximately 3 years in progression of Alzheimer’s

u SSRI cannot stop the AD pathology u Non-SSRI antidepressants were associated with a

higher risk of progression from MCI to AD

DELIRIUM (vs Dementia)

u Disturbance in ATTENTION or AWARENESS + another deficit u Develops over short period of time and tends to fluctuate u Direct physiological consequence of something else u Hyperactive (easy to Dx) or hypoactive (easy to miss)

types

u Can be reversible – SIGNIFICANT CAUSE OF MORBIDITY AND

MORTALITY during acute hospital admission

SENSORY IMPAIRMENT- HEARING LOSS

u Age-related hearing loss linked to impaired performance

across cognitive domains and increased risk for Dementia diagnosis

u Underlying PSYCHOSOCIAL MECHANISM of diminished

hearing leading to increased risk for depression

SENSORY IMPAIRMENT – HEARING LOSS

u Underlying NEUROBIOLOGICAL MECHANISM of diminished

hearing leading to increased risk for depression

u DECREASE COGNITIVE PERFORMANCE and INCREASE

DEPRESSION RISK by

uReducing cognitive reserve uIncreasing executive dysfunction uDisrupting normative emotion reactivity and regulation

What does it mean to have “Dementia?”

u COGNITIVE IMPAIRMENT u Learning and Memory u Executive Function u Language Skills u ETC u FUNCTIONAL IMPAIRMENT u Instrumental Activities of Daily Living (IADLs) u Activities of Daily Living (ADL)

Diagnosis of Dementia

uIs cognitive impairment present uIs there anything I can fix? uTime will tell – Is this dementia? If

so, what is the etiology?

Basic Work-Up for Dementia

u Clinical Evaluation u Hx – Cognitive & Functional (collaborative informant) u Cognitive Testing – MMSE or Montreal Cognitive

Assessment

u Neurological Exam – Focal S/Sx, Parkinsonism u Review of Current Rx and Substance Use u Laboratory Studies (TSH, B12, Syphillis) u Brain Imaging – CT Scan or MRI, possibly PET Scan u Others as clinically indicated – Lyme’s, EEG

Dementia in the Elderly

u Alzheimer’s Disease

65%

u Frontotemporal Lobar Degeneration

10%

u Vascular Dementia

10%

u Lewy Body Dementia

5%

u Other/Mixed

10%

u Substance/Medication Use, HIV Infection, Prior Disease, Parkinson’s

Disease, Huntington’s Disease, Other Medical Conditions

u

These numbers vary widely

ALZHEIMER’S DISEASE

u Primary deficit is the decline in memory and learning – short-

term, episodic

u Executive Dysfunction can occur early on u Insidious onset and gradually progressive decline u Cause is multifactorial; <5% is genetic; plaques and tangles in

the brain

u Greatest risk factor is advancing age; also family history and

genetics (ApoE3 allele)

u Neurological exam unremarkable in mild to moderate stages u AD is a LIFE-LIMITING ILLNESS that lasts 8-12 years on average

ALZHEIMER’S DISEASE

u Cognitive Impairment u Amnesia (partial or total loss of memory) u Aphasia (loss of ability to understand or express

speech)

u Apraxia (inability to perform purposeful actions) u Agnosia (inability to interpret sensations and to

recognize things)

u Executive Dysfunction u No evidence of neurological disease, metabolic etiology,

substance-induced, or delirium

u Significant functional impairment in IADLs or ADLs

Early Stage of AD - Mild

u Short-term memory is poor u Expressive language and naming are affected u Executive function is impaired u Trouble with IADLs (higher level activities) u Some activities are taken over by others u Need gentle reminders and supervision u Close family and friends can notice

What does early AD typically look like?

COGNITIVELY

u Short-term memory loss u Word-finding difficulties u Trouble with reasoning u Becoming lost or

disoriented FUNCTIONALLY

u Forget conversations u Forget dates, miss

appointments

u Misplace items frequently u Trouble with finances u Get lost while driving

Stages of AD – Moderate (Middle)

u Long-term memory becomes affected u Decision-making is harder (limit to 2 choices) u Speech comprehension is difficult u “Praxis” (doing things) is more impaired u ADLs are affected (personal care) u Need cuing, set-up and assistance u Incontinence develops in the 2nd half u Gait disturbance with falls u Becomes more obvious to others

Stages of AD – Severe (Late)

u All cognitive domains are affected u “Gnosis” (recognizing people) is affected u Very basic information is lost, including one’s name u Become unable to walk, talk, feed oneself u Fully dependent on others for care u Neurological changes and abnormalities u Swallowing becomes affected

FRONTO-TEMPORAL DEMENTIA (FTD)

u Age of onset: 40-65 u Behavioral variant – Pick’s Disease (Frontal Lobe) u Language variant – Primary Progressive Aphasia or

Semantic Dementia (Temporal Lobe)

u Relative sparing of learning, memory, and perceptual

motor function

u Several different gene mutations have been identified u Most cases without family history u Can be associated with Motor Neuron Disease (ALS)

VASCULAR DEMENTIA

u Presence of sufficient cerebrovascular disease u Prominent deficits in complex attention and frontal

executive function

u Symptoms vary u Thinking is more affected than memory u Temporally related to cerebrovascular events u Can occur suddenly (pot-stroke) or step-wise (series of

strokes)

u Exam may show focal deficits and gait disturbance u Risk Factors: Age, Hx of MI, CVA, TIA, Atherosclerosis,

Hyperlipidemia, HTN, DM, Smoking, A-fib

DEMENTIA WITH LEWY BODIES

u Prominent visual hallucinations u Fluctuation in attention and awareness – mimics

delirium

u Subsequent Parkinsonism (slowed movement,

rigidity, imbalance with falls)

u REM Sleep behavior disorder and neuroleptic

sensitivity are common

u Risk factors: Age, Male, family history of DLB

DEMENTIA DUE TO TRAUMATIC BRAIN INJURY

TBI increases risk of developing AD, PD, or Dementia Pugilistica (Boxers)

u External force to the head or body (mild, moderate,

severe)

u Causes are falls, motor vehicle collisions, violence, sports

injuries, blasts

u LOC, post-traumatic amnesia, disorientation & confusion,

neurological signs

u NCD presents IMMEDIATELY after and persists u Affects attention, speed of processing, memory, executive

function

PARKINSON’S DISEASE WITH DEMENTIA

u Must have an established diagnosis of PD u Cognitive dysfunction is very common u Dementia occurs in 20-40% of PD late in the

disease (10-15 years)

u Slowed thinking, impaired

attention/concentration, executive dysfunction

u Risk Factors: Age, More severe motor symptoms

PLAN OF CARE FOR DEMENTIA #1 Address Safety Issues

u DRIVING!!! u The ability to drive safely is lost at this stage u Guns u Medications u Finances u Cooking u Wandering u Falls

PLAN OF CARE FOR DEMENTIA #2 General Management

u Manage neuropsychiatric comorbidities u Control vascular risk factors u Discontinue offending medications u Increase hydration u Physical exercise u Cognitive stimulation u Social engagement u Memory aids (pillbox, calendar, etc.) u Advance planning = Home Care Assistance

PLAN OF CARE FOR DEMENTIA #3 Dementia Specific Medications

u Symptomatic Treatment – not disease modifying u Modest and temporary response u Cholinesterase inhibitors (ChEi) u Donepezil, Rivastigmine, Galantamine – no significant

difference between them

u For mild, moderate or severe stages of AD u S/E: N/V/D and weight loss (less with patch),

bradycardia, syncope, falls, urinary frequency

PLAN OF CARE FOR DEMENTIA #3 Dementia Specific Medications

u NMDA Receptor Antagonist u Memantine u For moderate to severe AD u Comes in XR (24 hour capsule can be sprinkled) u Reduce the dose with severe renal impairment u S/E: Dizziness,irritability u Evidence for combination therapy u Namzaric

POTENTIAL PHARMACOLOGICAL TREATMENTS

u Targeting amyloid beta u Breaking up the amyloid beta by binding them to prevent amyloid

aggregation

u Blocking the enzyme Beta-secretase (BACE) that produces amyloid

beta

u Vaccination to induce the immune system to generate the antibodies

against the amyloid beta

u Targeting the Tau u Inhibition of the Receptor for Advanced Glycation End Products (RAGE)

that may interfere with inflammation and amyloid transportation into the brain

POTENTIAL PHARMACOLOGICAL TREATMENTS

u A molecule that hits several types of Serotonin, Dopamine

and Glutamate receptors is being developed for the treatment of agitation in AD and other dementia, as well as Schizophrenia

u Other strategies being research to treat AD include fixing

dysfunctions in

u Mitochondria (produce energy for cells) u Endocytosis (transportation of molecules in and out of

cells)

u Autophagy (self-cleaning process inside cells)

NEW TOOLS BEING DEVELOPED

u Sharpen the brain images u Cutting-edge biomarkers (PET Imaging or

molecules in CSF) to help diagnose AD early and measure disease progress with unprecedented accuracy

u Refinement in genetic analysis may clarify

different pathological processes in subgroups of AD and lead to more targeted treatment

BEHAVIORAL AND PSYCHOLOGICL SYMPTOMS OF DEMENTIA (BPSD)

u Behavioral symptoms: loud vocalization, restlessness,

agitation, wandering, physical aggression (not the norm)

u Psychological symptoms: anxiety, depressive mood,

hallucinations, delusions

u Usually in the Middle to Late stages u Apathy is prevalent throughout u Sleep disorders are common (Circadian Rhythm

Disturbance)

u Can negatively affect the quality of life

BPSD NON-PHARM MANAGEMENT

u Rule-out medical causes u Pain, constipation, delirium from illness u Establish other root causes u Boredom, routine change, personal needs, fatigue,

environmental factors, mismatch of task & ability, arguing

u Use behavioral interventions u Individualized approaches directed toward

understanding, preventing, relieving, and/or accommodating distress or loss of abilities

BPSD PHARMACOLOGIC MANAGEMENT

There is no FDA-approved treatment for BPSD

u Choose a target behavior, for example u Depression or anxiety – SSRI u Psychosis or fearfulness – Antipsychotic u Sleep disturbance – Sedating antidepressants u Situation agitation/aggression – Low-dose BZD u Persistent aggression – Antipsychotic or Mood Stabilizer u Consider the frequency & severity u RULE OF THUMB: START WITH ½ OF THE SMALLEST PILL

Key Principles for Antipsychotic Use

u Ideally, for dangerousness, psychosis or mania u Antipsychotics only when non-pharm has failed u Document the reason & rationale for starting u Time-limited use with gradual dose reductions u Inappropriate for vocalizations and wandering

BPSD PHARMACOLOGIC MANAGEMENT

u Small improvements in certain symptoms with

Antipsychotics

u Other evidence in favor of Risperidone u Choice is largely based on side-effects profile u Citalopram may be as effective as Risperidone uTry an SSRI before an antipsychotic, if

appropriate

PREVENTION & INTERVENTION

u Conceptualizing cognitive impairment as a GERIATRIC SYNDROME

rather than a set of clinical or preclinical diagnoses

u Evaluation and management of cognitive decline should include u Assessment ad treatment of depression u Screening for hearing impairment u Appropriate referral u

Other components to be incorporated should address cerebrovascular risk factors, especially white matter disease, such as management of

u HTN u DM u A-fib

PREVENTION & INTERVENTION

u Active treatment of midlife obesity u Exercise u Dietary modifications u Mediterranean diet with low proinflammatory potential u Smoking cessation u Assessment of alcohol intake, with MODERATION being the focus in

midlife and CESSATION being important if cognitive impairment is present in later life

u Social engagement prevents loneliness and depression u Participation in cognitive stimulating leisure activities is associated

with higher cognitive performance

u Attending to mobility issues as impairments have been shown to

worsen outcomes for a variety of disorders and are associated with cognitive decline

About 35% of Dementia is attributable to 9 MODIFIABLE FACTORS occurring across the lifespan:

u Education to a maximum of age 11-12 years u Midlife HTN u Midlife Obesity u Hearing loss u Late-life depression u Diabetes u Physical Inactivity u Smoking u Social Isolation

DISCLOSURE OF THE DIAGNOSIS

u What you say versus what they hear u Most patient and families prefer PROGRESSIVE

DISCLOSURE

u 1st Visit – Investigate (“I am concerned about your

memory/thinking)

u 2nd Visit – Review the findings and provide a plan of

care

u Subsequent Visit – Provide a working diagnosis

u Concept of therapeutic privilege, i.e. do no harm