Alzheimer's and Dementia

Definition and Epidemiology of Dementia

• Dementia is a generalized decline in cognitive functioning that impairs the ability to perform activities of daily living.
• Alzheimer's disease (AD) is the most common cause of dementia, affecting 5-13% of people over 65 and 30% of those over 85.
• By 2050, an estimated 12.7 million older adults over 65 will have AD.
• AD is the fifth leading cause of death in the United States among this age group.
• Up to 50% of nursing home residents have AD or another form of dementia.
• Early detection is crucial for managing risk factors, symptoms, and providing support for patients and families.
• Dementia includes progressive cognitive decline and behavioral changes that interfere with independence.
• The DSM-5 classifies dementia as Major Neurocognitive Disorder with various underlying etiologies, including AD, frontotemporal lobar degeneration, Lewy body disease, vascular disease, traumatic brain injury, substance/medication use, HIV infection, prion diseases, Parkinson's disease, Huntington's disease, other medical conditions, multiple etiologies, or unspecified causes.
• AD accounts for up to 80% of dementia cases.
• Approximately half of individuals over 80 with AD pathology also have other pathologies like vascular disease or Lewy body disease.

Mild Cognitive Impairment (MCI)

• MCI is a clinical label that represents mild cognitive decline due to a range of possible underlying etiologies.
• MCI is considered a transitional phase that ends with dementia, when a neurodegenerative disease process is believed to be the underlying cause of cognitive difficulties.
• 20-40% of individuals with MCI progress to dementia at a rate of 10-15% per year.
• MCI is a risk factor for all types of dementia, requiring close monitoring and follow-up.
• Diagnosis of MCI requires a change in cognitive abilities, gathered through interviews with the patient and a knowledgeable collateral source, when possible.
• Objective cognitive impairment is assessed via neuropsychological examination, evaluating memory, language, attention, executive functions, and visuospatial abilities.
• Impairment in one or more cognitive domains, along with preserved ability to maintain functional independence, is required for MCI diagnosis.
• Mild problems in instrumental activities of daily living (e.g., managing finances) may be observed.
• MCI is classified into four subtypes: amnestic MCI (aMCI) single domain, aMCI multiple domain, nonamnestic MCI (naMCI) single domain, and naMCI multiple domain.
• aMCI indicates memory impairment, while naMCI indicates impairment in other cognitive domains.
• Deficits may be restricted to one cognitive domain (MCI single domain) or multiple cognitive domains (MCI multiple domains).
• Neuropsychological assessment distinguishes between MCI and dementia, using age- and education-appropriate normative data.
• Dementia and MCI must be distinguished from age-related cognitive decline, which does not lead to functional impairment.
• Early detection and characterization of cognitive changes are important for early intervention and treatment planning.

Pathophysiology and Clinical Presentation of Alzheimer's Disease (AD)

• Greater than 95% of AD cases are idiopathic and occur over the age of 65 (“late onset”).
• "Early onset" AD presents before age 65 in approximately 5% of cases.
• Early-onset AD is usually idiopathic, but in approximately 1% of total AD cases (11% of early onset cases) is associated with a genetic mutation (i.e., amyloid precursor protein, presenilin 1, or presenilin 2
• Apolipoprotein E4 (ApoE4) increases risk of late-onset AD.
• Approximately 25% of people carry one ApoE4 allele, increasing risk 4 times, and 2-3% carry two alleles, increasing risk 14 times, compared to the neutral ApoE3/3.
• In AD, cortical atrophy occurs due to extracellular β-amyloid plaques and intracellular tau protein tangles.
• Cortical atrophy initially impacts the hippocampus, causing early memory issues, and progresses along a temporal–parietal–frontal trajectory.
• Biochemically, there is disruption to the cortical pathways involved in catecholaminergic, serotonergic, and cholinergic transmission.
• AD is divided into early, middle, and late stages.
• The initial AD symptom is memory loss for recent events.
• Other early-stage symptoms include difficulties with word-finding and planning/organizing activities.
• The middle stage, the longest, involves worsening memory, impairments in other cognitive areas, mood changes, psychiatric symptoms, disorientation, sleep problems, and trouble with dressing/continence.
• The final stage includes complete loss of independence, severe cognitive impairment, loss of awareness, motor/communication difficulties, and vulnerability to infections.
• The average disease duration from diagnosis to death is 9 years, varying from 4 to 20 years.
• Staging helps patients and families plan care and treatment.

Vascular Mild Cognitive Impairment/Dementia

• Ischemic and/or hemorrhagic cerebrovascular disease (CVD) is a common cause of MCI and dementia.
• CVD accounts for approximately 17% of dementia cases, often alongside AD pathology in over 75% of cases.
• Individuals with hypertension, diabetes, hyperlipidemia, or peripheral vascular occlusive disease are at higher risk.
• Vascular MCI/dementia should be related to a vascular event and/or show enough CVD evidence on imaging to explain cognitive impairment.
• Cognitive symptoms include difficulties in attention, processing speed, and executive functioning.

Dementia With Lewy Bodies (DLB)

• DLB and Parkinson disease dementia (PDD) are considered a spectrum of Lewy body disease (LBD).
• LBD is commonly the second leading cause of dementia after AD.
• DLB includes fluctuating alertness, visual hallucinations, REM sleep behavioral disorder, and parkinsonism features.
• DLB is diagnosed when dementia occurs before or concurrently with parkinsonism.
• PDD is diagnosed when dementia occurs after well-established PD.
• Patients with DLB are sensitive to neuroleptics like haloperidol and may develop neuroleptic malignant syndrome.
• Neuroleptics should be avoided when treating hallucinations in LBD.
• Survival is estimated at approximately 7 years after dementia onset.

Other Dementias

• Many other movement disorders and neurodegenerative diseases can present with cognitive symptoms and dementia.
• These includes frontotemporal dementia (FTD), primary progressive aphasia (PPA), posterior cortical atrophy (PCA); and other disease processes HIV-associated neurocognitive disorder, idiopathic normal-pressure hydrocephalus
• Behavioral/personality changes before age 65 warrant evaluation for FTD or rare AD variants.
• Early language challenges may indicate PPA.
• Visuospatial difficulties may indicate PCA or other dementias.

Clinical Assessment of Dementia

• Common symptoms include memory loss, personality changes, language disturbances, and challenges with independence.
• Family members or friends typically initiate evaluation.
• Subtle cognitive changes may be overlooked or attributed to old age.
• Individuals with dementia may have reduced insight into their condition.
• Some individuals may be concerned about self-perceived decline in cognitive functioning in the absence of objective cognitive impairment on neuropsychological assessment.
• Evaluation includes interviews with the patient and family, a physical and neurologic examination.
• Neuropsychological evaluation provides comprehensive, objective cognitive assessment.
• The neuropsychologist can identify cognitive strengths and weaknesses and inform the patient of the most likely underlying etiology of impairment.
• Thorough medication review is important, including anticholinergic drugs.
• Physical examination focuses on neurologic signs, blood pressure, and carotid bruits.
• Monitor for changes in cognition, mood, and behavior (anxiety, restlessness, aggression, delusions, hallucinations, wandering).
• Brief screening measures (Katz Index, Get Up and Go test, MMSE, Mini-Cog, MoCA, MIS, GDS, PHQ-9) can estimate cognitive impairment, mood, and independence.
• Screening tools are brief and low-cost, tracking yearly score change.
• Instruments lack diagnostic precision and results can be impacted by education, literacy, knowledge of english etc
• Can be limited by ceiling effects.
• Supplement screening with informant/caregiver questionnaires or interviews.
• Determine which individuals would benefit from more extensive neuropsychological assessment.

Diagnostics for Dementia

• Determine if the patient has a reversible condition causing cognitive decline.
• Important tests include CBC, TSH, vitamin B12 and folate levels, and metabolic screen.
• Measure medications with measurable levels (digoxin, carbamazepine, theophylline, divalproex sodium).
• Research focuses on refining biomarkers (amyloid/tau/FDG-PET, SPECT, CSF analysis).
• Referral to a dementia specialty program or neurologist is often required for additional workup.
• Baseline brain imaging is recommended to identify atrophy patterns, lesions, or infections.
• Non-contrast CT is generally adequate, but MRI offers better resolution.
• PET and SPECT may be useful in difficult cases and should be discussed with a neurologist.
• Amyloid PET scans can help diagnose AD, but insurance coverage is not guaranteed.
• Cognitive changes have innumerable causes that cannot always be easily determined.
• Consider delirium/encephalopathy and pseudodementia as differentials.
• Gather details about the evolution of cognitive changes.

Delirium

• Delirium is a reversible differential diagnosis to consider when assessing an older adult for possible dementia.
• Delirium represents represents an acute change in mental status, which can develop from a general medical condition, substance intoxication or withdrawal, medications, or multiple etiologies.
• In older adults, delirium is often the first and only indicator of underlying physical illness.
• Delirium is characterized by a disturbance in attention, consciousness, and cognition.
• Increasing delirium duration is associated with long-term cognitive impairment.
• Delirium is the leading complication of hospitalization in older adults.
• Many patients who become delirious are never recognized as such and may be incorrectly labeled as having dementia or a psychiatric disorder.
• Patients with an underlying dementia are at even greater risk of developing delirium in the setting of acute illness, which is known as delirium superimposed on dementia.

Pseudodementia

• Depression itself can impact cognition, which is referred to as pseudodementia.
• Depression and dementia have overlapping symptoms.
• Cognitive symptoms often persist as residual symptoms in patients for whom depression has remitted.
• Cognitive difficulties that coincide with the onset of a major depressive episode in the context of previously normal cognition may be more likely due to the depression.
• In older adults, depression increases risk for dementia.
• Carefully follow older adults with depression, even after remission.

Interprofessional Collaborative Management of Dementia

• Management depends on the stage of disease.
• Goal includes treatment of correctable factors to improve daily functioning and foster functional independence.
• Encourage physical/mental health, cognitive/social engagement, exercise, healthy diet (Mediterranean), and good sleep.
• Address safety concerns, including driving.
• Kitchen safety and home environment evaluations are important.
• Recommend consultation with an attorney for future legal and health matters.
• Discuss patient preferences for resuscitation and medical devices.

Pharmacologic Management of Dementia

• Three FDA-approved drug classes treat cognitive symptoms of AD: cholinesterase inhibitors, NMDA receptor antagonists, and aducanumab.
• Aducanumab (Aduhelm) is a disease-modifying therapy targeting amyloid β, but its efficacy is controversial.
• Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) prevent acetylcholine breakdown.
• Used for mild dementia due to AD and may improve cognitive symptoms in LBD.
• The choice between these medications is based on cost, mode of delivery (patch vs. pill vs. liquid), and individual patient tolerance.
• Memantine (Namenda) is an NMDA receptor antagonist regulating glutamate, used alone or with cholinesterase inhibitors for moderate disease and beyond.
• Namzeric is a combined cholinesterase inhibitor and glutamate regulator.
• These medications may delay symptom worsening and improve functional status but do not alter the course of dementia.
• Treat and manage vascular dementia risk factors (hypertension, hyperglycemia, smoking, hyperlipidemia, diet).
• SSRIs are used for mood symptoms such as depression, anxiety etc
• Sertraline and citalopram improve neuropsychiatric symptoms and are because of their wide therapeutic range.
• Mirtazapine and trazodone can also be useful when sleep disturbance is present.
• Cognitive-behavioral therapy (CBT) aims to change negative thinking patterns with the understanding that thoughts, behaviors, and feelings are interconnected.

Mood and Behavioral Symptoms Management

• Identify reversible causes of symptoms (infection, pain, constipation, hypoxia).
• Consider environmental changes and medications (benzodiazepines, anticholinergics).
• Educate family members and caregivers about managing difficult situations.
• Medications for behavior management should only be used when nonpharmacologic interventions have failed and there is a need to protect the patient, caregivers, or both.
• Avoid antipsychotics unless patients are at risk of harm; consider referral to psychiatry.
• Discuss risks/benefits of antipsychotics with patients and caregivers; use the lowest effective dose for the shortest duration.
• Benzodiazepines and opioids are both associated with cognitive dysfunction.
• Long-term benzodiazepine (not opioid) use increases risk of dementia and should be avoided.
• Caution patients regarding the use of over-the-counter preparations.

Indications for Referral or Hospitalization

• Involvement of other disciplines is helpful for patients, families, and providers.
• Physical therapists can optimize function.
• Occupational therapists perform driving evaluations and functional assessments.
• Speech therapists may be consulted for dysphagia assessments.
• Referrals to neurology and neuropsychology are helpful to differentiate unusual or unclear presentations of dementia.
• Patients with end-stage dementia are eligible for referral to hospice.

Complications of Dementia

• Complications vary with the stages of illness.
• Early stages: safety risks (getting lost, motor vehicle accidents, leaving stove on, mismanaging medications/finances, scams).
• Middle stage: falls, incontinence, and sleep disturbances.
• Late/final stages: contractures, pressure sores, urinary tract infections, and pneumonia.
• Deconditioning and nutritional deficits are also common.
• Apraxia may develop, requiring help with basic functions.
• Weight loss is inevitable, and death is often due to infectious complications.

Patient and Family Education and Health Promotion

• Maintain independence by emphasizing strengths and allowing normal activities, being mindful of safety.
• A person who is no longer able to follow a recipe may still be able to knead dough and make a loaf of their special bread with help.
• A grandparent unable to be left alone with their grandchild is still able to rock an infant to sleep and sing a lullaby that they once heard as a child.
• A carpenter may no longer be able to operate eletrical shop tools but may still be able to hammer and glue pieces of furniture that have been precut.
• Feeling robbed of self-esteem is a major detriment to function—and education for families is essential.
• Provide behavioral guidance, books, social support, and recognition of the difficult caregiver role.
• Guide families regarding appropriate settings and activities.
• Discuss the decision about placement in a nursing facility.
• Families need to be educated about delirium and possible behavioral changes.
• Provide resources and information about support groups, financial/legal matters, and how to communicate the diagnosis.
• Encourage families to contact the local Alzheimer’s Association chapter and to explore clinical trial participation.