Dementia

1. Dementia Sanjay K Nigam, M.D. Psychiatry Director, Greenville Regional Hospital

2. History • Careful and accurate history • Distinguishing exceptional symptoms from complaints due to age-related cognitive decline • Assess the patient for depression, and inquire about behavioral and psychotic disturbances • Consider conditions whose symptoms and signs mimic those of neurodegenerative dementia • Obtain and review the patient's medication history for drugs

3. Testing • Office and Laboratory • Radiologic • Invasive • Differential Diagnosis • Rule out conditions or disorders that may mimic a neurodegenerative dementia

4. History • careful and accurate history • onset and course of memory and thinking problems • informed collateral source (generally a spouse or adult child) • patient's cognitive performance or behavior that negatively affect his/her daily life • temporal course of symptoms • chronic, stepwise, or progressive • patient's recent and long-term memory • everyday activities • driving, functioning at work, and/or interactions with family and peers • functional loss is not due to physical decline (vision or hearing loss)

5. History (cont…) • Distinguish exceptional symptoms • from complaints due to age-related cognitive decline • Cognitive changes due to usual aging • limited attentional resources ("I forgot what I came in here to get") • or to diminished speed of information processing ("I couldn't remember his name until later"). • Such changes usually do not progress nor do they seriously interfere with everyday activities. • Assess the patient for depression, and inquire about behavioral and psychotic disturbances • patients with depressive "pseudodementia“ • acute onset • past episodes of depression, anhedonia • memory deficits that are equal for recent and remote events (vs. greater for recent events in AD), • circumscribed (vs. global) cognitive defects • Patients with mild to moderate AD have memory and other cognitive disturbances, but do not have the prominent delusions and gross perceptual distortions that are characteristic of psychotic disorders • conditions whose symptoms and signs mimic those of neurodegenerative dementia • Ask about other medical problems that might complicate the patient's evaluation or management • patient's medication history for drugs • drugs that may cause or exacerbate loss of mental capacity, especially • opiates, sedative-hypnotics, analgesics, • anticholinergics, anticonvulsants, corticosteroids, • centrally acting hypertensives, psychotropics, alcohol.

6. Physical Examination • for possible coexisting abnormalities • Focus on focal deficits, extrapyramidal signs, and gait disturbances • dry skin, periorbital edema, thin hair, and depressed reflexes may indicate hypothyroidism; • extrapyramidal signs may indicate Parkinson's disease or dementia with Lewy bodies • focal motor or sensory deficits may indicate vascular dementia • gait disturbances may indicate communicating hydrocephalus • Coexisting conditions that may exacerbate dementia include profound hearing or visual loss that isolates the patient • In more advanced stages of AD, neurologic examination often reveals motor dysfunction and reflex abnormalities

7. Testing • standardized mental status tests • urinalysis, • neuroimaging, • complete blood count, • blood chemistry battery • electrolytes, glucose, calcium, creatinine, and urea nitrogen, liver and thyroid function, and serum vitamin B12 level • Optional tests not routinely recommended • human immunodeficiency virus serology, • syphilis serology, • lumbar puncture, and • electroencephalography.

9. Testing • Radiologic • identify CNS tumors, strokes, and hydrocephalus. • Invasive • Not applicable under normal circumstances • Invasive diagnostic procedures (e.g., brain biopsy) in patients with suspected dementia offer little advantage over clinical diagnosis and are unlikely to significantly alter clinical management; thus, they should only be considered in patients with an unusual clinical course

10. Differential Diagnosis • Rule out conditions or disorders that may mimic a neurodegenerative dementia • normal age-related behaviors • medication-induced confusion/dementia • focal deficits that point to specific conditions/diseases • basic laboratory studies • hypothyroidism, B12 or folate deficiency, syphilis, AIDS • Neuroimaging • subdural hematoma, tumor, and infarcts • Mental Illness • Depression

11. Causes of Dementia in Adults by Etiologic Category • Neurodegenerative Disorders • Alzheimer s disease • Down syndrome • Parkinson's disease • Dementia with Lewy bodies • Frontotemporal dementias: • Pick s disease • Frontotemporal lobar degeneration, including frontal-lobe dementia, frontal-lobe dementia associated with motor-neuron disease, progressive nonfluent aphasia, semantic dementia • Tauopathies • Frontotemporal dementia with parkinsonism linked to chromosome • Familial progressive subcortical gliosis • Familial multiple system tauopathy • Corticobasal degeneration • Progressive supranuclear palsy • Multiple system atrophy • Huntington disease • Mesolimbocortical dementia • Amyotrophic lateral sclerosis (ALS)-parkinsonism-dementia complex • Argyrophilic brain disease

12. Causes of Dementia in Adults by Etiologic Category • Cerebrovascular Disorders • Vascular dementias: • Multi-infarct dementia • Subacute arteriosclerotic encephalopathy (Binswanger s disease) • Amyloid angiopathy • Hereditary cerebral hemorrhage with amyloidosis-Dutch Type (HCWA-D) • Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) • Hippocampal sclerosis • Vasculitis • Subarachnoid hemorrhage • Neurocognitive disorders associated with cardiac bypass

13. Causes of Dementia in Adults by Etiologic Category • Prion-Associated Disorders • Creutzfeldt-Jakob disease • Variant Creutzfeldt-Jakob disease (linked to bovine spongiform encephalopathy) • Gerstmann-Sträussler-Scheinker disease • Fatal familial insomnia • Neurogenetic Disorders • Spinocerebellar ataxias • Dentatorubral-pallidoluysian atrophy • Hallervorden-Spatz disease • Gangliosidoses • Kufs disease (adult neuronal ceroid lipofuscinosis) • Machado-Joseph disease (Azorean disease) • Lafora's disease • Mitochondrial encephalopathies • Myotonic dystrophy • Porphyrias • Hepatolenticular degeneration (Wilson s disease)

14. Causes of Dementia in Adults by Etiologic Category • Infectious Disorders • Meningitis (e.g., tuberculosis) • Encephalitis: •  Herpes simplex •  Human immunodeficiency virus • Lye disease • Progressive multifocal leukoencephalopathy • Neurosyphilis • Whipple s disease • Toxic/Metabolic Encephalopathies • Systemic • Thyroid, parathyroid, pituitary, adrenal, liver, pulmonary, pancreas, kidney, or blood disorders • Sarcoidosis • Sjögren s syndrome • Systemic lupus erythematosus • Hyperlipidemia • Nutritional deficiencies (vitamins B1, B12) • Fluid and electrolyte abnormalities • Hypoglycemia • Hypoxic/ischemic disorders • Toxic: • Drugs • Alcohol • Industrial agents • Heavy metals (Pb, Hg, Mn, Ar, Th, Al, Sn, Bi) • Carbon monoxide

15. Diagnostic Criteria • DSM-IV criteria • Development of multiple cognitive deficits:1. Memory impairment, and2. At least one of the following:   Aphasia   Apraxia   Agnosia • Disturbed executive functioning (planning, organizing, sequencing, abstracting). • Course is characterized by continued gradual cognitive and functional decline. • Deficits are sufficient to interfere significantly with social and occupational functioning and represent a decline from past functioning. • Other causes (medical, neurologic, psychiatric) of dementia are excluded.

16. Diagnostic Criteria • NINCDS-ADRDA Probable Alzheimer's Disease • Dementia established by examination and documented by objective testing for: • Deficits in two or more cognitive areas • Progressive worsening of memory and other cognitive functions • No disturbance in consciousness • Onset between 40 and 90 years of age • Absence of systemic disorders or other brain diseases that could account for the progressive deficits in memory and cognition • Diagnosis supported by: • Progressive deficits in language (aphasia), motor skills (apraxia), and perception (agnosia) • Impaired activities of daily living and altered patterns of behavior • Family history of similar disorders • Consistent laboratory or radiologic results (e.g., cerebral atrophy on computed tomography NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association

17. Diagnostic Indicators for the More Common Non-Alzheimer Dementias • Dementia with Lewy bodies • Presence of dementia and at least one of the following three features early in the disease course: • visual hallucinations, • parkinsonism, and • fluctuating cognitive status • Vascular dementia (VaD) • Presence of dementia with abrupt onset • within 3 months of stroke or • abrupt deterioration or • stepwise progression of dementia, and fluctuating course • Frontotemporal dementias • Presence of dementia with • disinhibition, impulsivity, impaired judgment, and/or • amotivational states resulting in disturbed personality, behavior, and language • Depression • Presence of dementia with noncognitive changes (lack of interest, loss of energy, and difficulty in concentrating)

18. Treatment • Medical Therapy • focus pharmacotherapy • palliation of cognitive symptoms and • slowing of disease progression • cholinesterase inhibitors donepezil or rivastigmine • Contraindications for this therapy • cardiac and gastroenteric complications • antioxidant therapy as a treatment strategy for AD • Evidence for increased oxidative stress and free radical injury in AD motivated a large-scale trial of selegiline (a monamine oxidase inhibitor) and alpha-tocopherol (vitamin E at 1000 IU b.i.d.) for moderately demented AD patients • Both compounds used independently (not in combination) delayed progression to clinical milestones (e.g. institutionalization) by approximately 8 months. • Favorable safety and cost profiles of vitamin E make it acceptable to many patients in the absence of additional studies confirming efficacy. • Neither estrogen therapy nor prednisone is recommended for the treatment of AD, based on available evidence • Prevent new insult • Treat the underlying causes of vascular dementia (VaD) (e.g., hypertension, atherosclerosis, or diabetes) • Treat reversible dementias • hypothyroidism, vitamin B12 deficiency, overmedication, depression, and opportunistic infections accompanying HIV infection • no approved therapies for dementia with Lewy bodies or frontotemporal dementias. • Treat behavioral symptoms • If moderate to severe mood, behavioral, or other neurologic disturbances are present, use psychotropic (e.g., antipsychotics and antidepressants) and antiepileptic agents for short periods of time, as appropriate

19. Lifestyle Measures • safe, supportive, and orderly environment • most contentious issues for families to deal with • driving, cooking, independent living, control of financial affairs, self-medication, and participation in community affairs • Physician and caregiver working together • Recommend establishment of durable power of attorney • for financial and health care decision-making • Recommend establishment of daily routines • Constant supervision to monitor the safety of the residential setting • Recommend driving evaluation when necessary • Driving evaluations may be obtained from independent driving evaluation centers, some occupational therapists, or from the state agency regulating driving privileges. • Nutrition and hydration • increased risk for nutritional imbalance, dehydration, and weight loss • Encourage maintenance of an active and healthy lifestyle. • Exercise • Sleep-rest. • consistent daily routine • reducing environmental stimuli in the evening, • avoiding caffeine and other stimulants, • establishing toileting routines, and • possibly the short-term use of a mild hypnotic to establish a normal sleep-cycle. • Oral hygiene

20. Invasive Procedures • Invasive approaches are not appropriate for most common dementias. • Ventricular shunting may be needed to ameliorate normal-pressure hydrocephalus, or surgical excision may be indicated for CNS neoplasms. • Complementary Medicine • Ginkgo biloba. • Ginkgo biloba is an herb with putative antioxidant and anti-inflammatory properties. Gingko may benefit persons with Alzheimer's disease or mixed dementia including Alzheimer's disease and vascular dementia • Many studies of gingko have been inconclusive: • treatment effects are weak and dropout rates have led to selection bias. More rigorous studies are in progress. • A Dutch study (the Maastrict Ginkgo Trial) employing standard designs and stringent controls found no cognitive benefit for treatment groups over placebo groups • Gingko biloba has been reported to have antiplatelet effects, requiring caution for patients on anticoagulant and aspirin therapies.

21. Complications • Monitor patients for side effects of drug regimens and for interactions with other medications • Because neuroactive compounds commonly used by the elderly can exacerbate dementia symptoms • dose reduction or discontinuation of benzodiazepines, antidepressants, and minor and major tranquilizers • Neuroleptics can induce orthostatic hypotension, which can lead to falls, fractures, stroke, or even heart attack in the elderly • If such adverse effects are suspected, discontinue or reduce the medication and routinely monitor the patient throughout treatment.

22. Special Circumstances • If dementia appears to be rapidly progressing (onset and progression measured in weeks and months as opposed to years), • consider the possibility of Creutzfeldt-Jakob disease (CJD), • a potentially transmissible dementia.CJD is a prion disease, • a member of a rare family of diseases that includes scrapie in sheep and bovine spongiform encephalopathy (BSE) in cows (popularly known as "mad cow disease").

23. When to Consult or Refer • Refer patients suspected of having a potentially treatable neurologic condition • e.g., normal-pressure hydrocephalus, mass lesion) to a neurologist or neurosurgeon for evaluation. • Consider referring patients with dementia to a dementia specialist if they • Are <55 years of age; • Have rapidly progressing dementia (e.g., possible Creutzfeldt-Jakob disease); • Have psychosis early in the course of dementia; • Have prominent focal deficits (e.g., progressive aphasia); or • Reveal neurologic abnormalities (e.g., extrapyramidal dysfunction). • Refer patients who have refractory psychological symptoms (e.g., depression) to a psychiatrist. • Refer patients and their family/caregivers who need additional reassurance or assistance to community resources and/or geriatric case managers if appropriate.

24. Prognosis • Recall that Alzheimer's disease is a treatable disorder. • Drugs can ameliorate • the cognitive and behavioral symptoms of Alzheimer's disease (AD) and • aid in maintaining activities of daily living, but progression is inevitable (as in the other most common neurodegenerative dementias). • cholinesterase inhibitors • Symptomatic progression of the disease may be delayed up to 12 months in patients with AD • The total duration of the illness averages between 7 and 10 years. • For those patients who have endstage disease, • death results from aspiration, pneumonia, pulmonary embolus, sepsis, or exhaustion resulting from lack of food and water • .Although not well studied, it is widely accepted that strokes affecting critical volumes and locations can cause irreversible dementia. • Pure vascular dementia has been over-reported in clinical studies. • Patients with presumptive vascular dementia are frequently found to have Alzheimer's disease on histological examination • Vascular dementia and mixed dementia (vascular and AD) have the same prognosis as AD alone

25. Patient Education • Disclose diagnosis of dementia to the patient and family • to allow for discussion of advance planning, treatment options, prognosis, and support groups. • Advise patients and caregivers that dementia may be less disabling • if the patient's activities are structured and surroundings are safe and familiar. • Educate caregivers regarding the signs and symptoms associated with dementia. • Advise patient, family, and caregivers that treatment of the most common dementias (AD, DLB, VaD) is symptomatic • e.g. memory and thinking may improve a little • they should not expect reversal of the symptoms of dementia from therapies available today. • Self-care Instructions • Advise patient and caregivers to learn the signs and symptoms of adverse drug reactions [and • to contact a physician promptly if an adverse reaction is suspected

26. Follow-up • Re-evaluate a patient suspected of dementia at 6- to 12-month intervals • Assess disease progression, • Confirm the diagnosis, and • Establish a prognosis

27. Prevention and Screening • Recall that insufficient evidence exists regarding the recommendation for or against routine screening for dementia with standardized tests in asymptomatic individuals. • Treat the underlying causes/risk factors of vascular dementia (VaD) (e.g., hypertension, atherosclerosis, and diabetes) to prevent stroke or additional insult following stroke. • Consider timely correction of metabolic disturbances (e.g., vitamin B12 deficiency, hypothyroidism, alcoholism) associated with dementia to reduce the incidence of subsequent dementia. • Be aware that neither estrogen therapy nor prednisone is recommended for the treatment of AD, based on available evidence • Be aware that nonsteroidal anti-inflammatory drugs (NSAIDS) are not recommended for the prevention of AD, based on available evidence • Be aware that genetic screening in patients suspected of having AD is of no diagnostic value at this time.