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.
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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, and 2. 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
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 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.