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dementia; Alzheimer's disease & related dementias (ADRD)

- a group of acquired mental disorders involving general loss of intellectual abilities, including memory, language, judgment, & abstract thinking, such as to interfere with activities of daily living - there may be associated poor impulse control &/or personality change - dementias may be progressive, reversible, or static & have a variety of causes Etiology: 1) Alzheimer's disease (most common cause of dementia) 2) vascular dementia & mixed dementia - high incidence of cerebral emboli (not from carotids) [23] - atrial fibrillation [58] - ischemic stroke, lacunar infarct - leukoaraiosis (pericyte dysfunction?) - cerebral amyloid angiopathy - primary CNS angiitis - intracerebral atherosclerosis [55] 3) parkinsonism a) Parkinson plus syndromes b) diffuse Lewy body disease 4) Huntington's disease 5) frontotemporal disease, Pick's disease 6) progressive supranuclear palsy 7) corticobasal ganglionic degeneration 8) progressive ataxic syndromes 9) CNS infections a) neurosyphilis b) transmissible spongiform encephalopathy - Creutzfeldt-Jakob disease - most common cause of rapidly progressive dementia [3] c) HIV, AIDS dementia complex, possibly latent CMV [15] 10) hydrocephalus: normal pressure hydrocephalus 11) mass lesions a) frontal & temporal lobe tumors b) chronic subdural hematoma 12) metabolic & endocrine disorders, toxins - carbon monoxide poisoning [100] 13) head trauma, traumatic brain injury 14) also see CAIDE 15) also see causes of dementia & risk factors for dementia & NIH consensus statement [8] Epidemiology: - 6.5% of population > 65 years of age [31] - prevalence of dementia in population >=65 years declined from 12.2% in 2000 to 8.5% in 2016 in parallel with an increase in level of education [92] - 60% of population 95-99 years of age [33] - 35-50% of population > 85 years of age - 60-70% of dementia is due to Alzheimer's disease - 15-25% of dementia is due to Lewy body dementia - 15-20% of dementia is due to vascular dementia often coexisting with Alzheimer's disease - 2-5% of dementia due to reversible causes [21] - incidence of dementia declined 20% per decade from 1977-2008, limited to person with at least a high school diploma [48] - most expensive health care cost in U.S. 2013 at $159-$215 billion/year [28] - rates of dementia lowest for whites 11.5 per 1000 person years (at 69 years of age) - relative risk of dementia (to whites) - Native Americans: 1.05, Asians: 1.2, Blacks: 1.5, Hispanics: 1.9 [33,79,87] - socioeconomic status may contribute [39] - Asian Americans may be particularly vulnerable to the disgrace of chronic & severe mental illness [40] - dementia prevalence in older adults (>= 65 years) declined in U.S. from 2000 to 2012 from 11.6% to 8.8%, possibly associated with higher educational attainment [53]* * this despite higher prevalence of cardiovascular disease & cardiovascular risk factors [53] History: 1) time course of intellectual decline 2) functional assessment -> activities of daily living 3) education level 4) medication history 5) associated medical conditions 6) history of depression 7) history of sleep disorder 8) history of alcohol use 9) family history of dementia 10) substantiation from spouse or family member Clinical manifestations: 1) insidious onset - see subjective memory problems in the elderly - see Alzheimer's disease - see cognitive impairment in the elderly - personality, behavior, & mood changes common at the onset of dementia [8] - personality changes may include apathy, egocentricity, increased impulsivity poor emotional control, irritability, agitation, reduced impulse control - personality changes may precede recognition of cognition impairment - personality changes may mask or coincide with underlying executive dysfunction [8] 2) stable course of a period of 24 or more hours 3) clear consciousness 4) attention is normal except in severe cases 5) cognition is globally impaired a) memory impairment b) language impairment c) disorder of abstract thinking d) loss of constructional abilities 6) decline in social & occupational skills 7) loss of activities of daily living* 8) getting lost in familiar places is pathological & consistent with dementia [8] 9) hallucinations are usually absent - generally visual hallucinations when they do occur [8] 10) persecutory delusions (generally plausible) a) stolen belongings b) spouse infidelity 11) orientation is usually impaired 12) psychomotor activity is usually normal 13) patient has difficulty in finding words & often perseverates 14) behavioral disturbances & personality changes (80-100%) [8] a) personality changes are common at the onset of dementia, including apathy, egocentricity, mistust, irritability, impulsivity (pathologic gambling), emotional lability b) may result from 1] mood disorders: depression, anxiety, apathy 2] agitation resulting in verbal & physical aggression 3] wandering, pacing, rummaging 4] disinhibition c) especially prominent with moderate to severe dementia d) most patients show 2 or more behavioral disturbances e) also see Alzheimer's disease Clinical manifestations 15) involuntary movements are generally absent 16) often no underlying physical illness or drug toxicity 17) cortical dementia: a) aphasia b) agnosia c) apraxia 18) frontal-subcortical dementia: a) psychomotor slowing b) apathy c) impaired executive function d) difficulty with information retrieval 19) clues to potentially reversible dementia [3] a) rapid or abrupt onset b) fluctuating severity c) hypersomnolence d) inattention e) tremulousness f) gait unsteadiness g) hallucinations 20) triad of gait ataxia, urinary incontinence & dementia suggests normal pressure hydrocephalus 21) final stages of dementia are characterized by pneumonia, dypsnea, fevers, eating problems [19] * clinical diagnosis of dementia requires cognitive impairment that interferes with activities of daily living [104] - also see diagnostic criteria for dementia Laboratory: (Laboratory Evaluation of Dementia) 1) routine a) complete blood count (CBC) b) comprehensive metabolic panel 1] electrolytes 2] serum Ca+2 & serum albumin 3] liver function tests 4] renal function tests c) thyroid function tests d) serum vitamin B12 &/or serum methylmalonic acid (vitamin B12 deficiency) e) urinalysis 2) optional testing a) HIV testing b) serology for Lyme disease c) serologic test for syphilis (VDRL, RPR) [8] d) low serum folate levels associated with dementia e) low serum homocysteine associated with dementia f) lumbar puncture (CSF evaluation) 1] prion-related disorders (CJ disease) 2] teriary syphilis 3] meningeal carcinomatosis 4] CNS vasculitis g) urine toxin screen h) apolipoprotein E 3) occasionally helpful tests a) parathyroid function: serum PTH b) adrenal function: cosyntropin-stimulation test c) urine heavy metals d) erythrocyte sedimentation rate (ESR) Special laboratory: 1) mental status examination a) mini-Cog b) Folstein mini-mental status examination - Sweet 16 simpler & faster c) Montreal cognitive assessment tool (MoCA) - MoCA takes priority over screening for depression [103] d) time & change test 2) neuropsychologic testing a) high-functioning patients b) patients with mental retardation c) patients with low levels of education 4) Framingham Risk Score predicts dementia [75] 5) screening for depression 6) CAGE questions (screening for alcoholism) 7) occasionally helpful tests a) electroencephalogram (EEG) b) brain biopsy (rarely if ever necessary) Radiology: 1) indications for neuroimaging a) onset before 60 years of age - the American Academy of Neurology affirms neuroimaging is appropriate in the routine initial evaluation of patients with dementia [99] b) cognitive decline < 6 month duration c) focal signs/symptoms or papilledema d) new onset seizures e) ataxic or apraxic gait 2) computed tomography (CT) of the brain (without contrast) 3) magnetic resonance imaging (MRI) of the brain a) imaging modality of choice b) may be more useful for patients with suspected vascular dementia c) T2-weighted white matter changes are generally unrelated to dementia d) large pervascular space dilation in both the basal ganglia & the centrum semiovale, or in the centrum semiovale alone associated with a decline in global cognition over 4 years [80] 4) transcranial magnetic stimulation [72] - reliably & selectively distinguishes - Alzheimer's disease - Lewy body dementia - frontotemporal dementia - Huntington's disease [72] 5) positron emission tomography (PET) or SPECT [10] a) may be helpful for distinguishing Alzheimer's disease from frontotemporal dementia b) community-based PET scans may be unreliable [34] c) amyloid PET: both amyloid-positive & amyloid-negative results associated with changes in diagnosis & treatment d) marked personality change 6) angiogram of the brain may be helpful 7) chest X-ray (optional testing) Differential diagnosis: 1) delirium (see dementia vs delirium) 2) psychosis 3) depression (see depressive pseudodementia) - depression is common in demented patients 4) apathy - apathy is common in demented patients & affects ADLs beyond the level of cognitive impairment 5) minimal cognitive impairment - no impairment in activities of daily living 6 hepatic encephalopathy - fibrosis-4 score > 2.67 [106] 7) also see - differential diagnosis types of dementia - dementia vs delirium vs depression - cortical versus frontal-subcortical dementia Complications: - increased risk of hospitalizations [22] - infection-related hospitalizations associated with increased risk of mortality (RR-3 vs non-demented patients) [76] - infections & eating problems are the most common problems requiring management decisions in patients with advanced dementia [46] - pneumonia is common cause of mortality in patients with advanced dementia - sepsis associated with increased in-hospital mortality relative to non-demented patients [76] - vulnerability to scams in older patients is associated with cognitive impairment & Alzheimer dementia [68] - polypharmacy - 72% of elderly with dementia are prescribed >= 5 medications, 43% >= 10 medications [85] - these medications often include highly sedating & anticholinergic agents [85] - 1 in 7 elderly with dementia who live outside nursing homes have overlapping prescriptions for >= 3 drugs that act on the central nervous system according to Medicare part D claims [82] increasing risks for falls, respiratory depression, & cognitive impairment - increased risk of suicide within 1st year of dementia diagnosis [90,91] - injury-related emergency department visits [98] - no difference between residents in memory care assisted living & general assisted living [98] Management: === general === 1) depends upon underlying etiology - screen for depression 2) treat underlying cause when possible 3) manage associated behavioral & affective disorders - identify & treat hunger & thirst, urinary retention, constipation, infection & pain or discomfort [102] - see psychosis & agitation in the elderly (Management: section) - environmental strategies - quitting smoking reduces risk of dementia, but cutting back may be of no benefit [96] - pharmacologic agents (start low, go slow) - antidepressants with minimal anticholinergic effects: - SSRI (agents of choice in elderly) - trazodone, nortriptyline (avoid tricyclic antidepressants) [3] - patients generally tolerate discontinuation of SSRIs without recurrence of symptoms initiating treatment [24] - carbamazepine - haloperidol - benzodiazepines may result in paradoxical agitation - agents used to manage hypersexuality in men [4]: - cimetidine, SSRI, medroxyprogesterone, estrogens, GNRH analogues (leuprolide) - periodically evaluate need for continued therapy 4) treat comorbidities - treating depression in patients with dementia is controverial [24,27] - treat pain (see pain & assessment of pain in patients with dementia) 5) maximize functional skills of the patient 6) address legal & financial issues at the time of diagnosis 7) monitor the needs of the caregiver - increased incidence of depression - increased incidence of stress-related illnesses 8) telehealth is a cost-effective alternative to in home visits [74] === pharmaceutical agents === 1) also see Alzheimer's disease (Alzheimer's agents) 2) see drugs to avoid in patients with dementia 3) no effective pharmacotherapy to prevent mild cognitive impairment or slow its transition to dementia [3] 4) pharmacologic & nonpharmacologic interventions for mild- to-moderate dementia may yield statistically significant benefits of unknown clinical importance [41] 5) cholinesterase inhibitors, memantine, & statins inappropriate in patients with advanced dementia [45] === other === 1) cognitive training of no benefit [61] 2) moderate-intense exercise does not improve cognition - improves physical fitness - may contribute to cognitive decline - complications include exercise-induced angina, falls, & worsening hip pain 3) bright light +/- melatonin may reduce cognitive decline & improve physical function [18] - phototherapy improves cognitive function in demented elderly assessed by the Folstein mini-mental status examination (MMSE) [101] 4) dementia is a reportable disorder & must be reported to the heath department - see dementia, driving & California state law 5) advanced dementia a) unclear whether thickened liquid diet benefits patients with Alzheimer's disease & related dementias & dysphagia [105] b) enteral feeding not recommended in patients with advanced dementia - does not prolong life, improve quality of life, reduce pain, improve psychotic or behavioral symptoms, improve family or caregiver outcomes [37] - some evidence for risk of pressure ulcers from enteral tube feeding [37] c) cholinesterase inhibitors, memantine, & statins inappropriate in patients with advanced dementia [45] 6) prognosis (see prognosis for patients with dementia) 7) prevention: see - prevention of cognitive impairment - prevention of Alzheimer's disease Notes: - cognitive assessment for the diagnosis of dementia by general practitioners is more specific than sensitive [89] - false negatives more likely in elderly with less severe impairment - false positives may occur in those with depression [89] - emergency department visits tend to occur before & after a diagnosis of dementia [107]

Interactions

disease interactions

Related

ACE inhibitors & dementia cardiovascular risk factors, aging, & dementia (CAIDE) trial causes of dementia cortical versus frontal-subcortical dementia dementia vs delirium vs depression dementia, driving & California state law depressive pseudodementia diagnostic criteria for dementia (DSM III/IV/V) differential diagnosis types of dementia drugs to avoid in patients with dementia encephalopathy neuropsychological battery for dementia evaluation prediction of dementia prevention of Alzheimer's disease/dementia prevention of cognitive impairment prognosis for patients with dementia risk factors for dementia screening for dementia; screening for cognitive impairment; screening for Alzheimer's disease

Specific

Alzheimer's disease (AD) autoimmune dementia dementia pugilistica familial British dementia (cerebral amyloid angiopathy ITM2B-related type 1, CAA-ITM2B1) familial Danish dementia (cerebral amyloid angiopathy ITM2B-related type 2, CAA-ITM2B2, heredopathia ophthalmo-oto-encephalica) frontal-subcortical dementia frontotemporal dementia; frontotemporal lobar degeneration; frontotemporal neurocognitive disorder (FTD, FTLD) Lewy body dementia mixed dementia Parkinson's dementia; Parkinson's psychosis-dementia complex rapidly progressive dementia semantic dementia vascular dementia

General

chronic neurologic disease cognitive impairment

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