Neurocognitive Disorders In Late Life PDF

Chapter 9: Neurocognitive Disorders in Late Life Copyright © Springer Publishing Company, LLC. All Rights Reserved. Delirium  Rapid decline in cognitive functioning in response to a substantial change in one’s physical condition.  Impairment in attention and orienta...

Chapter 9: Neurocognitive Disorders in Late Life Copyright © Springer Publishing Company, LLC. All Rights Reserved. Delirium  Rapid decline in cognitive functioning in response to a substantial change in one’s physical condition.  Impairment in attention and orientation that develops rapidly and is caused by a medical condition (American Psychiatric Association, 2013).  Impairment is shown in at least one other area of cognitive functioning, such as memory, language, or visuospatial skills. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-5. Washington, DC: Author. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Delirium (cont’d)  Symptoms fluctuate throughout the day.  Common causes: infections, metabolic abnormalities, and medication changes.  Effects can linger long after the cause is established and treated. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Differentiating Delirium From Dementia  “Delirium unless proven otherwise.”  Delirium has more rapid onset.  Delirium associated with acute medical conditions; dementia occurs more independently of medical condition.  Delirium can lead to hallucinations.  Delirium impairs orientation to time or place.  Delirium disrupts the sleep–wake cycle. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Delirium and Urinary Tract Infections (UTIs)  Chae and Miller (2015) found that 19.4% of patients with delirium had a UTI.  They also found that 11.2% of patients with dementia had UTIs. Chae, J. H. J., & Miller, B. J. (2015). Beyond urinary tract infections (UTIs) and delirium: A systematic review of UTIs and neuropsychiatric disorders. Journal of Psychiatric Practice, 21(6), 402–411. doi:10.1097/PRA.0000000000000105 Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Delirium and Urinary Tract Infections (UTIs) (cont’d)  Balogun and Philbrick (2014) found that patients with delirium had rates of UTI ranging from 25.9% to 32%, compared to 13% of hospitalized patients without delirium.  Among patients with UTIs, rates of delirium ranged from 30% to 35%, and among hospitalized patients without UTIs, rates ranged from 7.7% to 8%. Balogun, S. A., & Philbrick, J. T. (2014). Delirium, a symptom of UTI in the elderly: Fact or fable? A systematic review. Canadian Geriatrics Journal, 17(1), 22–26. doi:10.5770/cgi.17.90 Copyright © Springer Publishing Company, LLC. All Rights Reserved. Delirium and Dementia  While clinicians must distinguish between dementia and delirium, it is important to note that ‒ Dementia increases the risk of delirium. ‒ Delirium among older adults increases the risk of dementia. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Diagnostic Terminology  Neurocognitive disorder, dementia, MCI :  All refer to a syndrome of cognitive and/or behavioral symptoms.  With a variety of underlying causes.  DSM-5 includes specifiers of “probably due to” or “possibly due to” to reflect our ability to specify the underlying probable cause with some degree of accuracy. Copyright © Springer Publishing Company, LLC. All Rights Reserved. “Dementia”  Decline from a prior level of cognitive functioning.  Severe enough to interfere with everyday activities to the extent that one becomes dependent on others for help in these areas (e.g., managing finances, preparing meals, managing medications).  Alzheimer’s disease is one of many biological processes that can cause this.  DSM-5 uses the term major neurocognitive disorder instead of dementia. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Mild Cognitive Impairment (MCI)  Other terms have included: ‒ Cognitive impairment, not dementia (CIND) ‒ Cognitive impairment not otherwise specified (NOS) ‒ Mild neurocognitive disorder Copyright © Springer Publishing Company, LLC. All Rights Reserved.  National Institute on Aging (NIA)/Alzheimer’s Association (AA) Diagnostic Criteria for MCI (Albert et al., 2011)  Set of criteria expanded awareness that: ‒ One can have Alzheimer’s disease but without symptoms severe enough to be considered “dementia.” ‒ Other conditions in addition to Alzheimer’s disease can cause MCI or dementia. ‒ While memory is usually first cognitive ability to show decline, sometimes patients first show decline in other areas (e.g., language or visuospatial ability). Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C.,... Phelps, C. H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging—Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 270–279. doi:10.1016/j.jalz.2011.03.008 Copyright © Springer Publishing Company, LLC. All Rights Reserved. Mild Cognitive Impairment  Some professionals specify: ‒ Amnestic MCI versus nonamnestic MCI, depending on which cognitive domain is affected. ‒ Single-domain MCI versus multidomain MCI—one can be impaired in more than one domain but it is not considered dementia until it interferes with everyday living. ‒ DSM-5 mild neurocognitive disorder does not include these specifications. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Mild Cognitive Impairment (cont’d)  Usually associated with Alzheimer’s disease, so  DSM-5 uses the term “mild neurocognitive disorder” to reflect how other conditions can cause this syndrome, such as strokes, TBIs, or conditions such as Parkinson’s disease. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Prevalence of Dementia  According to Plassman et al. (2007):  5% among individuals aged 71 to 79 years  24% in individuals aged 80 to 89  37% of people aged 90 and older  Well-known risk factors include low levels of education and vascular risk factors such as hypertension and diabetes.  35.6 million people throughout the world had dementia in 2010. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Prevalence of Dementia (cont’d)  This number is expected to double every 20 years, so that by 2030, 65.7 million people will have dementia.  115.4 million will have it by 2050 (Prince et al., 2013).  The number of people with dementia is increasing, but the prevalence rate of dementia may be declining (Wu et al., 2017). Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W., & Ferri, C. P. (2013). The global prevalence of dementia: A systematic review and metaanalysis. Alzheimer’s & Dementia, 9, 63–75. Wu, Y. T., Beiser, A. S., Breteler, M. M. B., Fratiglioni, L., Helmer, C., Hendrie, H. C.,... Brayne, C. (2017). The changing prevalence and incidence of dementia over time—current evidence. Nature Reviews Neurology, 13(6), 327–339. doi:10.1038/nrneurol.2017.63 Copyright © Springer Publishing Company, LLC. All Rights Reserved. Causes of Neurocognitive Disorders  When autopsies are performed on people who had dementia, patients usually are found to have more than one cause.  More than half of the individuals with dementia were found to have multiple etiologies, and only 30% had Alzheimer’s disease alone (Schneider et al., 2007). Schneider, J. A., Arvanitakis, Z., Bang, W., & Bennett, D. A. (2007). Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology, 69, 2197–2204. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Traumatic Brain Injuries  Adults aged 65 and older, children aged 0 to 4 years, and adolescents aged 15 to 19 years are the most likely to experience traumatic brain injuries (TBIs).  The highest rates of TBI-related hospitalizations and death occur among adults aged 75 years and older.  Rates of TBI increase with advancing age, with the highest rates among adults aged 85 and older.  Most common cause of TBIs among older adults are falls (60.7% of TBIs among adults aged 65 and older, followed by 7.9% caused by motor vehicle accidents). Copyright © Springer Publishing Company, LLC. All Rights Reserved. Traumatic Brain Injuries (cont’d)  Contracoup damage: When part of the brain opposite the side that was struck suffers damage. For example, being struck on the left side pushes the right side of the brain into the skull, causing damage to the right side also.  Common nontraumatic causes of brain injury include brain tumors and anoxia (oxygen deprivation). Copyright © Springer Publishing Company, LLC. All Rights Reserved. Alzheimer’s Disease  Involves the development of plaques made of amyloid (Aβ) and neurofibrillary tangles, made of tau.  Amyloid plaques develop between neurons and interfere with communication between neurons.  Microtubules in cells become twisted and develop into neurofibrillary tangles. Neurons lose their structure.  Cognitive decline and impairment are more associated with the number of neurofibrillary tangles than plaques. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Alzheimer’s Disease (cont’d)  Neurofibrillary tangles tend to develop in the hippocampus, entorhinal cortex, and other parts of the temporal lobe, before spreading to other parts of the brain, including the nucleus basalis of Meynert in the forebrain.  The nucleus basalis of Meynert contributes to the production of acetylcholine, and the supply of acetylcholine decreases.  As these areas degenerate, memory declines. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Alzheimer’s Disease: Medications  Because of the breakdown of acetylcholine, and its importance in memory, current pharmacological treatments attempt to prevent the breakdown of acetylcholine.  Acetylcholinesterase, or cholinesterase, is an enzyme that breaks down acetylcholine. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Medications (cont’d)  By inhibiting cholinesterase, the amount of acetylcholine is increased, which should improve memory functioning.  Cholinesterase inhibitors such as donepezil, galantamine, and rivastigmine are commonly prescribed for patients suspected of having Alzheimer’s disease. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Medications (cont’d)  Another medication, memantine, works as a N-methyl-D-aspartate (NMDA) receptor antagonist that is meant to decrease glutamate activity.  Both these classes of medications may lead to small improvements in functioning in patients with dementia, but cholinesterase inhibitors have side effects including weight loss and syncope in older adults. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Alzheimer’s Disease  Cannot be diagnosed definitively until autopsy of the affected individual’s brain, because of the obvious risk in obtaining a biopsy of brain tissue in a living person.  Therefore, clinicians make diagnoses such as “major neurocognitive disorder probably due to Alzheimer’s disease” or “dementia of the Alzheimer’s type” when Alzheimer’s disease seems the most likely etiology. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Alzheimer’s Disease (cont’d)  Many people who are cognitively intact throughout life are nonetheless found to have Alzheimer’s disease in their brains at autopsy.  How to answer a patient when they ask “So do I have Alzheimer’s disease or not?” Copyright © Springer Publishing Company, LLC. All Rights Reserved. Amyloid Angiopathy  Amyloid plaques also develop in the arteries and capillaries of the brain, which is known as amyloid angiopathy.  Amyloid angiopathy can cause cerebral hemorrhages to occur, and it can also cause the gradual development of cerebral microinfarctions. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Alzheimer’s Disease: Genes  A small proportion of people develop Alzheimer’s disease through mutations in: ‒ The amyloid precursor protein (APP) gene on chromosome 21 ‒ Presenilin 1 (PSEN1) on chromosome 14 ‒ Presenilin 2 (PSEN2) on chromosome 1  These rare mutations lead to development of the disease, as early as one’s 40s or 50s. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Genes (cont’d)  The ε4 form of Apolipoprotein E (ApoE ε4) increases the probability of developing Alzheimer’s disease, but does not ensure that one will develop it.  DSM-5 stipulates that ApoE ε4 is a risk factor but neither necessary nor sufficient for Alzheimer’s disease to occur. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Alzheimer’s Disease: Biomarkers  Biomarker: A quantifiable representation or marker of a specific disease process.  Examples for AD include neuroimaging findings, levels of a chemical in cerebrospinal fluid (CSF), or neuropsychological test scores. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Biomarkers (cont’d)  Well-known AD biomarkers include: ‒ Structural MRI (atrophy in medial temporal lobe) ‒ Amyloid PET ‒ Fluorodeoxyglucose (FDG)–PET ‒ CSF levels of Aβ ‒ CSF levels of tau  CSF levels of Aβ and tau are obtained through lumbar punctures, in which a needle is inserted between two lumbar vertebrae. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Biomarkers (cont’d)  NIA /AA criteria place the biomarkers for Alzheimer’s disease into two categories: ‒ Biomarkers of Aβ protein deposition, including low CSF levels of Aβ and positive PET amyloid imaging ‒ Biomarkers of “downstream” neuronal degeneration or injury, such as elevated CSF tau (including total tau and phosphorylated tau), decreased FDG uptake on PET in temporoparietal cortex, and disproportionate atrophy in the temporal and parietal cortex shown on structural MRI Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Biomarkers (cont’d)  It is important to recognize that biomarkers do not measure one’s memory or other functional abilities.  Thus, they cannot tell us if one has MCI or dementia.  They can only tell us if one has a disease. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Memory Symptoms  Decline in memory is usually the first symptom.  Patients can remember events from long ago but forget recent events.  As the hippocampus deteriorates, the brain’s ability to form new memories declines. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Memory Symptoms (cont’d)  However, memories or knowledge already established years ago remain unaffected by the disease until late in its course.  Patients may forget recent conversations, the route to return home, or how to operate a new appliance. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Cognitive Symptoms  Intact social functioning often enables the patient to compensate for memory loss (e.g., by talking around a question asked, rather than answering it, when they do not know the answer).  This can mask the symptoms of this and prevent loved ones or acquaintances from noticing a decline in the patient’s memory. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Language Symptoms  Patients often develop difficulty finding words in conversations.  Patients often use circumlocutions when they cannot recall a word, using other words or phrases to convey the desired word. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Behavioral Symptoms  As the disease spreads to the frontal lobes, patients show behavioral changes in response to damage to this area, such as: ‒ Poor social comportment (e.g., swearing, rude statements, inappropriate sexual comments) ‒ Poor planning (e.g., difficulty planning a meal or a set of errands) ‒ Poor decision making (e.g., poor financial decisions) ‒ Impulsivity (e.g., unnecessary online purchases, engaging in extramarital affairs) Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Visuospatial Symptoms  Alzheimer’s disease eventually intrudes into the posterior temporal lobes and parietal and occipital lobes.  Patients may misperceive important visual stimuli, such as picking up a television remote when the phone is ringing, or being unable to find items they wanted to purchase in the grocery store.  Visual perceptual problems may lead to difficulty entering information correctly in a checkbook or noticing that their bathroom is dirty. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alzheimer’s Disease: Posterior Cortical Atrophy  Occasionally Alzheimer’s disease develops first in places like the occipital lobe or posterior temporal lobe, causing posterior cortical atrophy.  Degeneration of the occipital lobes leads to deficits in visuospatial skills.  Early symptoms can include difficulty recognizing faces, finding things in the kitchen, house, or grocery store, or difficulty assembling new furniture. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Lewy Body Disease  Lewy body disease and Parkinson’s disease are intertwined; cognitive impairment in people with Parkinson’s disease results from the accumulation of Lewy bodies.  If cognitive symptoms develop before the onset of motor symptoms, the condition is known as Lewy body disease.  If cognitive symptoms develop after Parkinson’s disease is established, then the cognitive symptoms are attributed to Parkinson’s. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Lewy Bodies  Named after Frederick Lewy who discovered them in 1912.  Small circular bodies found in the neurons of people with Parkinson’s disease and Lewy body disease.  Composed of alpha-synuclein (α-synuclein). Copyright © Springer Publishing Company, LLC. All Rights Reserved. Lewy Bodies (cont’d)  May develop first in the reticular formation, followed by the brainstem, the limbic system, and then the neocortex.  Biomarker may be amount of α-synuclein in CSF.  Often misdiagnosed as Alzheimer’s disease Copyright © Springer Publishing Company, LLC. All Rights Reserved. Lewy Body Diagnosis in DSM-5 Consists of Core features and Suggestive features, and Probable = 1 core feature + (1 core or 1 suggestive feature) Core features: Possible = 1 core feature Suggestive features: or 1 suggestive feature  Fluctuating cognition Rapid eye movement  (REM) sleep behavior  Visual hallucinations disorder  Severe sensitivity to  Parkinsonism antipsychotic medications Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Lewy Body Disease: Cognitive Symptoms  Impairments are common in visuospatial skills and executive functioning.  Including visuospatial impairment as a core diagnostic criterion may improve sensitivity to the disease (Tiraboschi et al., 2006). Tiraboschi, P., Salmon, D. P., Hansen, L. A., Hofstetter, R. C., Thal, L. J., & Corey-Bloom, J. (2006). What best differentiates Lewy body from Alzheimer’s disease in early-stage dementia? Brain, 129, 729–735. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Lewy Body Disease: Cognitive Symptoms (cont’d)  Fluctuations in cognition can include (Ferman et al., 2004): ‒ Daytime sleep of 2 or more hours ‒ Staring into space for long periods ‒ Daytime drowsiness/lethargy ‒ Episodes of disorganized speech Ferman, T. J., Smith, G. E., Boeve, B. F., Ivnik, R. J., Petersen, R. C., Knopman, D.,... Dickson, D. W. (2004). DLB fluctuations: Specific features that reliably differentiate DLB from AD and normal aging. Neurology, 62(2), 181–187. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Lewy Body Disease: Sleep Disorder  REM sleep behavior disorder: Acting out dreams during REM sleep phase.  Dreams often involve a perceived attacker.  May develop from damage to the brainstem areas involved in the control of REM sleep, such as the reticular formation. These areas may be affected by Lewy body disease earlier than other parts of the brain. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Parkinson’s Disease  First symptoms typically include a mild tremor while hands are resting, muscular rigidity, and slowed movements.  Eventually poor balance, frequent falls, and difficulty walking occurs.  If cognitive impairment occurs after Parkinson’s disease is established, then it is termed neurocognitive disorder due to Parkinson’s disease. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Vascular Disease  Involves atherosclerotic plaques building up in cerebral arteries, causing inadequate blood supply.  When arteries become completely blocked, nearby brain areas experience ischemia.  Vascular disease can cause cognitive impairment through a slow gradual buildup of ischemic damage.  Patients can also suffer a large stroke.  Infarction = Sudden death of brain tissue caused by inadequate blood supply. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Vascular Disease (cont’d)  Most strokes are ischemic (blood supply closed off), and approximately 13% are hemorrhages, or a breakage in an artery causing blood to spill out.  Patients typically show some recovery within weeks after a stroke, but may be left with lingering cognitive deficits. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Vascular Disease: Cognitive Presentation  If vascular disease builds up gradually and slowly, declines may be seen first in processing speed and executive functioning.  Sudden strokes can cause impairments in language, visual perception, attention, executive functioning, and/or processing speed, depending on the location of the stroke. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Frontotemporal Dementia  Refers to a syndrome that results from several types of pathology in the frontal and/or temporal lobes.  Most cases of frontotemporal lobar degeneration are caused by the: ‒ Microtubule-associated protein tau (MAPT) ‒ TAR DNA-binding protein with molecular weight 43 kDa (TDP- 43) ‒ Fused-in sarcoma (FUS) protein Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Frontotemporal Dementia (cont’d)  Symptoms tend to develop in the late 50s, and patients are typically diagnosed in late 50s or early 60s.  Most common among aged 45 to 64, with 60% of cases diagnosed in this age group. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Frontotemporal Dementia (cont’d)  Often mistaken as a new-onset psychiatric disorder  Has a behavioral variant and language variant.  Behavioral variant: Behavioral changes that interfere with social/occupational functioning, such as: ‒ Inability to inhibit socially inappropriate behaviors. ‒ Making poor decisions (e.g., risky financial decisions) ‒ Loss of initiative to complete basic activities of daily living (e.g., bathing) Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Frontotemporal Dementia (cont’d)  Language variant: ‒ Primary progressive aphasia: Development of language impairments as first symptom ‒ Currently divided into nonfluent/agrammatic, semantic, and logopenic subtypes ‒ Can involve nonfluent speech, poor word-finding, and/or loss of semantic knowledge ‒ Can be caused by Alzheimer’s disease or frontotemporal pathology Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Alcohol-Related Dementia  Can develop after years of excessive alcohol use.  Might result from direct effects of alcohol, or from deficiency of thiamine (vitamin B1), or both.  People with a history of alcohol abuse also are more likely to have histories of head injuries, use of other substances, and vascular risk factors.  This complicates the establishment of a direct relationship between alcohol and cognitive impairment. Copyright © Springer Publishing Company, LLC. All Rights Reserved.