Neuropsychology PDF

College 1 Neuropsychology Exam: 40MC (60%) + 4 open (40%) Chronological age: measured in units of time (months or years) that have elapsed since birth Biological age: where people stand relative to the number of years they will live (in terms of the body’s organ system and physical appearance) Func...

College 1 Neuropsychology Exam: 40MC (60%) + 4 open (40%) Chronological age: measured in units of time (months or years) that have elapsed since birth Biological age: where people stand relative to the number of years they will live (in terms of the body’s organ system and physical appearance) Functional age: person’s competence in carrying out specific tasks The third age: between retirement form work force and start of age-imposed limitations o People no longer have the responsibility for the upbringing of their children, nor are they obliged to participate in the labour force The fourth age: cognitive and physical impairments interfering with everyday functioning o The number of losses in physical health and social relationships exceed the number of gains Psychological age: refers to how well a person adapts to changing conditions Social age: views held by most members of a society about what individuals in a particular chronological age group should do and how they should behave 2 models of ageing 1. The selective optimization with compensation model of ageing Individuals engage in adaptation throughout their lives. They are capable of learning and changing and calling upon extra (reserve) capacity that they might not need to use under ordinary circumstances. Selection = a strategy of concentrating efforts on domains in which effective functioning is most likely to remain high Optimization = a strategy of focusing on behaviors that maximize not only the quantity but also the quality of life Compensation = refers to substituting new strategies when losses occur 2. The ecological model of ageing The interaction between a person competence and environment results in some level of adaptation (measured in a person’s emotional well-being) A person with high competence will adapt positively to a wider range of environmental press than a person with low competence Competence = physical, sensory, cognitive and social capabilities Biology of Ageing Aging in the absence of any disease is rare… Morbidity: refers to illness and disease Mortality: refers to death Morbidity does not necessarily result in mortality Health =  The freedom of disease A state of complete physical, mental and social well-being and not merely the absence of disease Life span: the maximum that member of a species can live (max +- 120 years) Life expectancy: the average number of years that individuals in a particular birth cohort can be expected to live. 2 theories 1. Biological aging occurs within the organism regardless of outside forces 2. Biological aging is influenced by our environment and daily habits and the way we cope with life’s challenges Primary aging: Unavoidable biological process that affects all members of a species (universal) Is set in motion early in life and progress gradually over time Is intrinsic: is determined by factors within the organism Secondary aging Experienced by most, but not necessarily all members of a species Resulting from hostile environmental influences fe. Smoking Programmed theories: consider aging to be under the control of a genetically based blueprint – related to primary aging Time Clock Theory: o Cells form human infant doubles 50 times, whereas cells from a mouse doubled 10-15 times o Life span is controlled by genetically determined time clock at cellular level Immune Theory: o Immune system is programmed to maintain its efficiency for a certain amount of time, after which it starts to decline § Inferior antibodies: mistakenly attack and destroy normal cells Evolutionary Theory: o Members of species are genetically programmed to bear and rear their young. Once they reproduce and raise their offspring to independence, they have fulfilled their service in perpetuating the species. § Fruit flies forced to delay reproduction lived longer than fruit flies that reproduced early Stochastic Theories: Focus on random damage to our vital systems that occurs with the process of aging – related to secondary aging Error theory: o Errors occur at cellular level resulting in the production of faulty molecules. o Cells have a repair mechanism, but may not keep up with damage created by faulty molecules  Wear and tear theory: o We begin living with a fixed amount of physiological energy. If we expend it quickly, aging begins early and proceeds rapidly. Stress theory: o Stress triggers physiological activation that results in secretion of stress- related hormones. § Young organism: stress system quickly returns to normal levels § Older organism: stress system needs more time to return to normal levels o Stress-related damage to the biological system can accelerate the aging process. Aging is the result of an interaction between both nature and nurture Aging is accompanied by a lot of physical changes Skin and hair Musculoskeletal system Cardiovascular system Normative aging: what is considered a usual, normal, or average outcome Successful aging: what is considered an ideal rather than average outcome Is a combination of 3 elements: absence of disease, maintenance of physical and cognitive abilities, and engagement in productive activities Positive aging: the ability to find happiness and well-being even in the face of physical and/or psychological challenges Active aging: the process of optimizing opportunities for health, participation and security to enhance quality of life as people age 2 hypotheses about the relation between health problems Compression of morbidity o States that the most severe health problems are concentrated in the last years of life o “If we live longer, then we experience more years in good health” Expansion of morbidity: o States that the number of life years in poor health increases with an increasing lifespan o “If we live longer, then we also spend more years battling health problems” College 2 fMRI à activation in brain PET à radioactivity Structural changes Grey matter Stable: Primary visual cortex + entorhinal cortex Reducing in volume: caudate nucleus + lateral prefrontal cortex + cerebellar hemispheres + hippocampus Frontal lobes show the fastest (=steepest) rate of reducing o Parietal lobe is second Declines becomes steeper with increasing age White matter Greatest white matter loss in frontal regions Anterior to posterior gradient: front declines more than back of the brain Increase in cerebrospinal fluid to fill up the space of the smaller brain Neurotransmitters: loss of receptors and transporters with aging Cognitive decline Crystallized pragmatics: knowledge you develop over life, remains stable Fluid mechanisms: Control processes, declines over aging. Plasticity: the brain’s ability to adapt behaviorally and neuronally to the environment Representations are generally well maintained at older ages, but some knowledge is either lost or becomes inaccessible Control processes develop at different ages and decline differentially, depending in part on the brain areas involved. 1. Speed of processing: declines with aging. 2. Working memory: declines with aging. We can keep a little less information in our working memory when we get older 3. Long-term memory: declines with aging. 4. Short-term memory: declines with aging, but smaller decline in comparison with long-term memory. 5. Verbal knowledge: increases with aging. Neural activity associated with cognition shows both age-related decreases as well as increases. 2 patterns of age-related functional activations 1. Posterior-anterior shift in aging (PASA) a. For all cognitive function, fe attention, frontal areas have an increase in activation. i. Our frontal lobe becomes more involved when we get older, but the structure reduces. b. Older adults show: i. Decreased activation in posterior(back) areas of the brain ii. Increased activation in anterior(frontal) areas of the brain iii. Additional recruitment of higher order cognitive functions allows older adults to maintain a good accuracy level, most often at the expense of slower reaction times. 2. Hemispheric asymmetry reduction in older adults (HAROLD) a. With aging, you will start to use both side of the brains instead of only one side. It becomes more symmetric. i. 2 explanations: 1. Compensation: bilateral activity (using both sides) is associated with successful cognitive performance 2. Dedifferentiation account: more widespread activation reflects an age-related difficulty in engaging specialized neural mechanisms. ii. Activations is both hemispheres are useful for performing the memory task in older adults. Cognitive aging theories Sensory Deficit theory (hearing, seeing) o Age-related deficits in sensory processing play a major role in age-related cognitive decline. o Older adults show considerable deficits in visual and auditory processing o Strong correlations between age-related differences in sensory processing and cognitive performance Resources deficit theory (attention) o Aging is associated with a reduction in the number of attentional resources. § Result: deficit in demanding cognitive tasks. § Deficits are smaller when environment provides support, fe like a memory cue o When attentional resources are reduced in younger adults, they tend to show cognitive deficits that resemble those of older adults. o Attention relies strongly on the prefrontal cortex. Speed deficit theory (slower/speed) o Older adults’ cognitive deficits reflect a general reduction in the speed of cognitive processes. o Limited time mechanism: the time required by early operations reduces the time available for later operations o Simultaneity mechanism: the products of early operations are lost or irrelevant by the time later operations are completed. o Processing speed declines steadily with age o White matter deterioration: § Deterioration of the myelin sheath around axons which support speed of neural transmission along axons o Increase of neural network that supports cognitive performance § More areas and other areas of the brain are recruited to perform a cognitive task à costs more time Inhibition deficit theory (ability to inhibit information) o Age-related cognitive decline is due to a decline in the inhibitory control of working memory contents. § When inhibitory control fails, goal-irrelevant information gains access to working memory.  o Regions that exert inhibition (inhibitory control regions): often anterior regions (front) o Regions that are inhibited: often posterior regions (back) o Older adults show weaker activity than younger adults in inhibitory control regions o Older adults show greater activity in regions that are supposed to be inhibited than younger adults Scaffolding theory of aging and cognition (model that combines all the above theories)!! o Behavioral performance of older adults: § Combined influence of age-related neurocognitive decline + age-related compensation o This model acknowledges that the aging brain must adapt to neural challenges including atrophy. § To cope with this: the brain builds alternative neural circuitry, or scaffolds Scaffolds: represent compensatory strategies and allow older adults to maintain a high level of activation o Summary points!! 1. The basic hardware of cognition significantly declines with advanced age, although knowledge and expertise are relatively protected from age related decline. Neural structures also show changes. Many brain structures show significant shrinkage, the integrity of the white matter decreases, and dopamine depletion occurs. 2. In contrast to age-related declines in cognitive function and brain structure, functional brain activity increases with age, particularly in the frontal cortex. The proposed scaffolding theory of aging and cognition suggests that this increased functional activity is due to compensatory scaffolding, i.e. the recruitment of additional circuitry with age that shores up declining structures whose function has become noisy, inefficient, or both. 3. Prefrontal cortex is the most flexible structure of the brain, and brain scaffolding processes in the aging brain largely reside in this structure. 4. Scaffolding is the brain’s response to cognitive challenge and is not unique to aging. Aging simply results in more frequent cognitive challenges at lower levels of intensity. 5. Scaffolded networks that develop with age may be less efficient than the original, direct and finely honed networks developed at younger ages. 6. The aged brain is less efficient at generating scaffolding, and significant pathology (as occurs in e.g. Alzheimer’s disease) may entirely limit scaffolding operations. Individual differences Decline in brain structure is niet gelijk aan the severity of cognitive decline Cognitive reserve: Individual differences in cognitive processes or neural networks underlying task performance allow some people to cope better with decline in brain structures than others. Cognitive reserve is measured with intelligence, education, work level, literacy, social relations etc. Better cognitive reserve is protective against age-related changes People with a low cognitive reserve: Show relatively early a decline in cognitive performance relative to the decline in brain structures People with a high cognitive reserve: Show relatively late a decline in cognitive performance relative to the decline in brain structures. 3 factors that have a major influence on cognitive performance 1. Age 2. Level of education a. Memory 3. Gender a. Women recognize emotions better than men, especially fear, anger and sadness. Always compare a performance with the performances of people of the same age, the same gender and the same level of education Something is considered “impaired” when a person obtains a score that is 2 Standard Deviations below the average of the normative data sample. 2 self-regulatory strategies to support successful adaptation Selective Optimization with Compensation (SOC) o Selection refers to the process by which individuals choose tasks that are of high individual importance and that match their abilities § Elective selection: based on preferences and social norms § Loss-based selection: refers to a shift in personal goals due to a loss of internal or external resources Resource Orchestration o This approach involves: § Defining meaningful goals § Identifying key cognitive abilities relevant to these goals § Optimizing decisions when to use strategies to achieve the best possible match between variable environmental demands and individual goals Cognitive reserve model: Suggests that the brain actively attempts to cope with brain damage by using preexisting cognitive processing approaches or by enlisting compensatory approaches Neural compensation: refers to the process by which individuals suffering from brain pathology use brain structures or networks not normally used by individuals with intact brains to compensate for brain damage. Theories of aging Dedifferentiation theory o Neural specificity decreases in older adults, meaning brain regions that were selective in younger adults respond to a broader range of inputs in aging brains à “dedifferentiation” Processing speed theory o Slowed processing speed impacts cognition in 2 ways: § Cognitive tasks take longer to complete § Less information is available for higher-order processes due to the delay of earlier processing results Scaffolding theory: o Posits that the brain adapts to age-related structural changes by strengthening existing neural connections, forming new ones, and discarding weaker pathways o Scaffolding occurs as the brain’s response to challenges allowing it to maintain cognitive function despite neural degradation College 3 Dementia is a syndrome due to disease of the brain, usually chronic, characterized by a progressive deterioration in intellect including memory, learning, orientation, language, comprehension and judgment. Main risk factor à age There is no treatment available that cure dementia o But there are treatments that are symptomatic Mild cognitive impairment: subjective and objective cognitive symptoms greater than expected for an individual’s age and education level which do not interfere with activities of daily life Transition stage between normal aging and dementia Diagnostic criteria o 1. Concern regarding cognition o 2. Impairment in one or more cognitive domains o 3. Preservation of independence in functional abilities o 4. Not demented Subtypes o Amnesic: there are memory impairments o Non-amnesic: impairments are present in cognitive domains other than memory o Single domain: impairments are evident in one cognitive domain o Multiple domain: impairments are evident in more than one cognitive domain. o  Metabolic features: etiology o Thyroid dysfunction o Dysfunction of other hormones o Vitamin B12 deficiency 45% stable mci and 35% progression to Alzheimer or dementia Preclinical stage: silent phase: brain changes without measurable symptoms Amnesic MCI à higher likelihood of progressing to Alzheimer o + individuals with impairments across multiple cognitive domains in MCI are at greater risk of progression into Alzheimer Non-Amnesic MCI à greater likelihood of stabilization or reversion Alzheimer’s disease: a degenerative brain disorder characterized by progressive intellectual and behavioral deterioration Symptomatically usually dominated by memory disorder, with prominent visuospatial and language impairment in the context, at least early in the course, of preserved social skills Life span after diagnosis generally about 10 years Usually after age 65 Insidious onset and gradual progression Pathology: o Plaque formation begins with abnormal misfolding of beta amyloid protein à leads to neurofibrillary tangles à consequence: synaptic disruption and neurodegeneration Alzheimer’s disease, by definition: progressive memory impairment Mild stages Alzheimer: clues and multiple choices usually improve retrieval and recognition of forgotten items. Moderate stages often start when the memory impairment affects activities of daily living. Severe stages: even the most overlearned memories are starting to be lost or inaccessible, including recognition of close family or even of personal identity. Memory impairments are related to degeneration of hippocampus and entorhinal cortex  First affected: your explicit/declarative memory, this consists of episodic and semantic memory Long term memory assessment: Rey Auditory Verbal Learning Test o Evaluation of encoding, consolidation and retrieval In moderate and severe stages à working memory is affected Visuospatial and perceptual functions o Fe. Getting lost in familiar places, inability to match socks, difficulty locating misplaced objects, non-recognition of common objects and their use o It occurs early but is in general not clinically apparent until memory and attentional disturbances are fully established Language o Fe. Word finding difficulties, speech becomes less spontaneous, speech becomes empty o Aphasia: the acquired disturbance of language secondary to brain damage o Moderate stages: language remains fluent with preserved repetition. Basic language structure is intact o Severe stage: people become dysprosodic (losing emotion in language) some people develop reiterative speech disturbances, fe. Echolalia: repeating others’ words and phrases. Finally, people become mute o General conclusion: in Alzheimer both output (speech and writing) and input (auditory and reading) are affected Apraxia o A family of cognitive motor disorder that entail the loss or impairment of the ability to program motor systems to perform purposeful skilled movements § 2 types: Ideational: failure to the sequence of events, fe lighting a cigarette Ideomotor: inability to do imitate an act that can be performed automatically, fe. Brushing teeth Attention & executive functioning o People become distractible and have a poor concentration o Impairments in executive functions are already present in the mild stages of Alzheimer § Impairments in executive functions often underlie problems with activities of daily living o  Personality and social behavior o Personality and social behavior are broadly preserved Apathy o = lack of motivation relative to the person’s baseline state. Ranges from mild passivity and loss of interest o Can be misdiagnosed as depression o Most common neuropsychiatric manifestation in Alzheimer o People with apathy and Alzheimer are more dependent with regard to their activities of daily living Other neuropsychiatric issues o Delusions and hallucination o Depression § Alzheimer and depression often coexist, and symptoms overlap o Aggression The differences between depression and dementia Onset and progression o Depression: acute onset o Dementia: symptoms emerge gradually over years Cognitive and behavioral symptoms o Depression: § Frequent complaints about cognitive issues § Social withdrawal is driven by dysphoria and anhedonia o Dementia: § Cognitive symptoms often observed by others before recognized by the patient. § Apathy manifests as a lack of initiation, low emotional response, and preference for staying home Memory function  o Depression: memory issues stem from executive dysfunction, leading to difficulties with effortful recall o Dementia: memory impairments reflect poor retention of information, rapid forgetting and minimal improvement with cues Serial position effects in memory tests o Depression: U-shaped recall pattern à better recall at the beginning and end o Dementia: recency advantage due to difficulty retaining information over time Executive functioning o Depression: deficits reflect slowed processing and effort-dependent tasks o Dementia: consistent impairments independent of efforts College 4 Vascular dementia =1894: an association between atherosclerosis, reduction in cerebral perfusion and cognitive decline in older adults =Vascular pathologies aside from stroke, such as subcortical microvascular disease are related to dementia Vascular cognitive impairment = the spectrum of mild to severe cognitive deficits presumed to be caused by cerebrovascular disease o It is a spectrum from the left: vascular cognitive impairment no dementia, to the right: vascular dementia Second or third most common type of dementia worldwide There is no definitive set of pathological criteria for vascular dementia à difficult to define a gold standard for the neuropathological diagnosis of vascular dementia There are some key neuropathological features: The presence of: o Small or large vessel disease o White matter lesions § White matter hyperintensities: damage on a microlevel, frequently present in older individuals. White matter is very important for communication in the brand § Diffuse demyelination: myelin is also very important for communication § Stroke: also affects the white matter, but it is not limited to white matter o Infarcts § Ischeamic stroke: occlusion of major cerebral blood vessel or a series of small cerebral blood vessels (thickening of the vessels) Due to: o Acute blockage due to embolism o Thickening of the vascular wall § Hemorrhagic stroke Rupture of large or small cerebral blood vessels § Large vessel stroke One or more arteries supplying blood to the brain rupture of experience blockage § Small vessel stroke Blockage of the cerebral microvessels o Strongly associated with hypertension o More associated with vascular dementia o Lacunes: § Small cavities located in the subcortical and deep structures of the brain. It is not limited to white matter Vascular dementia is the result of 1. Extensive white matter lesions and lacunar infarcts due to small vessel disease a. Slow onset and a gradual decline  2. One or more strokes to the main cerebral arteries (large vessel disease) a. Abrupt onset and a stepwise decline 3. The combination of 1 and 2 A stroke in different arteries has different effect: Middle cerebral artery: middle of brain Hemiplegia Aphasia Hemianesthesia Anterior cerebral artery: front of brain Paraplegia Abulia Executive dysfunctions Personality changes Posterior cerebral artery: back of brain Homonymous hemianopia Visual agnosia Balint syndrome Prosopagnosia Clinical manifestation of vascular dementia Impairments in attention and executive functions are most salient, f.e. planning, set-shifting, inhibition, selective attention etc. Other typical features of vascular dementia: o Language: naming difficulties o Visuoperceptual skills: impaired performance on visual organization tasks o Psychomotor function: impaired performance on tests of psychomotor speed People with vascular dementia are more often depressed than people with Alzheimer’s disease due to preserved disease insight When one or more strokes occur, less pathology is needed to cause dementia Hypothesis: vascular changes stimulate the formation of Alzheimer’s disease pathology As people get older the prevalence of risk factors for vascular dementia increases: f.e. diabetes, hypertension and cerebrovascular fragility Risk factor o Cardiovascular disease à reduced cerebral blood flow Frontotemporal dementia Formerly called: Pick’s disease = a progressive neurodegenerative disease o Selectively affects the frontal and/or temporal lobes Common cause of dementia in people younger than 65 years  Atrophy in the frontal and temporal lobes Hypometabolism in the medial and lateral prefrontal cortex Inclusion of Pick bodies DSM5 criteria o The disturbance had insidious onset and gradual progression o Relative sparing of learning and memory and perceptual-motor function o Either 1 or 2: § 1. Behavioral variant: decline in social cognition and/or executive abilities § 2. Language variant: decline in language ability, in the form of speech production, word finding, object naming, grammar, or word comprehension Behavioral variant of frontotemporal dementia o Progresses relatively fast à survival time 9 years o Insidious onset of personality changes and behavioral abnormalities § Poor insight: deny the existence of illness § Loss of personal awareness § Loss of social awareness § Blunting of affect o Frontal lobe is initially affected by neurodegeneration. Neurodegeneration spreads to frontal and temporal lobes in advanced stages o bvFTD is caused by the abnormal accumulation of proteins in the brain which leads to neuronal death and brain atrophy and is called: Frontotemporal Lobar Degeneration (FTLD). Common types are: § FTLD-tau: tau protein inclusions § FTLD-TDP: TDP-43 protein inclusions o Other changes: lack of empathy, self-centeredness, emotional coldness, decreased concern about family and friends, inappropriate sexual comments o Features of obsessive-compulsive disorder can also be a behavioral change o Orbitofrontal lobe dysfunction: § Disinhibition: restlessness, irritability § Poor impulse control: aggressiveness § Antisocial behavior  § Decreases agreeableness o Anterior cingulate cortex and medial frontal lobe dysfunction § Apathy o Right Hemisphere dysfunction § Dramatic changes in beliefs, attitudes and/or religious sentiment o Many people develop a language dysfunction o Diet may change: eating more sweets/craving o Oral exploratory behavior: biting etc. o Memory and visuospatial functions are relatively spared Primary progressive aphasia: characterized by an exclusive impairment in language during the first 2 years of the disease. + behavioral changes are not present until later in the disease + executive functions and visuospatial functioning are initially preserved but decline as disease progresses + explicit memory is relatively intact o Semantic dementia: § Progressive loss of semantic knowledge or knowledge about people, objects, facts and words Daily life: misuse or inability to recognize household items such as can-opener § Presenting complaint involves language: loss of memory for words, loss of word meaning, speech is fluent, substitute phrases (“thing” or “stuff”) are often used § People with semantic dementia are most impaired on: Category fluency tests: “name as many animals as possible” Naming tasks Generation of verbal definitions of words and pictures: f.e. misidentify an orange as an apple § Is most associated with FTLD-TDP pathological changes: atrophy in the anterior temporal lobes o Non-fluent primary progressive aphasia § People present with changes in agrammatism and/or effortful speech § People report difficulties with: Loss of function words Fluency o Rate of speech o Melody of speech Pronunciation or articulation Word finding difficulties Frequent apraxia of speech (difficulty coordinating mouth movements) § Frontotemporal lobar degeneration + FTLD-tau pathological changes  Changes are in the left interior frontal gyrus, insula, premotor and motor areas o Logopenic primary progressive aphasia § Impairments in: single-word retrieval in conversation and on testing of naming to confrontation or to auditory cues Impaired repetition of sentences and phrases § People report: Slowness of speech due to word finding difficulties Paraphasic errors which tend to be more phonological (substituting words with similar sound) than semantic § Executive, visuospatial and explicit memory are initially preserved Difference from Alzheimer: memory impairments are significantly more prominent in people with Alzheimer College 5 Lewy body diseases 1. Parkinson’s disease without dementia 2. Parkinson’s disease with dementia 3. Dementia with lewy bodies 2 & 3 à Lewy body dementias Lewy bodies are neuronal inclusions, typically found in subcortical nuclei (substantia nigra) Regional distribution can vary between people with Lewy body disease o Correlating with the symptomatology Parkinson’s disease Progressive, neurodegenerative disease Caused by death of dopaminergic neurons in the substantia nigra o Not enough dopamine The cells of the substantia nigra starts to degenerate à decreased amount of dopamine o Result: § Dysfunctioning of the striatum § Dysfunctioning of the areas connected to the striatum Motor symptoms: o Tremor: trillen van de handen etc. in rust o Rigidity o Bradykinesia: slowness of the movement o Postural instability: easily out of balance Clinical appearance o Difficulties arising from chair o Difficulties walking o Difficulties with keeping balance o Frequent falls o Monotone speech Neuropsychiatric symptoms o Depression, apathy, anhedonia à 40% o Visual hallucinations à often precursor of dementia o Impulse control disorder à often due to antiparkinsonian medication Cognitive impairments of people with Parkinson’s disease progress over time o Deficits in psychomotor speed (60%), language (25%), memory (40%) and visuospatial skills (50%) and attention and executive function (90%) o People with Parkinson’s disease mainly show a degeneration of attention and psychomotor speed o >50% develop Parkinson’s disease dementia Parkinson’s disease dementia Diagnostic criteria  o First must be diagnosed with Parkinson’s disease o The is an insidious onset and gradual progression of cognitive impairments o First motor symptoms, then cognitive deficits Behavioral disorders o Visual hallucinations, agitation, excessive daytime sleepiness, depression, anxiety, apathy Impairments in retrieving information from memory à recognition is intact, and external cues have a positive effect Visuospatial impairments are more often present in people with Parkinson’s disease dementia Little cortical atrophy Functional connectivity is reduced in frontal regions More fronto-parietal hypometabolism, lower glucose metabolism Dementia with lewy bodies First cognitive impairments and then motor problems Central feature: progressive cognitive decline that interferes with normal social or occupational functioning Criteria o Criteria are met for neurocognitive disorder o Insidious onset and gradual progression o Core and suggestive diagnostic features § Core: Fluctuation in cognition o Occurs early in the course of the disease o Fluctuations can occur rapidly (minutes to hours) or gradually (days to weeks) o Also, episodes of wakeful unresponsiveness to episodes of daytime sleepiness o Fluctuations are likely due to damage to the alerting and arousal systems in the brainstem Recurrent visual hallucinations Spontaneous features of parkinsonism (motor symptoms) o But with less rest tremor o Rigidity and bradykinesia are present o Postural instability more present in DLB § Suggestive Rapid eye movement sleep behavior disorder o Movement during rem sleep, as if acting out in dreams o Rem sleep behavior often precedes dementia Neuroleptic sensitivity o Are prescribed to treat psychoses o Side effects of neuroleptics are parkinsonism, falls, drowsiness  Impairments in memory, visuospatial functions, executive function and attention Compared to Alzheimer, people with dementia with lewy bodies have more severe deficits in: o Attention, verbal fluency, visuospatial ability, executive function, psychomotor speed Memory is failing at the retrieval stage and recognition is intact Reduced dopaminergic transmission, the same as Parkinson’s disease Atrophy + reduced white matter integrity + functional connectivity is reduced in posterior regions The symptoms are alike with parkinson’s disease (dementia), but the time course is different. Progression of pathology PDD and DLB: Braak staging system: Stage I – II (preclinical) o Pathology begins in olfactory and brainstem regions Stage III -IV (clinical diagnosis) o Pathology spreads to midbrain Stage V – VI (advanced disease) o Widespread involvement of cortical association areas and neocortex Huntington’s disease Progressive, hereditary disease with an insidious onset, characterized by: o Motor symptoms, cognitive impairments and neuropsychiatric symptoms à leading to dementia Caused by a CAG repeat on chromosome 4 o 36-39 repeats à mild symptoms o 40 or more repeats à will develop Huntington Autosomal dominant disease o Every son or daughter of a gene carrier has a 50% chance to inherit the disease The cag repeats lead to degeneration of certain parts of the brain o Early stage: degeneration of the striatum, resulting in the dysfunctioning of fronto-striatal circuits § Changes in the dopaminergic neurotransmitter system o Later stage: more global atrophy of the brain Motor symptoms o Dyskinesias § Chorea: random, uncontrollable movements (most common in huntington) § Hypokinesia: decreased number of spontaneous movements o Bradykinesia: slowness of movement o Dystonia: sustained muscle contractions o Rigidity o Dysarthria: problems with mouth movements/speaking o Problems with eye movements, swallowing, keeping balance Progressive decline of cognitive functioning differs between people o Relatively mild until later stages or fast progression with an evident dementia early in the course of disease Impairments are present in the cognitive domains of psychomotor speed, executive functions, attention, memory o Memory: impairments in encoding and retrieval of information + working memory § Recognition and knowledge are intact o Psychomotor speed: slowness in thinking and in acting o Lack of insight because of executive dysfunctions § This leads to that people with Huntington rarely complain about the motor symptoms and cognitive impairments Some show changes in their affect, character and behavior. o Depression o Anxiety o Agitation o Disinhibition: no self-control o Compulsive behavior o Psychoses Treatments  o Tetrabenzine: reduces involuntary movements but may exacerbate depression o SSRI’s: used for irritability Corticobasal degeneration (CBD) = a progressive neurodegenerative disorder in which the number of brain cells in the cerebral cortex and basal ganglia decreases Disease duration: approximately 7 years from diagnosis to death Clinical presentations: o Motor dysfunctions: often asymmetric and progressive o Cognitive dysfunction: may present with primary progressive aphasia (nonfluent/agrammatic variant) o Common initial complaints: § Clumsiness, stiffness of a limb § Toe-stubbing during walking due to leg clumsiness o Cortical sensory deficits: § Astereognosis: inability to recognize objects by touch § Agraphesthesia: inability to recognize written symbols traced on skin o Alien hand syndrome: sense of disowner ship of a limb Neuropathology: o Presence of ballooned and achromatic neurons o Tau-containing neuronal inclusions o Asymmetric atrophy of the frontoparietal cortices o Neuronal loss o Decreased pigmentation and cell loss in the substantia nigra à motor dysfunction Neuroimaging: o Atrophy in the frontoparietal, temporal and occipital lobes o White matter abnormalities in motor areas o Reduced dopamine transporter binding o Reduced glucose metabolism o Reduced cortical acetylcholinesterase Neuropsychological hallmarks o Language: nonfluent aphasia, impairment in verbal fluency and phonological problems o Learning and memory: impaired recall and retrieval deficits o Neuropsychiatric features: depression, apathy and irritability Progressive Supranuclear Palsy (PSP) = a rare brain disease that affects walking, balance, eye movements and swallowing Core clinical features: o Ocular motor dysfunction: difficulty with (vertical) eye movements o Postural instability: repeated unprovoked falls, disbalance o Akinesia: inability to voluntary move one’s muscles and limbs  o Cognitive dysfunction: speech, language, frontal behavioral syndromes The most common PSP is: Richardson’s syndrome PSP à characterized by vertical gaze palsy (ogen) and postural instability Neuropathology: o PSP affects the entire substantia nigra à leading to dopamine loss o Neuronal loss o Neurofibrillary tangles are found (Alzheimer) o Damage is more widespread across the brainstem and subcortical structures Neuroimaging: o Midbrain and frontal atrophy o Reduction in glucose metabolism o Increased tau protein Neuropsychological hallmarks: o Attention and working memory: visual attention impaired and bradyphrenia (slowing of thought) o Executive functions: early deficits with rapid progression o Language: speech impairments and letter fluency deficits o Learning and memory: impaired free recall o Visuospatial: impairment in voluntary vertical eye movements and reduced blinking o Neuropsychiatric features: apathy, personality alterations, disinhibition and irritability College 6 Delirium Refers to mental disorder during fever or due to head trauma o When you go crazy/out of control Symptoms of delirium: o Inattention, disorganized thinking, memory impairment, disorientation, altered level of consciousness, acute onset, perceptual disturbance, psychomotor agitation or retardation, altered sleep-wake cycle DSM criteria o A disturbance in attention and awareness (reduced orientation to the environment) o The disturbance develops over a short period of time and tends to fluctuate in severity during a day. o An additional disturbance in cognition Delirium can be a marker for a vulnerable brain with reduced reserve capacities + delirium might lead to permanent cognitive decline and dementia Delirium causes: The etiology of delirium is often multifactorial o Energy deprivation in brain o Metabolic derangements o Central nervous system injury o Drug toxicity o Neoplasms (tumor) o Central nervous system infections Predisposing factor (non-modifiable) (vulnerability) o Older than 65 years, male sex, cognitive impairment, surgery, terminal illness, history of alcohol misuse Precipitating factor (modifiable) (insults) o Pain and emotional distress, restraints, medications, biochemical abnormalities, dehydration, infections Dementia is one of the most prominent risk factors for delirium The more predisposing factors a person has, the fewer precipitating factors are needed to tip the “sensitive balance” in older adults leading to the development of delirium Protective factors for delirium include: o Timely recognition of people who are at risk o Targeted multicomponent interventions Subtypes of delirium o Hyperactive/hyperalert: the person is confused, restless and agitated. People show psychomotor hyperactivity, abnormal alertness and arousal. People may not stay in bed, not keep clothes on and become violent when directed of resisted o Hypoactive/hypoalert: the person is confused, lethargic and often appears depressed. People show psychomotor hypoactivity and drowsiness. They may sleep excessively, become difficult to arouse, hallucinate and disturbed vocalization. o Mixed level of activity  Neuropsychiatric and cognitive symptoms associated with delirium o Neuropsychiatric § Most frequent: sleep-wake cycle disturbance 73% o Cognitive § Most frequent: Inattention 73% Recognition of delirium o Gold standard: psychiatric evaluation o Diagnosis is made on clinical grounds o Delirium affects the cortex diffusely o Delirium can have a widely variable clinical presentation of neuropsychiatric symptoms o Delirium can result in any neuropsychiatric symptom o Job of clinician: differentiating delirium from other conditions with similar/overlapping symptoms o Consequence: diagnosing of delirium is difficult and delirium is often missed, misattributed and underdiagnosed. Delirium is characterized by an acute change in baseline cognition, behavior and function in mental status. o Collateral information from family member, other caregivers, or staff members over the previous 24-48 hours is needed o People with delirium demonstrate fluctuating attention, awareness, and level of consciousness o Conflicting reports from various caregivers at different times about the person’s mental status Key findings of a person with delirium o Behavior: § Agitation Fe. People with delirium may think they are at home instead of in the hospital § Apathy or withdrawal Fe. A person with delirium may fall asleep during the interview o Affect: § Emotional lability People with delirium might show a lot of emotions in short period of time o Cognition: § Attention Fe. People with delirium often cannot attend to calculations that required sustained concentration § Disorientation Don’t know the place, date etc. § Memory Fe. Unable to recall reason for hospitalization or the care provided by the nursing staff § Language § Abstract reasoning:  Fe. Performance on similarity task is poor § Problem solving / executive functions Impaired judgement o Neglect of illness § Anosognosia People with delirium are often unconcerned and can deny being ill o Misperceptions, hallucinations, delusions § People with delirium may experience distortions of shape or size Caregivers: Wear and tear hypothesis: o Over time caregivers’ functioning steadily declines because of prolonged stress Adaptation hypothesis: o Caregivers adapt to the demands of caregiving over time and their physical and mental health stabilizes or improves  Trait hypothesis: o Despite dementia progressing, caregivers function well because of individual characteristics Caregiver burden: a multidimensional response to physical, psychological, emotional, social and financial stressors associated with the caregiving experience o Caregiver burden cannot be strictly tied to the severity of dementia or length of time someone has provided care When patients go to nursing home o Improvement: no longer dealing with unpredictable behavior and poor health status daily o Burden: increase of financial strains, loss of companionship, concerns about quality of nursing home care Caregiver predictors o Gender differences: female caregivers experience more depressive symptoms, anxiety § Women spend more time on caregiving § Great variation among individuals in the nature and impact of caregiving § Gender differences are more pronounced among adult children than among spouses § Men are certainly not immune to the effects of caregiving o Coping: is very useful when looking at caregiver burden § Emotion focused coping is associated with higher levels of distress o Personality: § Some caregivers are more likely than others to appraise a caregiving situation as stressful o Social support o Health behavior Caregiver consequences o Blood pressure: have more difficulties remaining a stable blood pressure o Increased activity of HPA axis o A poor antibody response to infections o Increasing risk of coronary heart disease o More medication use, a greater number of physical symptoms, more days of illness College 7 Intellectual disability (ID): involves significant cognitive limitations affecting daily life and typically emerges during the developmental period. Limitations in intellectual functioning and adaptive behavior (social, conceptual (language, reading), practical adaptive skills (safety, travel)) Down syndrome (DS) A subset of intellectual and developmental disabilities (IDD), is strongly linked to dementia, with affected individuals often showing symptoms earlier than those with other types of IDD Genetic cause: 3 chromosomes on 21 Risk on a child with Down is strongly associated with mother’s age Characteristics o Flat back of head o Small, open mouth o Flat, wide nose o Short neck o Congenital heart deficits o Diminished muscle tone (spierslapte) o Intellectual disability o Dementia Gene for amyloid precursor protein is located on chromosome 21 à extra copy, thus amyloid precursor protein overproduction à higher production of amyloid-b à early + more plaques formation à higher and earlier risk to develop Alzheimer Relevance of diagnosing dementia for people with intellectual disabilities: o To make informed choices and to understand the people with intellectual disabilities Care models Aging-in-place model: individuals remain at home, with supports evolving as dementia progresses In-place progression model: individuals live in specialized dementia-care group homes designed to accommodate stage-specific needs Palliative care: focuses on easing pain and discomfort, reducing stress, and helping people have the highest quality of life possible Hospice care: focuses on quality of life when a cure is no longer possible Behavioral and Psychological Symptoms of Dementia in Down Syndrome scale (BPSD- DS) Is a screening tool for dementia in down syndrome. It focuses on change over time in severity and frequency o Behavior in the last six months vs typical/characteristic behavior before decline occurred Consists of 11 sections: anxious behavior, sleep problems, irritable behavior, obstinate behavior, restless & stereotypic behavior, aggressive behavior,  apathetic behavior, depressive behavior, psychotic behavior, disinhibited behavior and eating and drinking behavior Care burden increased in with dementia most prominently for: o Anxious behavior o Apathetic behavior o Depressive behavior Early changes in anxiousness, apathy, sleep and depressive symptoms, were observed in more than one-third of the questionable dementia group, suggesting these may serve as early alarm signals for Alzheimer Studiegids: Neuropsychologie van Veroudering en Dementie Korte Antwoord Quiz Vraag 1. Wat is het verschil tussen chronologische, biologische en functionele leeftijd? Vraag 2. Beschrijf de twee modellen van veroudering die in de tekst worden genoemd. Vraag 3. Wat is het verschil tussen primaire en secundaire veroudering? Geef een voorbeeld van elk. Vraag 4. Noem drie leeftijdsgerelateerde veranderingen in het brein die worden beschreven in de tekst. Vraag 5. Wat is het verschil tussen de PASA en HAROLD patronen van activatie in de hersenen bij ouderen? Vraag 6. Beschrijf kort drie van de vier cognitieve verouderingstheorieën die worden besproken in de tekst. Vraag 7. Wat zijn de belangrijkste criteria voor milde cognitieve beperking (MCI)? Vraag 8. Wat zijn de belangrijkste pathologische kenmerken van de ziekte van Alzheimer? Vraag 9. Wat zijn de belangrijkste kenmerken van vasculaire dementie in vergelijking met de ziekte van Alzheimer? Vraag 10. Wat zijn de kernsymptomen die kenmerkend zijn voor Lewy-body dementie? Antwoordsleutel Korte Antwoord Quiz Vraag 1. Chronologische leeftijd is de tijd die verstreken is sinds de geboorte, biologische leeftijd is de fysieke staat van het lichaam en de organen, en functionele leeftijd is de competentie van een persoon in het uitvoeren van specifieke taken. Vraag 2. Het selectieve optimalisatie met compensatie model (SOC) stelt dat individuen zich aanpassen door zich te concentreren op sterke punten, het optimaliseren van gedragingen en het compenseren voor verliezen. Het ecologische model stelt dat de interactie tussen iemands competentie en de omgeving leidt tot aanpassing en emotioneel welzijn. Vraag 3. Primaire veroudering is een onvermijdelijk biologisch proces dat alle leden van een soort treft (zoals het grijs worden van haar), terwijl secundaire veroudering wordt veroorzaakt door omgevingsfactoren en levensstijlkeuzes (zoals roken). Vraag 4. Leeftijdsgerelateerde veranderingen in de hersenen zijn onder andere: vermindering van grijze stof in bepaalde gebieden, verlies van witte stof, en een toename van cerebrospinale vloeistof om de ruimte op te vullen. Vraag 5. PASA beschrijft een verschuiving in hersenactivatie van achteren (posterior) naar voren (anterior) bij het ouder worden, terwijl HAROLD een vermindering in asymmetrie van hersenactivatie beschrijft, waarbij beide hersenhelften meer worden gebruikt. Vraag 6. De sensorische deficittheorie stelt dat leeftijd gerelateerde sensorische problemen leiden tot cognitieve achteruitgang. De resource deficittheorie stelt dat de aandacht vermindert met het ouder worden. De snelheid deficittheorie stelt dat cognitieve tekortkomingen komen door een verminderde snelheid van verwerking. De inhibitie deficittheorie stelt dat er een afname is in het vermogen om irrelevante informatie te onderdrukken. Vraag 7. De belangrijkste criteria voor MCI zijn bezorgdheid over de cognitie, beperkingen in een of meer cognitieve domeinen, het behouden van onafhankelijkheid in functionele vaardigheden en de afwezigheid van dementie. Vraag 8. De belangrijkste pathologische kenmerken van de ziekte van Alzheimer zijn de vorming van plaques als gevolg van misvormde beta-amyloïde eiwitten, neurofibrillaire tangles, synaptische verstoring en neurodegeneratie. Vraag 9. Vasculaire dementie heeft vaker een plotselinge start en een stapsgewijze achteruitgang in vergelijking met de ziekte van Alzheimer. Vasculaire dementie wordt vaker gekenmerkt door problemen met aandacht en executieve functies, terwijl geheugenproblemen kenmerkend zijn voor Alzheimer. Vraag 10. De kernsymptomen van Lewy-body dementie zijn fluctuerende cognitie, terugkerende visuele hallucinaties en spontane kenmerken van parkinsonisme. Essay Vragen 1. Bespreek de verschillende theorieën van veroudering, waarbij je zowel biologische als stochastische theorieën belicht. Hoe verhouden deze theorieën zich tot elkaar in het verklaren van het verouderingsproces? 2. Analyseer het concept van cognitieve reserve. Hoe beïnvloedt dit de manier waarop mensen reageren op leeftijdsgerelateerde veranderingen in het brein? 3. Vergelijk en contrasteer de klinische presentaties en onderliggende pathologieën van de ziekte van Alzheimer en vasculaire dementie. Welke factoren dragen bij aan de moeilijkheid van het onderscheiden van deze twee vormen van dementie? 4. Bespreek de verschillende varianten van frontotemporale dementie. Hoe verschillen ze in termen van gedrag, taal en cognitieve symptomen? 5. Beschrijf het concept van mantelzorgerslast en bespreek de risico- en beschermende factoren die van invloed zijn op de mentale gezondheid van mantelzorgers. Woordenlijst Chronologische leeftijd: De leeftijd gemeten in tijdseenheden (maanden of jaren) sinds de geboorte. Biologische leeftijd: De leeftijd van het lichaam gemeten in de staat van organen en fysieke verschijning. Functionele leeftijd: De competentie van een persoon in het uitvoeren van specifieke taken. Derde leeftijd: De periode tussen pensionering en het begin van leeftijd gerelateerde beperkingen. Vierde leeftijd: De periode waarin cognitieve en fysieke beperkingen het dagelijks functioneren belemmeren. Psychologische leeftijd: Hoe goed een persoon zich aanpast aan veranderende omstandigheden. Sociale leeftijd: De maatschappelijke verwachtingen over gedrag en activiteiten van mensen van een bepaalde chronologische leeftijd. Selectieve optimalisatie met compensatie (SOC): Een model van veroudering waarbij individuen zich aanpassen door selectie, optimalisatie en compensatie. Ecologisch model van veroudering: Een model van veroudering waarbij de interactie tussen competentie en omgeving de mate van aanpassing bepaalt. Morbiteit: Ziekte en aandoening. Mortaliteit: Dood. Levensspanne: De maximale leeftijd die een lid van een soort kan bereiken. Levensverwachting: Het gemiddeld aantal jaren dat individuen in een bepaalde geboortecohort naar verwachting zullen leven. Primaire veroudering: Onvermijdelijk biologisch proces dat alle leden van een soort treft. Secundaire veroudering: Veroudering als gevolg van omgevingsfactoren en levensstijl. Geprogrammeerde theorieën: Theorieën die stellen dat veroudering onder genetische controle staat.  Stochastische theorieën: Theorieën die zich richten op willekeurige schade aan vitale systemen tijdens het verouderingsproces. Normatieve veroudering: Wat als een gebruikelijke, normale of gemiddelde uitkomst wordt beschouwd. Succesvolle veroudering: Wat als een ideaal, in plaats van een gemiddelde, uitkomst wordt beschouwd. Positieve veroudering: Het vermogen om geluk en welzijn te vinden, zelfs in het licht van fysieke en/of psychologische uitdagingen. Actieve veroudering: Het proces van het optimaliseren van mogelijkheden voor gezondheid, participatie en veiligheid om de kwaliteit van leven te verbeteren naarmate mensen ouder worden. Compressie van morbiditeit: Stelt dat de meest ernstige gezondheidsproblemen zich concentreren in de laatste levensjaren. Expansie van morbiditeit: Stelt dat het aantal levensjaren in slechte gezondheid toeneemt met een toenemende levensduur. Grijze stof: Hersenweefsel dat voornamelijk bestaat uit neuronale cellichamen. Witte stof: Hersenweefsel dat voornamelijk bestaat uit axonen die door myeline zijn omhuld. Cerebrospinale vloeistof: De vloeistof die de hersenen en het ruggenmerg omringt. Neurotransmitters: Chemische boodschappers in de hersenen. Kristalheldere pragmatiek: Kennis die in het leven is opgebouwd en die stabiel blijft. Vloeibare mechanismen: Controleprocessen die afnemen met het ouder worden. Plasticiteit: Het vermogen van de hersenen om zich aan te passen aan de omgeving. PASA (Posterior-Anterior Shift in Aging): Een patroon van hersenactivatie waarbij ouderen meer activiteit vertonen in frontale gebieden. HAROLD (Hemispheric Asymmetry Reduction in Older Adults): Een patroon van hersenactivatie waarbij ouderen beide hersenhelften meer gebruiken. Sensorische deficittheorie: De theorie dat leeftijdsgerelateerde sensorische problemen leiden tot cognitieve achteruitgang. Resources deficittheorie: De theorie dat veroudering gepaard gaat met een vermindering van de hoeveelheid beschikbare aandachtsbronnen. Snelheid deficittheorie: De theorie dat cognitieve achteruitgang komt door een algemene vermindering van de snelheid van cognitieve processen. Inhibitiedeficittheorie: De theorie dat cognitieve achteruitgang door veroudering komt door een afname van de inhibitie in het werkgeheugen. Scaffolding theorie van veroudering en cognitie: Een theorie die suggereert dat het brein zich aanpast aan uitdagingen door het bouwen van alternatieve hersencircuits. Cognitieve reserve: Individuele verschillen in cognitieve processen die sommige mensen beter in staat stellen om met hersenveranderingen om te gaan. Electieve selectie: Selectie van doelen op basis van voorkeuren en sociale normen.  Verlies-gebaseerde selectie: Een verschuiving in persoonlijke doelen door een verlies van interne of externe bronnen. Neural compensatie: Het proces waarbij individuen met hersenpathologie hersenstructuren gebruiken die normaal gesproken niet worden gebruikt om de schade te compenseren. Dedifferentiatie theorie: De theorie dat de hersenen bij ouderen minder gespecialiseerd zijn en op een bredere range aan inputs reageren. Dementie: Een syndroom gekenmerkt door een progressieve achteruitgang in cognitie. Milde cognitieve beperking (MCI): Een overgangsstadium tussen normale veroudering en dementie. Amnestische MCI: MCI met geheugenstoornissen. Non-amnestische MCI: MCI met stoornissen in andere cognitieve domeinen dan het geheugen. Ziekte van Alzheimer: Een degeneratieve hersenziekte die wordt gekenmerkt door geheugenverlies. Vasculaire dementie: Dementie veroorzaakt door cerebrovasculaire aandoeningen. Witte stof hyperintensiteiten: Schade op micro-niveau, frequent aanwezig bij oudere individuen. Diffuse demyelinisatie: Beschadiging van de myeline in de hersenen. Infarcten: Gebieden van weefselnecrose als gevolg van een gebrek aan bloedtoevoer. Lacunes: Kleine holtes in de subcorticale en diepe structuren van de hersenen. Frontotemporale dementie: Een neurodegeneratieve ziekte die de frontale en/of temporale kwabben selectief treft. Pick lichamen: Inclusies in de neuronen bij mensen met FTD. FTLD-tau: Frontotemporale lobaire degeneratie door tau eiwit inclusies. FTLD-TDP: Frontotemporale lobaire degeneratie door TDP-43 eiwit inclusies. Apathie: Gebrek aan motivatie. Primaire progressieve afasie: Taalstoornis als gevolg van neurodegeneratie in de hersenen. Semantische dementie: Progressief verlies van semantische kennis. Non-fluent primaire progressieve afasie: Taalstoornis gekenmerkt door een moeizame spraak. Logopenische primaire progressieve afasie: Taalstoornis gekenmerkt door moeilijkheden met woord vinden. Lewy-body dementie: Een vorm van dementie met Lewy-lichaampjes in de hersenen. Parkinson’s disease: Een progressieve, neurodegeneratieve ziekte veroorzaakt door de dood van dopaminerge neuronen. Substantia nigra: Een hersengebied dat belangrijk is voor de productie van dopamine. Bradykinesie: Traagheid van beweging. Dementia with Lewy bodies (DLB): Een vorm van dementie met Lewy- lichaampjes.  REM sleep gedragsstoornis: Een aandoening waarbij mensen tijdens de REM slaap acties uitvoeren. Huntington’s disease: Een erfelijke aandoening veroorzaakt door een CAG repeat op chromosoom 4. Chorea: Random, oncontroleerbare bewegingen. Delirium: Een acute verwardheidstoestand. Hyperactief delirium: Een subtype van delirium gekenmerkt door rusteloosheid en agitatie. Hypoactief delirium: Een subtype van delirium gekenmerkt door lethargie en slaperigheid. Anosognosie: Het ontkennen van ziekte. Mantelzorgerlast: De multidimensionale respons op stressoren geassocieerd met de zorgervaring. Wear and tear hypothese: De hypothese dat mantelzorgers geleidelijk achteruitgaan door chronische stress. Adaptatie hypothese: De hypothese dat mantelzorgers zich aanpassen aan de eisen van de zorg en hun gezondheid stabiliseert of verbetert. Trait hypothese: De hypothese dat individuele eigenschappen verklaren waarom sommige mantelzorgers beter functioneren.