Samenvatting_NPD_2025-2026_-_E.T..pdf

# Differential diagnosis of dementia, including depression and frontotemporal dementia ### Core idea * Neuropsychological assessment is a medical procedure with direct implications for patient care and can reveal incidental findings [2](#page=2). * The goals of neuropsychological assessment include contributing to medical diagnosis, evaluating cognitive and emotional functioning, and guiding rehabilitation and return-to-work decisions [3](#page=3). * Hypotheses are formulated based on the referral question, case history, and initial assessment, and then tested using neuropsychological tests [6](#page=6). * Test interpretation involves evaluating both criterion validity (distinguishing between patient groups) and construct validity (measuring the intended cognitive function) [15](#page=15) [17](#page=17). ### Key facts * Neuropsychology studies the relationship between brain function and behavior/behavioral disorders [2](#page=2). * Neuropsychological assessment involves a standardized step-by-step process: referral clarification, dossier review, anamnesis, test administration, and interpretation/reporting [3](#page=3). * When assessing cognitive complaints, it is important to test beyond the reported symptom, as other cognitive domains (e.g., attention) may be the underlying cause [7](#page=7). * No single test is "pure"; tests rely on multiple cognitive functions, necessitating the use of multiple tests to differentiate aspects of a function [7](#page=7). * When interpreting test results, it is crucial to consider the premorbid functioning level of the individual, applying stricter criteria for higher-functioning individuals [11](#page=11). * Reliable Change Index (RCI) can quantify significant changes in test scores over time, accounting for measurement error and reliability [13](#page=13). * In the case of Dhr. Alexander, neuropsychological testing identified deficits in visuospatiële skills, processing speed, and attention, suggesting right hemispheric dysfunction [18](#page=18). * Further medical evaluation, including imaging and blood tests, was recommended for Dhr. Alexander due to cognitive deficits exceeding those expected for a mild traumatic brain injury [19](#page=19). ### Key concepts * **Evidence-Based Practice (EBP):** Emphasized in clinical neuropsychology, with a stronger focus on fixed protocols and rules compared to clinical psychology [2](#page=2). * **Hypothesis Testing:** Neuropsychologists act as scientist-practitioners, formulating and testing hypotheses through structured assessment [4](#page=4). * **Premorbid Functioning:** Estimation of a patient's cognitive abilities before the onset of a disorder, crucial for interpreting test results [11](#page=11). * **Test Battery Construction:** Tests are selected to reveal brain dysfunction while also testing alternative explanations, covering a broad range of cognitive domains [7](#page=7). * **Performance Validity:** Tests used to determine if a patient is exerting maximal effort during assessment, as underperformance can distort results [14](#page=14). * **Criterion Validity:** The ability of a test to distinguish between individuals with and without a specific disorder, often using cut-off scores, sensitivity, and specificity [15](#page=15). * **Construct Validity:** The extent to which a test accurately measures the cognitive function it is intended to measure [17](#page=17). * **Test Profile Interpretation:** Analyzing the pattern of scores across multiple tests and cognitive domains provides a more comprehensive understanding than single test scores [17](#page=17). ### Implications * Neuropsychological assessment results have direct implications for diagnosis, treatment planning, and patient safety (e.g., driving restrictions) [3](#page=3). * The choice of testing approach (psychometric, non-psychometric, or combined) depends on the specific goals of the assessment [8](#page=8). * Redundancy in testing is important; a cognitive function should be assessed with more than one test to avoid relying on a single measure [9](#page=9). * A neuropsychological disorder is defined by a combination of lower-than-expected test scores, a cognitive profile, and patient-specific characteristics, not by isolated test scores [11](#page=11). * The interpretation of test results is the most challenging part of neuropsychological assessment, requiring integration of all gathered information [14](#page=14). --- ## Memory diagnosis * Memory is functionally divided into short-term/working memory (STM/WM) and long-term memory (LTM) [21](#page=21). * STM/WM involves temporary information holding and manipulation, managed by a central executive [22](#page=22). * LTM has a vast capacity for storing consolidated information, accessed through various neural pathways [23](#page=23). * Information typically remains in STM/WM for about 15-20 seconds without active maintenance [21](#page=21). * LTM is categorized into declarative (semantic, episodic) and non-declarative (procedural, priming, conditioning) [21](#page=21). * Consolidation into LTM involves hippocampal and thalamic-cortical routes [23](#page=23). * Retrieval from LTM is strongly guided by the frontal lobes [21](#page=21). * Prospectieve memory, memory for future actions, is crucial for activities of daily living (ADL) [24](#page=24). * Anterograde amnesia is the inability to form new memories, while retrograde amnesia is the loss of old memories [24](#page=24). * **Working memory model (Baddeley):** Comprises a central executive, visuospatial sketchpad, phonological loop, and episodic buffer [22](#page=22). * **Consolidation:** The process by which memories become stable in LTM, facilitated by the hippocampus [23](#page=23). * **Retrieval:** The process of accessing stored information from LTM, primarily directed by frontal areas [23](#page=23). * **Amnestic syndrome:** Characterized by preserved working memory, intellect, and semantic memory, but impaired new information storage [26](#page=26). * **Differential diagnosis:** Differentiating memory deficits often involves assessing verbal vs. non-verbal, simple vs. complex material, and recall vs. recognition [24](#page=24). * Memory assessment should evaluate multiple aspects (verbal, visuospatial, short- vs. long-term) [24](#page=24). * Distinguishing between encoding and retrieval problems is key in differential diagnosis [25](#page=25). * Ecological validity is important; lab tasks should be translated to real-world scenarios [24](#page=24). * Subtle executive deficits can mimic pure memory impairments [24](#page=24). - > **Tip:** Always consider the patient's effort and validity when interpreting memory test results [24](#page=24) - > **Tip:** The distinction between encoding (hippocampal/medial temporal) and retrieval (frontal) issues is crucial for diagnosis [25](#page=25) ### Common pitfalls * Over-reliance on a single memory modality or test [24](#page=24). * Failing to consider the impact of confounding factors like medication, sleep, or substance abuse [25](#page=25). * Not accounting for malingering or suboptimal effort in test performance [34](#page=34). --- * The prefrontal cortex integrates information from posterior cortical areas (emotion, memory, perception) to form a situational understanding [41](#page=41). * This integration allows for concept formation, strategic planning, and modulation of action selection [41](#page=41). * The pathway from posterior to prefrontal cortex to action involves premotor preparation and execution by the primary motor cortex [41](#page=41). * Anterior cingulate cortex monitors errors and performance, providing feedback [41](#page=41). * Myelination proceeds from posterior to anterior, with frontal lobes completing around 20-25 years, impacting adolescent executive control [40](#page=40). * Brodmann areas associated with executive functions include BA46/9 (dorsolateral PFC), BA44/45 (ventrolateral PFC/Broca), BA10 (polar PFC), and BA11 (orbitofrontal) [40](#page=40). * Key white matter tracts connecting to the frontal lobe include the cingulum, uncinate fasciculus, inferior fronto-occipital fasciculus, and arcuate fasciculus [40](#page=40). * Lesions in these tracts can cause disconnection syndromes, mimicking cortical damage [40](#page=40). * 63% of strokes involve frontal lobes, with ~1 in 5 limited to the frontal lobe [44](#page=44). * Frontal lobe tumors often present with mood, behavior, and attention changes [45](#page=45). * **Process-based theory (Petrides & Owen):** Distinguishes between dorsolateral PFC (manipulation/monitoring in working memory) and ventrolateral PFC (maintenance/retrieval in working memory) [42](#page=42). * **Content-based theory (Goldman-Rakic):** Links dorsolateral PFC to spatial ("where") coding and ventrolateral PFC to object identity ("what") coding, analogous to visual pathways [42](#page=42). * **Function-based theory (Stuss):** Categorizes PFC dysfunction into deficient energization (medial PFC), executive disabilities (lateral PFC), impaired self-regulation (ventromedial/orbitofrontal), and disturbed metacognition (polar PFC) [43](#page=43). * The dysexecutive syndrome involves impairments in initiating/sustaining behavior, planning, sequencing, inhibition, flexibility, monitoring, and feedback utilization [46](#page=46). * DSM-5 has replaced "dementia" with "Major Neurocognitive Disorder" and "Mild Neurocognitive Disorder," broadening the diagnostic scope beyond memory [52](#page=52). * Neurocognitive disorders are now classified across six domains: complex attention, executive functions, learning/memory, language, perceptual-motor function, and social cognition [52](#page=52). * Adolescent incomplete frontal myelination can explain risk-taking behavior and weaker executive control [40](#page=40). * Disconnectivity syndromes highlight that functional deficits may arise from pathway damage rather than direct cortical lesions [40](#page=40). * Rehabilitation for dysexecutive syndrome requires addressing anosognosia, disinhibition, and initiation problems through methods like re-education and goal management training [46](#page=46). * The shift to Neurocognitive Disorders in DSM-5 acknowledges that memory is not always the primary deficit in these conditions [52](#page=52). * Early detection of dementia is crucial for better pharmacological outcomes, psychosocial support, and accurate differential diagnosis [55](#page=55). * Alzheimer's disease (AD) is characterized by progressive cognitive and functional decline, with memory often affected first, followed by language and visuospatial issues [56](#page=56) [57](#page=57) [58](#page=58). * Traumatic brain injury (TBI) can cause pseudo-syndromes mimicking psychiatric disorders (psychopathic, depressive, demential) [44](#page=44). * Not all dementia forms start with memory problems, challenging the traditional DSM-IV definition [52](#page=52). --- ### Key facts about Alzheimer's disease pathology (SDAT) * Amyloid plaques are extracellular, insoluble protein deposits that cause inflammation and neuronal loss [59](#page=59). * Neurofibrillary tangles involve the disintegration of intracellular microtubules due to tau protein changes, leading to axonal skeleton loss [59](#page=59). * These changes begin locally in the medial temporal region (hippocampus) and spread outwards [59](#page=59). * Degeneration of the nucleus basalis of Meynert reduces acetylcholine production, impacting memory [59](#page=59). * Lewy bodies are intracellular protein clumps found in cortex or brainstem, core to Lewy body disease [60](#page=60). * Oxidative stress exacerbates neuronal decay in Alzheimer's [60](#page=60). ### Pharmacological treatment of SDAT * No curative treatments exist; interventions can temporarily slow progression [60](#page=60). * Acetylcholinesterase inhibitors (e.g., Donepezil, Rivastigmine, Galantamine) are used in all stages [60](#page=60). * Memantine (NMDA-receptor antagonist) is used in the middle stage [60](#page=60). * Effectiveness varies significantly per individual, with typically modest delays (12-18 months) [60](#page=60). * Common cholinergic side effects include nausea, vomiting, diarrhea, and dizziness [60](#page=60). * Lecanemab, a newer agent for early Alzheimer's, showed statistically significant but clinically small cognitive slowing [60](#page=60) [61](#page=61). * Lecanemab carries risks including infusion reactions and amyloid-related imaging abnormalities (ARIA) [60](#page=60). ### Neuropsychological assessment in SDAT * Screening tests like MMSE (cut-off <24 for mild dementia) and ADAS (ADAS-cog 0-70) are used [61](#page=61). * MoCA can also be used as an alternative [62](#page=62). * These screening tools are considered coarse for early diagnostic protocols [62](#page=62). * MMSE has high AUC for distinguishing Alzheimer's from controls, but weaker for non-amnestic MCI [62](#page=62). * Early cognitive changes in SDAT include normal crystallized intelligence but declining fluid intelligence, mild attention deficits, word-finding problems, visual-spatial issues, and episodic memory loss [62](#page=62) [63](#page=63). * Executive functions like mental flexibility and judgment are often impaired, with frequent anosognosia [63](#page=63). * Emotional and personality changes can occur from the middle stage, making differentiation from depression difficult [63](#page=63). ### Differential diagnosis of dementia * Key differential diagnoses include depression, frontotemporal dementia (FTD), Parkinson's disease dementia, diffuse Lewy body disease, and vascular dementia [64](#page=64). ### Depression and dementia differentiation * In older adults, depression can present with cognitive complaints like memory issues and psychomotor slowness, linked to reduced frontal lobe metabolism [64](#page=64). * Depression is reversible, while dementia is not [64](#page=64). * Cognitive deficits in depression are typically subcortical (slowness, reduced executive function) rather than cortical [64](#page=64). * Memory problems are less pronounced in depression than in Alzheimer's [64](#page=64). ### Frontotemporal dementia (FTD) #### Behavioral variant FTD (bvFTD) #### Language variant FTD (Primary Progressive Aphasia - PPA) #### Motor variant FTD --- ### Parkinson's disease dementia (PDD) * PD is a basal ganglia disorder with motor, cognitive, mood, and behavioral symptoms [81](#page=81). * Caused by reduced dopamine in the substantia nigra due to Lewy bodies [81](#page=81). * Motor symptoms appear when substantia nigra is ~20% of original volume [81](#page=81). * Cognitive issues include executive dysfunction, bradyphrenie (slow thinking), and attention/memory problems [81](#page=81). * Memory issues in PDD: difficulty with retrieval, better recognition than recall; cues help [81](#page=81). * Depression and apathy are common, often secondary to the disease [81](#page=81). * Patients with PDD are typically aware of their condition (not anosognosic) [81](#page=81). * Behavioral changes like disinhibition and hallucinations can occur, the latter often medication-related [81](#page=81). * Cognitive profiles are often lateralized, matching motor symptom onset [82](#page=82). * **Differential Diagnosis:** Motor symptoms prominent in PDD; cognitive issues prominent in SDAT with motor functions intact longer [82](#page=82). ### Diffuse Lewy Body Disease (DLB) * DLB is a clinical syndrome with features of both Alzheimer's (SDAT) and Parkinson's (PD) [82](#page=82). * Pathology involves Lewy bodies in both brain nuclei and cortex [82](#page=82). * Cognitive profile similar to SDAT, with pronounced, fluctuating attention problems and rapid mental clarity shifts [82](#page=82). * Sensory symptoms include initial smell loss; later REM sleep disorders with dream enactment [82](#page=82). * Visual hallucinations are common and strongly visual [82](#page=82). * Parkinson-like motor symptoms (tremor, rigidity, bradykinesia) occur, usually earlier than in Alzheimer's [83](#page=83). * **Critical Clinical Criteria:** Cognitive deficits (attention, fronto-subcortical, visuospatiation) plus at least two of: fluctuating mental status, visual hallucinations, parkinsonian motor symptoms [83](#page=83). * **Differential Diagnosis with SDAT:** DLB has abrupt onset, daily fluctuations, rapid initial progression, motor symptoms; SDAT is gradual, less fluctuating, slower progression [83](#page=83). * **Differential Diagnosis with PDD:** DLB: cognitive decline begins <1 year after motor symptoms; PDD: cognitive decline appears >1 year after motor symptoms [83](#page=83). * **Crucial Warning:** DLB patients are extremely sensitive to neuroleptics, which can be life-threatening [82](#page=82) [83](#page=83). ### Huntington's Disease (HD) * Genetic, autosomal dominant disorder caused by a mutation in the huntingtin gene on chromosome 4 [83](#page=83). * 50% chance of inheritance from an affected parent [83](#page=83). * Onset typically around age 40, with an average life expectancy of 15 years post-onset [83](#page=83). * **Clinical Criteria:** Involuntary movements (chorea, dystonia), cognitive decline, emotional/behavioral changes [84](#page=84). * Cognitive symptoms include psychomotor slowness, executive dysfunction (perseveration, poor ADL organization), and memory problems [84](#page=84). ### Vascular Disorders --- * Differential diagnosis of dementia involves distinguishing it from other conditions with overlapping symptoms, particularly depression and frontotemporal dementia (FTD). [97-115 * Understanding language, speech, pragmatics, and attention disorders is crucial for accurate diagnosis. [97-114 * Language disorders can be acquired (aphasia) or developmental (dysphasia) [99](#page=99). * Aphasia typically results from acute lesions like stroke (CVA) or trauma, with recovery most significant in the early weeks [99](#page=99). * Progressive aphasia is associated with neurodegenerative conditions like PPA, Alzheimer's, or tumors [99](#page=99). * The WADA test, historically used for pre-operative language dominance assessment, is now largely replaced by fMRI and TMS . * Language assessment in neurosurgery involves pre-operative profiling, intra-operative stimulation, and post-operative follow-up . * Screening tools like ABC, ScreeLing, MMSE, ACE-R, and OCS-NL help detect language and cognitive issues . * Specific diagnostic instruments for word finding include the Boston Naming Task (BNT) and the Dutch Naming Task (NBT) . * Comprehensive test batteries like PALPA, AAT, and CAT-NL analyze various language processing subcomponents . * Tests at the activity and participation level, like the ANTAT, assess daily functional communication . * Attention is a complex process involving focus, filtering, alertness, and regulation, often described by patients as memory or processing speed issues . * **Dysarthria** refers to articulation difficulties, distinct from language problems [97](#page=97). * **Apraxia of speech** involves difficulties with speech planning and motor sequencing [97](#page=97). * **Pragmatics** relates to the contextual use of language and social communication, often impaired in right hemisphere disorders [98](#page=98). * **Aprosodia** is a disorder of speech prosody (intonation, rhythm), affecting reception or expression [98](#page=98). * **Cognitive Communication Disorder** encompasses problems with pragmatic language use and social interaction [98](#page=98). * **Aphasia subtypes** (Broca, Wernicke, Global, Conduction, Anomic, Transcortical) are classified based on lesion location and symptom profiles. [104-109 * **Subcortical aphasias** (thalamic, striato-capsular, cerebellar) and **pure language disorders** (pure alexia, verbal agnosia) represent less common presentations . * **Diagnostic approaches** range from initial screening to in-depth test batteries, focusing on disorder, activity, and participation levels. [110-114 * **Functional communication** and **compensatory strategies** are increasingly important goals in therapy . * **Attention deficits** are often presented by patients as memory, processing speed, or overstimulation complaints . * Accurate diagnosis of language and communication disorders is essential for targeted rehabilitation . * Understanding lesion topology helps predict specific language deficits [97](#page=97). * Neuropsychological assessment is crucial for understanding the impact of neurological conditions on communication . --- ## Attention: Diagnosis and Assessment * Attention problems are common across various neurological and psychiatric conditions, including neurodegenerative diseases and mood disorders . * Understanding attention is crucial within broader information processing models . * Diagnostic assessment involves a structured process including anamnesis, neuropsychological testing, and observations . * Attention is divided into intensity (arousal, sustained attention) and selectivity (focused, divided attention) . * Arousal is the basic alertness level, with tonic (sustained) and phasic (short-term) components . * Sustained attention refers to the ability to maintain focus over time, declining with fatigue . * Focused attention acts as a filter, suppressing irrelevant information, often visualized as a flashlight beam . * Divided attention involves monitoring multiple information sources simultaneously . * Neuroanatomically, arousal involves the Ascending Reticular Activating System (ARAS) . * Focused attention involves the amygdala (value assignment), thalamus (filtering), colliculi superior (eye movements), and frontal eye fields (FEF) (conscious control) . * Divided attention relies heavily on the parietal cortex for orienting and integrating spatial information . * Attention control, an executive function, is driven by the prefrontal cortex (PFC) . * Broadbent's model proposed a bottleneck filter between short-term and long-term memory, later refined by acknowledging the "cocktail party phenomenon" where relevant stimuli can still penetrate . * Shiffrin and Schneider's model differentiates between automatic and controlled processing, with attention being essential for the latter . * Information processing speed is a sensitive indicator of cognitive function, with slower speeds impacting attention and leading to overload . * Attention span is the duration of focused concentration and is influenced by individual, emotional, and situational factors . * When assessing attention, family or environment members are often more reliable informants than the patient regarding changes from baseline functioning . * Neuropsychological tests assess different attention domains, with test selection depending on the patient's functioning level . * Ecological validity is enhanced by tests that mimic everyday tasks, increasing patient recognition and relevance . * Implicit access to information can occur in neglect, where stimuli are processed unconsciously and can influence behavior even if not consciously reported . * Impaired attention can lead to overstimulation and social withdrawal . * Arousal fluctuations can mimic attention disorders, and high arousal can lead to errors . * In guiding patients with PFC lesions, information should be broken down into smaller chunks with sufficient breaks . * Neuropsychological testing requires careful selection of tests, with more difficult tasks used for high-functioning individuals to reveal subtle deficits . * Observations during testing can reveal underlying issues, such as distraction impacting selective attention or executive difficulties leading to inefficient search strategies . --- ## Neglect: associated disorders and neuroanatomy ### Associated disorders * Anosognosie: Lack of awareness of neglect . * Anosodiaforie: Awareness of neglect but indifference to its consequences . * Hemisomatoagnosie: Unawareness of the existence of a contralesional body half . * Hemisomatoparafrenie: Awareness of body but denial of ownership of contralesional parts . * Hemimisoplegie: Aggression towards paralyzed or neglected body parts . * Allokinesie: Movement of the wrong body half in response to a command . * Tactile allochiria/alloesthesia: Tactile stimulation on one side is perceived on the other . * Visual allochiria: Visual stimuli are perceived on the incorrect side . * Mirror agnosia: Inability to recognize mirror images as reflections . * Mirror ataxia: Reaching for the mirror image instead of the actual object . * Associated non-spatial attention problems include delayed arousal, reduced processing speed, and difficulties with sustained/selective attention . * Executive function deficits include inefficient search strategies, perseveration, reduced inhibition, and working memory problems . ### Neuroanatomy of neglect * Neglect is typically caused by lesions in the middle cerebral artery territory . * Symptoms can be multimodal: visual, auditory, tactile, gustatory, or motor . * **Posner's model of attention shifts:** * Disengage: Posterior parietal cortex . * Move: Superior colliculus (reflexive saccades) . * Engage: Pulvinar nuclei of the thalamus . * The parietal cortex, especially around the intraparietal sulcus, is crucial for the 'disengage' aspect of attention . * The hemispatial theory posits that the right hemisphere is dominant for spatial processing, processing both left and right space, while the left hemisphere primarily processes the right side . * Right hemisphere lesions have a greater impact, leading to neglect more frequently than left hemisphere lesions . * Spatial attention relies on a distributed network, including parietal and temporal lobes, pulvinar, thalamus, superior colliculus, and frontal eye fields . * Functional imaging can reveal hypoperfusion in areas critical for attention, which may not always correlate with structural lesions . ### Neglect: three dimensions * Neglect can be classified by processing stage (sensory, motor, representational), spatial frame (personal, peripersonal, extrapersonal), and reference frame (egocentric, allocentric) . * **Sensory neglect:** Affects detection and localization (visual, auditory, tactile, olfactory, gustatory) . ### Neglect: diagnostics --- ### Auditieve agnosie * Inability to recognize auditory information (verbal and non-verbal) despite intact hearing . * **Cortical/cerebral deafness:** Inability to recognize speech and environmental sounds; temporal and spatial discrimination may be impaired . * **Pure word deafness:** Inability to understand and repeat spoken language, but reading, writing, and speaking remain intact . * **Auditory sound agnosia:** Inability to recognize environmental sounds while speech comprehension is preserved . * **Amusia:** Inability to recognize, appreciate, interpret, or reproduce musical tones/rhythms . * **Paralinguistic agnosias:** Includes aprosodia (inability to recognize/produce emotional tone in language) and phonagnosia (inability to recognize familiar voices) . * Diagnosis often relies on observation and excluding hearing disorders; referral to an audiologist is common . ### Tactiele agnosie * Disorders in processing tactile information, with intact tactile sensitivity but impaired recognition . * **Astereognosis:** Inability to recognize objects by touch alone . * Testing involves blindfolding and testing each hand separately, typically assessing the contralesional hand . ### Reukagnosie * Inability to recognize familiar smells while the sense of smell is intact; very rare . * Often occurs with prosopagnosia; typically results from lesions in the right inferior temporal cortex . ### Visuele agnosie * Inability to recognize or name images, colors, objects, or people after visual presentation; other sensory modalities remain intact . * **Apperceptive agnosia:** Problem in early visual processing; objects and shapes are not recognized, copying is poor . * **Associative agnosia:** Problem in higher-level visual processing; simple object recognition and naming are intact, but spontaneous meaning retrieval is impaired . * **Objectagnosie:** Inability to recognize visually presented objects . * **Prosopagnosie:** Inability to recognize familiar faces, including one's own . * **Kleuragnosie:** Inability to recognize, name, or categorize colors . * **Simultaanagnosie:** Inability to perceive multiple objects or parts simultaneously; seeing elements but not the whole . * **Syndroom van Bálint:** Combination of simultaanagnosie, oculomotor apraxia, and optic ataxia . ### Stoornissen in de perceptie van het lichaamsschema * Problems in recognizing, localizing, and naming body parts; not due to primary sensory deficits but disturbed body schema representation . * **Vingermislokalisatie:** Inaccurate identification of touched fingers . * **Vingeragnosie:** Inability to visually recognize, move, localize, or identify fingers . * **Autotopagnosie:** Inability to recognize, locate, and identify parts of one's own or others' bodies . * **Links-rechtsverwarring:** Inability to distinguish left and right sides of the body . --- ### Ideokinetic and ideational apraxia * **Ideokinetic/motor apraxia:** Inability to correctly execute a motor command despite recognizing the object and understanding the intent. The patient forgets *how* to perform the movement . - **Ideational apraxia:** Inability to construct a plan or idea for a specific movement; the patient recognizes the object but doesn't know what to do with it. This is a problem * **Liepmann's model:** * Movement formula: A spatiotemporal visual image of the intended action, produced by the cerebral cortex (especially posterior cortex) . * Execution steps: 1. Activate formula, 2. Transfer formula to sensomotorium, 3. Execute via motor/somatosensory cortex . * Disorders: Sensorimotor issues → limb-kinetic apraxia; Transfer problems → ideokinetic/ideomotor apraxia; Formula problems → ideational apraxia [1](#page=1) [2](#page=2) [3](#page=3). ### Lateralization and apraxia classification * Praxis is primarily a left-hemisphere function, with the left sensomotorium controlling the right hand . * Apraxia is usually bilateral, even with unilateral left hemisphere lesions, but rare lesions in connecting structures can cause left-hand-only apraxia . * **Terminological confusion exists:** Authors may use "ideomotor" where others mean "ideational" . * Apraxia can be categorized by functional deficit (e.g., ideational), location (e.g., limb apraxia), or prominent symptom (e.g., dressing apraxia) . ### Clinical facts and myths about apraxia * Most common causes of apraxia are stroke and dementia . * Post-left CVA, 30-50% have ideomotor apraxia of the left hand; post-right CVA, it's ~5% . * Apraxia often masks in right hemiplegia due to forced use of the left hand . * **Myth:** Apraxia recovers spontaneously and quickly after stroke (False). 50% remain apraxic 5-23 months post-stroke . * **Myth:** Apraxia's impact on daily life is mild (False). It severely interferes with ADL and independence . ### Current models of apraxia * **Anatomical model:** Praxis network is left-lateralized, involving posterior temporal, inferior/superior parietal lobules, premotor, and primary motor cortex . * Route 4 (connecting parietal to premotor/motor areas) is crucial for transferring movement formulas. Damage causes ideomotor/ideokinetic apraxia . * **Cognitive model:** Apraxia as an information processing disorder . * Input processed in sensorimotor-perceptual system. * Transfers to conceptual system (action knowledge, object knowledge). * Response selection, then production system (motor program selection/execution) . * Defects in conceptual system → ideational apraxia; transition → ideomotor apraxia; motor output system → limb-kinetic apraxia . ### Assessment of apraxia * Assessment is complex due to potential influence of aphasia and motor deficits . * Common tasks include pantomiming intransitive/transitive gestures, imitation, and actual object use . * Imitation offers the movement formula (copying), while pantomiming requires recalling it from the conceptual system . ### Neural activation during object-related praxis tasks ### Ventral and dorsal visual cognition streams ### Alternative explanations for tool use ### Motor affordances ### Action observation and motor resonance ### Mirror neuron system and motor imagery ### Treatment of apraxia ### Brain lateralization --- ## Neuropsychopharmacology: Implications for Cognitive Function ### Antipsychotics * **Conventional antipsychotics** are D₂-dopamine receptor antagonists, blocking postsynaptic receptors . * **Indications:** Acute psychotic episodes, relapse prevention, suppression of manic excitement . * **Effectiveness:** More effective for positive than negative symptoms of psychosis . * **Adverse effects:** Extrapiramidal symptoms (e.g., shuffling gait, small steps) are common, especially from nigrostriatal pathway blockade . * **Atypical antipsychotics** (e.g., clozapine, risperidone) block both dopamine and serotonin receptors . * **Atypical indications:** Similar to conventional, but also beneficial for negative symptoms . * **Atypical adverse effects:** Fewer extrapiramidal symptoms, but sedation, hypersalivation, and potential blood dyscrasias requiring monitoring . ### Antidepressants * **Mechanism:** Inhibit monoamine breakdown or reuptake, increasing serotonin and noradrenaline availability . * **Monoamine oxidase inhibitors (MAOIs):** Inhibit monoamine breakdown; not first-line due to side effects like blood pressure fluctuations . * **Monoamine uptake inhibitors (MUIs):** * **Tricyclic antidepressants (TCAs):** Inhibit noradrenaline and serotonin reuptake; anticholinergic and sedative side effects impact cognition and memory . * **Selective serotonin reuptake inhibitors (SSRIs):** Fewer side effects, safe in overdose, minimal cognitive impact; used for anxiety and OCD . * **Selective noradrenaline reuptake inhibitors (NARIs) & Serotonin-noradrenaline reuptake inhibitors (SNRIs):** Increase alertness by potentiating noradrenaline . * **Lithium:** Affects monoaminergic transmission; has a very small therapeutic window requiring frequent serum monitoring . * **Lithium indications:** First-line for bipolar disorder, augmentation for refractory depression . * **Lithium side effects:** Therapeutic doses: thirst, polyuria, mild tremor, memory issues. Overdose: vomiting, diarrhea, severe tremor, cognitive disturbances . ### Anxiolytics and Hypnotics * **Benzodiazepines** (e.g., lorazepam, diazepam) enhance GABA transmission . * **GABA:** The primary inhibitory neurotransmitter in the brain, causing a general dampening effect . * **Indications:** Generalized anxiety, sleep problems . * **Adverse effects:** Sedation, psychomotor slowing, delayed information processing; dysarthria and ataxia at high doses. Relatively safe in overdose . ### Anti-epileptics * **Mechanism:** Suppress neuronal excitability by enhancing inhibition or suppressing excitation . * **Common drugs:** Carbamazepine, phenytoin, valproate, lamotrigine . * **Adverse effects:** All have a sedating effect, causing psychomotor slowing and delayed information processing. Valproate and carbamazepine can have negative cognitive effects even at therapeutic doses . ### Anti-Parkinsonian Agents * **Goal:** Compensate for dopamine deficiency and restore dopaminergic/cholinergic balance in basal ganglia . * **L-dopa:** A dopamine precursor that crosses the blood-brain barrier . ### Psychostimulants ### Alzheimer's Medication --- ## Common mistakes to avoid - Review all topics thoroughly before exams - Pay attention to formulas and key definitions - Practice with examples provided in each section - Don't memorize without understanding the underlying concepts

| Term | Definition | |------|------------| | Neuropsychology | The study of behavior and behavioral disorders in relation to disorders of brain function, focusing on the relationship between the brain and behavior. | | Neuropsychological Assessment (NPO) | A diagnostic act that involves evaluating behavior and cognitive functions to identify and link behavioral disorders to brain dysfunction, with results having direct implications for patient treatment and potentially revealing underlying cerebral issues. | | Differential Diagnosis | The process of identifying a condition from a set of similar conditions based on a comparison of symptoms and signs, often involving multidisciplinary input. | | Heteroanamnesis | The process of gathering information about a patient's complaints and their course and severity from individuals in the patient's immediate environment, rather than from the patient directly. | | Premorbid Intellectual Functioning | An estimation of a patient's cognitive abilities and intellectual level prior to the onset of any neurological or psychiatric disorder. | | Traumatic Brain Injury (TBI) | Damage to the brain caused by an external force, which can lead to a range of cognitive, physical, and emotional impairments. | | Subdural Hematoma | A collection of blood between the dura mater and the arachnoid mater, typically resulting from venous bleeding and often developing gradually. | | Epidural Hematoma | A collection of blood between the dura mater and the skull, usually caused by arterial bleeding and characterized by rapid onset and life-threatening consequences. | | Cerebrovascular Accident (CVA) | Also known as a stroke, this occurs due to a disruption of blood flow to the brain, either by a blockage (ischemic stroke) or rupture (hemorrhagic stroke) of a blood vessel. | | Dementia | A chronic or persistent syndrome characterized by a decline in cognitive function severe enough to interfere with daily life, affecting memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgment. | | Depression | A mood disorder characterized by persistent sadness, loss of interest or pleasure, and a range of emotional and physical problems that can affect how a person feels, thinks, and behaves. | | Frontotemporal Dementia (FTD) | A group of brain disorders caused by progressive nerve cell loss in the frontal and temporal lobes of the brain, affecting behavior, personality, and language. |