NDD V5.1

[Audio] Neuro-Degenerative Disorders: Causes, Presentation & Management Presented by Shripuja S Mphil II Clinical Psychology Trainee 2022 spmphil2@gmail.com Seminar Presentation 1.

[Audio] Index • Introduction • Etiology • Disorders • Neuro-Psychological Assessments • Neuro-Psychotherapy • Case studies • Management plan • References 2.

[Audio] Introduction Definition Neuro-degeneration refers to a progressive structural and functional loss of neurons causing heterogeneous clinical and pathological expressions followed by deterioration of functional anatomy These can be differentiated based on their different pathological mechanistic pathways This progressive neuronal cell death often leads to various neurodegenerative disorders ( NDDs) like Parkinson's disease ( PD) Primary Progressive Aphasia Progressive supranuclear palsy ( PSP) Alzheimer's disease ( AD) Dementia with Lewy Bodies ( DLB) Multiple System Atrophy ( MSA) Corticobasal Syndrome Amyotrophic lateral sclerosis ( ALS) 3.

[Audio] Etiology Factors SocioCultural Biological Genetic 4.

[Audio] Genetics of neurodegenerative diseases: an overview ( Lasse Pihlstrom et al, 2017) Genetics of neurodegenerative diseases • Genetic factors are central to the etiology of neuro degeneration. • Both as monogenic causes of heritable disease and as modifiers of susceptibility to complex, sporadic disorders. an overview • Genetics plays an essential role in translational research, ultimately aiming to develop novel disease-modifying therapies for neurodegenerative disorders. (Lasse Pihlstrom et al,2017 • It is anticipated that the individual genetic profiling will also be increasingly relevant in a clinical context, with implications for patient care in line with the proposed ideal of personalized medicine. 5.

[Audio] The severity and course of dementia can be affected by psychosocial factors. The higher a person's premorbid intelligence and education, the better they can compensate for intellectual deficits. People who have a rapid onset of dementia use fewer defenses than do those who experience an insidious onset. Anxiety and depression can intensify and aggravate the symptoms. Psycho-Social Factors ( kaplan & Sadock's, 2016) 6.

[Audio] Biological Factors A Neurodegenerative Disease is a condition that affects neurons in the brain, causing symptoms such as memory loss, moodiness, anxiety, depression, and agitation. Treatment for each neurodegenerative disease varies Consulting experts in the field with specialized training is necessary to ensure the correct diagnosis. 7.

[Audio] Personality traits and risk of cognitive impairment and dementia ( Antonio Terracciano et al, 2017) • Here they investigated the association between five factor model personality traits • ( neuroticism, extraversion, openness, agreeableness, and conscientiousness) and • Participants from the Health and Retirement Study (N> 10,000) completed a personality scale in 2006– 2008 and their cognitive status was tracked for up to 8 years using the modified Telephone Interview for Cognitive Status ( TICSm). • Adjusting for age, sex, education, race, and ethnicity, lower conscientiousness and agreeableness and higher neuroticism were independently associated with increased risk of dementia. • These associations remained significant after adjusting for other risk factors for dementia, including income, wealth, smoking, physical inactivity, obesity, diabetes, hypertension, and blood biomarkers. • They found robust evidence that personality is associated with risk of cognitive impairment and dementia in a large national sample. 8.

[Audio] Personality and Alzheimer's disease: An integrative review Personality change in individuals with dementia from 9 studies summarized by Robins Wahlin and Byrne ( 2011) 9.

[Audio] NDD Terminology Dementia It refers to a broad category of neurodegenerative diseases. However, not all causes of dementia are degenerative. For example, a single stroke may result in cognitive difficulties, but the symptoms remain largely stable over time and do not progress. Most commonly, the term is used in context with progressive neurodegenerative disease. Memory disorder Several conditions that can affect memory. These disorders may also affect language, decision making, attention, and visual perception. Alheimer's disease is most familiar NDD, or " memory disorder." Mild cognitive impairment ( MCI) Cognitive change but with no decline in daily function. The individual and others around them may notice subtle change. 10.

[Audio] Normal age-relatedcognitive changes: The mind and brain change as we age. •Slower thought process •Taking longer to learn something new •Decreased ability to multitask •Occasional temporary difficulty remembering a word or name •Occasional misplacing an item such as glasses or keys •Occasionally walking into a room and forgetting why Typical cognitive changes include • Warning signs that cognitive changes may be more serious than those caused by normal aging: difficulty in retrieving information from memory. •An individual may forget that a conversation occurred and have difficulty managing finances. •These types of cognitive changes indicate that an individual should consult with an expert for a comprehensive evaluation. Warning signs • A disease state at a microscopic and cellular level that is not yet observable with MRI scans or neuropsychological testing. • The term has become increasingly important as the disease processes of many neurodegenerative diseases become better understood. Understanding the prodromal state is increasingly useful in understanding disease intervention. Prodormal Neurodegenerative disease 11.

[Audio] Causes • Most NDDs begin years or decades before symptoms are present. • Research shows that, in every neurodegenerative disease, there is an abnormal protein involved which becomes toxic to the nerve cells, resulting in cell death and cognitive decline. • As the disease progresses, additional nerve cells can become over-stimulated and die as well. • Furthermore, with cell death, inflammation ensues, causing further cell death. Ultimately many factors contribute to disease progression in its later stages. Proteins involved in neurodegenerative diseases: Beta-amyloid –A major protein involved in Alzheimer's disease, but can also be present in Dementia with Lewy Bodies Tau – Along with beta-amyloid it comprises Alzheimer's disease pathology. However, it is can also be present in other NDDs. Synuclein– A protein commonly seen in Parkinson's disease (with or without cognitive changes), Dementia with Lewy Bodies and Multiple System Atrophy TDP- 43 – Present in Amyotrophic Lateral Sclerosis ( ALS), types of FrontotemporalLobar Degeneration, HippocampalSclerosis (progressive scarring of hippocampus) Huntington – A mutated protein present in Huntington's disease PrP – Primary protein in Creutzfeldt-Jakob disease ( CJD) 12.

[Audio] Risk Factors Several conditions increase the risk for developing future NDDs, including: • Cardiovascular disease • Cerebrovascular disease • Smoking • Prior head injury (ranging from concussion to severe brain damage) • Age • Genetics • Diet • Sleep deprivation • Alcohol use • Depression • Poor fitness • High blood pressure • Uncontrolled diabetes 13.

[Audio] While a cure to most NDDs remains elusive, strategies can be taken to slow down symptom progression and provide higher quality of life. In addition, for patients with MCI, TranscranialMagnetic Stimulation ( TMS) may turn back time on symptoms by up to two years. •A through and detailed timeline of symptoms and their progression. •Cognitive testing is used to evaluate for cognitive changes. More involved testing is required in the form of formal neuropsychological testing, which evaluates each cognitive area in detail. • MRI is a evaluation for diseases of the central nervous system and will allow the physician to evaluate for strokes, bleeding, tumors and brain shrinkage. Diagnosis • At present there are no drugs that can alter the underlying disease state. • Just as medication will only alleviate the symptoms of arthritis for a period of time, the available medications can simply delay symptom progression for a period. • However, many lifestyle factors can be enhanced to stave off symptoms and increase quality of life. Treatments 14.

[Audio] Neuro-Degenerative Disorders - An overview 15.

[Audio] Late-Onset Alzheimer's disease ( AD) • Above 65 years • prototypical memory disease, most commonly presenting with short term memory loss. Caused by abnormal accumulation of beta-amyloid and tau proteins in the brain. Young-Onset Alzheimer's disease/Early-Onset Alzheimer's disease (AD) • 65 and younger • include delusional thoughts ( paranoia, false beliefs), difficulty with decision making and using judgment, and language difficulty. Fronto-temporal lobar degeneration • common type of dementia in 40- 50 year-old • Common symptoms include changes in food preferences toward sweets and overeating, impaired judgment, lack of empathy, apathy, repetitive complex rituals, and loss of socially appropriate behavior. 16.

[Audio] Primary Progressive Aphasia • A primary disorder of language • Common symptoms include prominent and frequent difficulty finding the correct words, pauses in speech, and difficulty naming objects. Posterior Cortical Atrophy • It is a disorder of visual perception and processing. • It often begins with subtle symptoms of difficulty reading, navigating, recognizing objects and faces, and bumping into objects. Parkinson's disease and Parkinson's disease dementia • a primary movement disorder with progressive difficulty with movement and walking. • Common cognitive changes include slowness of thought, difficulty concentrating, memory difficulties, delusions, hallucinations, and impaired judgment. 17.

[Audio] Dementia with Lewy Bodies ( DLB) • " Parkinson's plus syndromes" • Recurring visual hallucinations can be seen early in the disease which are very vivid and commonly consist of people or small animals. Progressive Supranuclear Palsy ( PSP) • Characteristic symptoms include falls early in the course of the disease, difficulty walking, and shuffling. Multiple system atrophy ( MSA) • prominent symptoms of autonomic nervous system dysfunction such as slow or fast heart rate, position-dependent drop in blood pressure, urinary difficulties, erectile dysfunction, and breathing difficulties while sleeping, with a high pitched wheezing sound during inspiration. 18.

[Audio] Vascular cognitive impairment •It is not progressive in the same sense as a neurodegenerative disease, vascular damage is irreversible. •The progression of vascular disease can be slowed down by treating vascular risk factors such as diabetes, high cholesterol, and high blood pressure. Corticobasal syndrome •The syndrome typically presents with loss of dexterity and clumsiness in the hands. •Cognitive impairment is a prominent part of the CBS and commonly includes language impairment and behavioral changes, though various other impairments may be seen as well. Creutzfeldt-Jakob disease •It is with life-expectancy less than 1 year and often only a few months. (also known as mad cow disease) •Common symptoms are clumsiness, abnormal movement of the arms and legs, loss of balance, and slurred speech. 19.

[Audio] Neuro-Psychological Assessments 20. . . Neuro-Psychological.

[Audio] Neuropsychologic Tests • These tests usually have standardized normative information available for comparison with healthy people in the same age range, often stratified by sex, education, and occasionally race. • By performing a comprehensive battery of tests, usually with several tests in each domain ( Table), neuropsychologists establish a profile of strengths and weaknesses, which are considered the cognitive " phenotype," and helps narrow the differential diagnosis. • Multiple other pieces of information are integrated, including mood and behavior symptoms, medications, medical comorbidities, family history, medical history, and mitigating factors that may affect testing. • These data, collected during the record review and interview, are taken into account in test data interpretation and contribute to the overall characterization of an individual's neurobehavioral status. 21.

[Audio] Mini-Mental Status Examination 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. To estimate the severity and progression of cognitive impairment. To follow the course of cognitive changes in an individual over time; thus making it an effective way to document an individual's response to treatment. It examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orienttion. It has both validity and reliability for the diagnosis and longitudinal neuro-assessment. 22.

[Audio] Category Possible points Description Orientation to time 5 From broadest to most narrow. Orientation to time has been correlated with future decline. Orientation to place 5 From broadest to most narrow. This is sometimes narrowed down to streets, and sometimes to floor. Registration 3 Repeating named prompts Attention and calculation 5 Serial seven or spelling " world" backwards. It has been suggested that serial sevens may be more appropriate in a population where English is not the first language. Recall 3 Registration recall Language 2 Naming a pencil and a watch Repetition 1 Speaking back a phrase Complex commands 6 Varies. Can involve drawing figure shown. Mini-Mental Status Examination 23.

[Audio] PGI BATTERY OF BRAIN DYSFUNCTION ( PGIBBD) ( D. Pershad et al 1990, 2007) It is a sophisticated collection of various tests that are used to quantify cognitive dysfunction, impairment, decline, or deficits in clinical settings. The P.G.I Battery of Brain Dysfunction measures well-known cognitive functions of the brain behaviour such as intelligence (both performance and verbal), memory, perceptual acuity, and transference from one hemisphere to another. This battery includes five tests : Bhatia's Short Scale, Verbal Adult Intelligence Scale, PGI Memory Scale, Bender Visual Motor Gestalt Test and, Nahor Benson Test of Perceptual Acuity. 24.

[Audio] Nimhans Neuro-battery • NIMHANS Neuropsychological Battery for Elderly • ( NNB-E) has been developed and standardized on Indian population. • NNB-E is a comprehensive battery developed for assessing cognitive functions in Indian older adults. • It is a brief battery that takes 60 min to administer consists of measures of attention memory executive functions language visuo-spatial construction parietal focal signs 25.

[Audio] Tests included in the battery are Word List Story Recall Test ( memory of logical passage) Stick Construction Test for visuo-spatial construction with immediate and delayed recall for visual memory Digit Span Corsi block-tapping test ( working memory) Category fluency Go/No-Go Picture cancellation for sustained attention Parietal focal signs ( agnosia/ apraxia/ body schema disturbances/left right disorientation/ acalcuil a). 26.

[Audio] ABBREVIATED MENTAL TEST Questions 10-point test It is used for rapidly assessing elderly patients for the possibility of dementia. It is also used to assess for mental confusions and other cognitive impairments. What is your age? (1 point) What is the time to the nearest hour? (1 point) Give the patient an address, and ask him or her to repeat it at the end of the test. (1 point)e.g. 42 West Street What is the year? ( 1 point) What is the name of this place (e.g. hospital) (1 point) Can the patient recognize two persons (the doctor, nurse, home help, etc.)? (1 point) What is your date of birth? (day and month sufficient) (1 point) In what year did World War 2 end? (1 point)(other dates can be used, with a preference for dates some time in the past.) Name the current President/ Prime Minister/ Monarch. (1 point) Count backwards from 20 down to 1. (1 point) 27.

[Audio] Clinical Dementia Rating scale [ Morriss, 1993] - it allows more reliable staging of dementia than MMSE - it is based on caregiver accounts of problems in daily functional and cognitive tasks. 28.

[Audio] Case studies 29. . . Case studies. 29.

[Audio] Case of Mr. J • Mr. J, a 70-year-old retired businessman, was brought to psychiatric services on referral by the family physician. • His wife claimed that Mr. J had become so forgetful that she was afraid to leave him alone, even at home. • Mr. J retired at age 62 years after experiencing a decline in work performance during the previous 5 years. • He also slowly gave up hobbies he once enjoyed ( photography, reading, golf) and became increasingly quiet. • However, his growing forgetfulness went unnoticed at home. • Then one day, while walking in an area he knew well, he could not find his way home. • From then on, his memory failure began to increase. • He would forget appointments, misplace things, and lose his way around the neighborhood he resided in for 40 years. • He failed to recognize people, even those he knew for many years. • His wife had to start bathing and dressing him because he forgot how to do so himself. • On examination, Mr. J could not recall the time or place. He was only able to recall his name and place of birth. • Mr. J seemed lost during the interview, only responding to questions with an occasional shrug of his shoulders. • When asked to name objects or to recall words or numbers, Mr. J appeared tense and distressed. • Mr. J had difficulty following instructions and was unable to dress or undress. • His general medical condition was good. Laboratory examinations showed abnormalities on Mr. J's EEG and CT scans. 30.

[Audio] Case of Mr. M • Mr. M, 77 years of age, came for a neurologic examination because he noticed his memory was slipping, and he was having difficulty concentrating, which interfered with his work. • He complained of slowness and losing his train of thought. • His wife stated that he was becoming withdrawn and was more reluctant to participate in activities he usually enjoyed. • He denied symptoms of depression other than feeling mildly depressed about his disabilities. • Two years prior, Mr. M developed an intermittent resting tremor in his right hand and a shuffling gait. • Although a psychiatrist considered a diagnosis of Parkinson disease, the neurologist did not confirm it. • During an initial neurologic examination, Mr. M's spontaneous speech was hesitantand unclear ( dysarthric). • Cranial nerve examination was normal. • Motor tone was increased slightly in the neck and all limbs. • He performed alternating movements in his hands slowly. • He had a slight intermittent tremor of his right arm at rest. • Reflexes were symmetrical. • Three weeks later, the patient had a neuropsychologicexamination. • On the examination, Mr. M had impairment of memory, naming, and constructional abilities. 31.

[Audio] Case of Mrs. S • Mrs. S, 75 years of age, was brought to the emergency department after being found wandering her neighborhood in a confused and disoriented state. • She was in good health until a few months before, when her husband had minor surgery, requiring 10-day hospitalization. • About a month after her husband returned home, he and their two adult children, who do not reside with them, reported a noticeable change in Mrs. S's mental status. • Mrs. S became hyperactive and appeared to have excessive energy, was agitated and irritable, and had difficulty sleeping at night. At the examination, Mrs. S was disoriented to time and place, agitated, and confused. • Her husband revealed upon an interview that Mrs. S has for many years suffered from dizziness and light-headednessupon standingand occasionally suffered from falls, none of which caused any significant damage. • Not long before her confused symptoms began, Mrs. S had suffered a fall one night, and her husband found her the next morning lying next to the bed in a confused state. • Because of her history of falls, neither Mr. S nor Mrs. S thought much of the incident. • A CT scan revealed the presence of a subdural hematoma, which was surgically evacuated. • Afterward, Mrs. S's confusion and disorientation cleared, and she returned to her normal state of functioning. 32.

[Audio] Management Plan 33. . . Management Plan. 33.

[Audio] Psychosocial Therapies 34. . . Psychosocial Therapies.

[Audio] The deterioration of mental faculties has significant psychological meaning for patients with dementia. The experience of a sense of continuity over time depends on memory. Patients lose recent memory before remote memory in most cases of dementia, and many patients are profoundly distressed by clearly recalling how they used to function while observing their noticeable deterioration. At the most fundamental level, the self is a product of brain functioning. Patients' identities begin to fade as the illness progresses, and they can recall less and less of their past. Patients' Emotional reactions ranging from depression to severe anxiety to catastrophic terror can stem from the realization that the sense of self is disappearing. 35.

[Audio] Structured Activities Clinicians can help patients find ways to deal with the defective functions, such as keeping calendars for orientation problems, making schedules to help structure activities, and taking notes for memory problems. Psychodynamic Assessment We should try to maximize any areas of intact functioning by helping patients identify activities in which successful functioning is possible. A psychodynamic assessment of defective functions and cognitive limitations can also be useful. Supportive and Educational Psychotherapy Patients often benefit from supportive and educational psychotherapy in which the clinician clearly explains the nature and course of their illness. They may also benefit from assistance in grieving and accepting the extent of their disability and from attention to self-esteem issues. 36.

[Audio] Clinicians can help caregivers understand the complex mixture of feelings associated with seeing a loved one decline and can provide understanding as well as permission to express these feelings. Psychodynamic interventions with family members of patients with dementia may be of great assistance. Those who take care of a patient struggle with feelings of guilt, grief, anger, and exhaustion as they watch a family member gradually deteriorate. Clinicians must also be aware of the caregivers' tendencies to blame themselves or others for patients' illnesses and must appreciate the role that patients with dementia play in the lives of family members. A common problem that develops among caregivers involves their self-sacrifice in caring for a patient. They often suppress any developing resentment from this self-sacrifice because of the guilt feelings it produces. 37.

[Audio] Neuro-Psychological Management • Neuro-psychological strategies are recommended by multiple medical organizations and expert groups. • Which include some of the manualised plans • Cognitive Training: Cognitive Retraining in Traumatic Brain Injury: Experience from Tertiary Care Center in Southern India ( Mohammed Afsar et al, 2021) Cognititve Stimulation : They are the preferred first-line treatment approach to it, except in emergency situations when it could lead to imminent danger or otherwise compromise safety. 38.

[Audio] S. no. Target functions Task Description 1 Processing speed; sustained attention Grain sorting The patients are given predefined quantity of a mix of two grains and the subject has to sort the grains separately by sorting one grain at a time in a limited time 2 Focused attention; response inhibition Shading The patients are given a simple geometrical shape printed on a white plain paper and the subject evenly shades it without crossing the boundaries in a limited time 3 Working memory Digit span A string of numbers is read to the patient and the patient must repeat it either forward or backward as instructed by the therapist; five items of forward and backward each were done in every session 4 Verbal learning and memory Temporal encoding A list of unrelated words was read out and the subject must repeat the first one-third of the list; same procedure was done for the last one-third and middle one-third of the list; free recall learning was done for five trials 5 Visual learning and memory Spatial encoding Three to six small daily use objects such as coin and key, eraser are placed on the table in predefined spatial arrangement and after an exposure of 10 seconds the patient must rearrange the jumbled objects in the same spatial arrangement 39.

[Audio] The Acceptability and Usefulness of Cognitive Stimulation Therapy for Older Adults with Dementia: A Narrative Review ( Hui Moon Toh et al , 2016) • The ADAS-Cog is one half of the Alzheimer's Disease Assessment Scale ( ADAS). • ADAS- Cog includes items such as word recall, naming, commands, constructional praxis, ideational praxis, orientation, word recognition, spoken language, comprehension, word-finding, and remembering instructions. • These items can be combined to form three subscales, namely, memory and new learning, language, and praxis. • Results showed that the items "commands" and "spoken language" showed significant difference favoring the intervention group and among the three subscales, intervention group improved significantly over the control group in language subscale. 40.

[Audio] • Some Application based Cognitive Trainings: CT Speech and Cognitive Therapy App : It includes over 100,000 therapy exercises that target a variety of speech and cognitive skills. Spaced Retrieval Therapy App : This method involves memorizing a fact, waiting one minute, quizzing yourself, then waiting five minutes, etc. Elevate : Some of the games are especially helpful for brain injury patients. For example, one game involves typing in the best synonyms for a word without using a list. This can help individuals who struggle with language difficulties like aphasia develop their vocabulary. Let's be Social app : is great for brain injury patients who want to improve their conversational skills and relearn appropriate behavior. 41.

[Audio] Neuropsychological Rehabilitation Program 42.

[Audio] A Neuropsychological Rehabilitation Program for Cognitive Impairment in Psychiatric and Neurological Conditions: A Review That Supports Its Efficacy ( Ainara Gomez-Gastiasoro et al, 2019) • REHACOP is a neuropsychological rehabilitation program based on a proven scientific methodology and with multiple evidence of efficacy in patients with different diagnoses. REHACOP •As a result of the study of this efficacy in different populations, there are already several national and international scientific publications in journals of high scientific impact. Scientific Publications •The development of Rehacop is the result of the work of several specialists in neuropsychology with more than 18 years of experience in the area. 18 years 43.

[Audio] It is a comprehensive and structured program, with eight work modules: Social skills Attention Language Memory Executive functions Daily life activities social cognition Psychoeducation 44.

[Audio] 300 Rehabilitation Exercises: • It consists of a total of 300 rehabilitation exercises, easy to administer with instructions and solutions, guidelines for the evaluation of change, follow-up sheets and suggestions on home exercises. Cognitive Subdomains: • The exercises are structured by cognitive subdomains and levels of difficulty. It includes recommendations and guidelines on how to evaluate the change or improvement, or how to collect and use the information in the work sessions with patients. Material: • The materials are • practical, • in color, • have instructions for patients and solutions for the therapist. 45.

[Audio] It can be used in individual or group sessions, and it is recommended that the therapist be someone with training in neuropsychology. 46.

[Audio] Conclusion • Cognitive functions are important for every aspect of human functioning. • Cognitive functions are the basis of adaptive behavior and holistic functionality in human beings. • Cognitive impairments have shown to negatively impact the activities of daily living in brain-injured patients. • Early interventions like cognitive training, cognitive stimulation and the various apps are very useful to improve and manage the cognition. • Though genetic factors also play an influence, the psychosocial factors support in delaying the damage that could happen due to various factors. 47.

. . References. • Pihlstrøm, L., Wiethoff, S., & Houlden, H. (2017). Genetics of neurodegenerative diseases: an overview. Handbook of clinical neurology, 145, 309–323..

[Audio] References • Jellinker KA. Basic mechanisms of neurodegeneration: acritical update. J Cell Mol Med. ( 2010) 14: 457- 487 • Burns, A., Guthrie, E., Marino-Francis, F., Busby, C., Morris, J., Russell, E., Margison, F., Lennon, S., & Byrne, J. ( 2005). Brief psychotherapy in Alzheimer's disease: randomised controlled trial. The British journal of psychiatry : the journal of mental science, 187, 143– 147. • Melo A, Monteiro L, Lima RMF, de Oliveira DM, de Cerqueira MD et al. Oxidative stress in neurodegenerative diseases: mechanism and therapeutic perspectives. Oxid Med Cell Longev. ( 2011) 2011: 467180 • Desai AK, Grossberg GT. Diagnosis and treatment of Alzheimer's disease. Neurology (2005) 64: S34–S39 • Sabbagh MN, Hendrix SB, Harrison JE. FDA position statement "Early Alzheimer's disease: developing drugs for treatment, guidance for industry." Alzheimer's Dement ( NY). 2019; 5: 13- 19. 49.

[Audio] References • Weintraub S, Wicklund AH, Salmon DP. The neuropsychological profile of Alzheimer disease. Cold Spring Harb Perspect Med. 2012; 2(4)a006171. • Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009; 62( 1): 42- 52. • FolsteinMF, FolsteinSE, McHugh PR. "Mini-mental state": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12( 3): 189- 198. • NasreddineZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005; 53(4): 695- 699. • Sabe L, Jason L, JuejatiM, Leiguarda R, Starkstein S. Sensitivity and specificity of the mini-mental state exam in the diagnosis of dementia. Behav Neurol. 1993; 6( 4): 207- 210. 50.