Dementia Diagnosis Lecture 7 PDF

LEC TURE 7 – DEMENTIA DIAGNOSIS Dr Melanie Burke SCHOOL OF PSYCHOLOGY UNIVERSITY OF LEEDS  LECTURE OUTLINE Date Lectur Details Theme e 1 Introduction to Ageing and Dementia 2 Biologic...

LEC TURE 7 – DEMENTIA DIAGNOSIS Dr Melanie Burke SCHOOL OF PSYCHOLOGY UNIVERSITY OF LEEDS  LECTURE OUTLINE Date Lectur Details Theme e 1 Introduction to Ageing and Dementia 2 Biological Ageing “HEALTHY 3 Cognitive Ageing AGEING AND THE BRAIN” 4 Neurophysiological and Psychosocial Ageing “Talking about Healthy Ageing” discussion 5 MCI – Diagnosis / Research “AGE-RELATED 6 MCI – Treatment DISEASES AND PATHOLOGY” 7 Dementia – Diagnosis / Research 8 Dementia – Treatment “Talking about Dementia” discussion 9 Living with Dementia “THE INTRA- 10 Dementia friendly INDIVIDUAL PERSEPCTIVE” 11 Revision – Feedback and Reflection  OVERVIEW OF TODAY’S LECTURE PART ONE What is Dementia? Alzheimer’s Disease – causes and diagnosis Vascular Dementia – causes and diagnosis PART TWO Frontotemporal Dementia – causes and diagnosis Lewy Body Dementia – causes and diagnosis Summary  PA RT O N E : D E M E N T I A DI A G N O S I S LIN IC A L S YM P T OM S ? WHAT ARE THE C  WHAT IS DEMENTIA? Dementia is not a disease per se, but a general term to describe the impaired ability to make decisions, remember and perform tasks of daily living (TDLs). TDLs refer to getting dressed, showering, cooking, 850, 000 people living with cleaning, navigation etc.. dementia in the uk (study from 2019) = 1 in 14 people It is not a part of “normal” 65+ years. ageing tends to only affect older Over 1.5 million people are adults. predicted to have Dementia in 2040 in the UK only. Dementia has a clear neurological basis whereby specific areas of the brain show accelerated neurodegeneration. https://www.gov.uk/government/publications/health-profile- for-england-2018/chapter-2-trends-in-mortality  Rates of disease mortality for MALES Rates of disease mortality for FEMALES  SHIFT IN LEADING CAUSE OF DEATH IN MAY 2023 Struggles ongoing and prevalence DEMENTIA CRISIS … The economic impact of dementia to our society each year is £26 billion, more than cancer and chronic heart disease combined, with over 80% of the cost carried by social and informal care. In 2017/18, government investment in dementia research was just £82.5M, equivalent to 0.3% of the total annual cost of Dementia. By contrast, government funding for cancer research stood at £269 million in 2015/16 – 1.6% of cancer’s £16.4 billion annual cost to the UK. There is a clear shortfall in funding to support Dementia and given people are living longer, this makes our society more susceptible to dementia which has yet to be realized. It’s worth noting that 1/10 Other’s report different prevalence individuals with Dementia of LBD and FTD, with LBD being have more than one type. more common ? DIFFERENT TYPES OF DEMENTIA https://www.nia.n ih.gov/health/al zheimers-disease- fact-sheet AL Z H E I M E R’ S DI S E AS E S E N I L E DE M E N T IA ) (AKA PR E  ALZHEIMER'S DISEASE (AD) - CAUSE Alzheimer’s disease is the most common form of Dementia and is characterized neuropathologically by the presence of neurofibrillary tangles (Tau protein) in the cell bodies and Amyloid plaque accumulation. This causes cell death (atrophy) and shrinkage in the brain. “ HOW DOES ALZHEIMER’S CHANGE THE BRAIN ? ” HTTPS://WWW.YOUTUBE.COM/WATCH?V=HEW1YQ_4 PAA Health (NIH) Research provides to following as some key symptoms in Alzheimer’s disease. Memory loss Poor judgment leading to bad decisions Loss of spontaneity and sense of initiative Taking longer to complete normal daily tasks Repeating questions Trouble handling money and paying bills Wandering and getting lost Losing things or misplacing them in odd places Mood and personality changes Increased anxiety and/or aggression FACTORS INVOLVE D IN AD PROGRES SION Singh et al. (2013). Acetylcholinesterase inhibitors as Alzheimer therapy: From nerve toxins to neuroprotection, European Journal of Medicinal Chemistry, Volume 70: 165-188 STAGES OF AD DIAGNOSIS https://www.jpreventionalzheimer.com/5015- diagnosis-of-early-alzheimers-disease-clinical- practice-in-2021-2.html https:// www.nia.nih.gov/ health/vascular- dementia V A S C U L AR D E ME N T I A  VASCULAR DEMENTIA(VD) - CAUSE Vascular dementia occurs due to reduced blood flow into and around the brain sometimes known as small vascular disease. It can present as a sudden change in cognitive abilities or show a slow deterioration over time and is caused by Cardiovascular Disease (CVD). This causes dysregulation of cerebral perfusion, blood–brain barrier (BBB) function, and neurovascular unit (NVU) coupling. Whereas AD is a linear decline. Vascular dementia can show a step- like change or progression in symptoms. https://youtu.be/GdkU5vCIpaU  Symptoms of Vascular Dementia Given the multiple types of vascular dementia, symptoms relate to where in the brain the damage is. For example temporal lobe damage will result in aphasia and memory loss, whereas damage in parietal areas are more likely to disrupt movements (apraxia). Post-stroke dementia is the result of a single large stroke. Small vessel dementia is the result of mini strokes or blockages in the brain.  N T Arnold Pick, a Czech O TEM P O R AL FRO neurologist and A psychiatrist, first DEME NTSEIASE) described the condition inK’S DI (AKA PIC 1892  FRONTOTEMPORAL DEMENTIA (FTD): CAUSES 3 main genetic mutations: 1) Abnormal Tau gene (MAPT gene) = accumulation of Tau protein causing neurofibrillary tangles in brain cells. 2) The GRN gene mutation leads to reduction in protein progranulin and make the TDP-43 protein go awry. 3) C90RF72 gene – an abnormal mutation of this gene (which is involved in RNA production and transport) can cause FTD and ALS (Amyotropic Lateral Sclerosis) aka FTD with MND. NB: These genetic variants tend to lead to behavioural variant frontotemporal dementia (see next slide).  TYPES OF FRONTOTEMPORAL DEMENTIA Behavioural variant frontotemporal dementia (bvFTD) ~8.7 FTD years Non Fluent Variant Primary ~9.4 years (aggramatic): nfPPA Progressive Aphasia (PPA) Semantic Variant: svPPA Movement Disorders (FTD- Linked with MND) ~3 Motor Neuron years Disease and Parkinson These sub-types are NOT discrete, ’s but overlap making diagnosis into different types challenging. Read Ljubenkov et al., 2016 for further info. FRONTOTEMPORAL DEMENTIA (FTD): GENERAL SYMPTOMS Socially inappropriate behavior – impulsivity, selfish/unsympathetic actions. Loss of mental flexibility, easily distracted, struggling to plan or organize. Decline in personal hygiene, overeating and loss of motivation. Language problems – slow speech, wrong word order, word repetition. Movement problems – slow, stiff and uncoordinated. Lack of bladder or bowel control. FRONTOTEMPORAL DEMENTIA (FTD): SUB-TYPE SYMPTOMS https:// www.psychiatrictime s.com/view/easy- miss-hard-treat- notes- frontotemporal- dementia “ Brian, an attorney, began having trouble organizing his cases. In time, his law firm assigned him to do paperwork only. Brian’s wife thought he was depressed because his father had died two years earlier. Brian, 56, was treated for depression, but his symptoms got worse. He became more disorganized and began making sexual comments to his wife’s female friends. Even more unsettling, he neither understood nor cared that his behaviour disturbed his family and friends. As time went on, Brian had trouble ” paying bills and was less affectionate toward his wife and young son. Three years after Brian’s symptoms began, his counselor recommended a neurological evaluation. Brian was diagnosed with behavioural variant FTD — the most common form of FTD. FTD IS THE MOST MISDIAGNOSED DEMENTIA A RECENT REVIEW SUGGESTS AROUND 72% OF PATIENTS ARE INITIALLY MISDIAGNOSED AS ANOTHER PSYCHIATRIC DISORDER  FTD: MISDIAGN OSIS ISSUE Frequency of reported symptom Worryingly this report identified that on average individuals get diagnosed with FTD 4.4 years after the onset of symptoms. Given life expectancy is from 10 years, this is a BIG issue in terms of accessing appropriate treatment and the right support (next Zapata-Restrepo lecture). L, Rivas J, Miranda C, Miller BL, Ibanez A, Allen IE and Possin K (2021) The Psychiatric Misdiagnosis of Behavioral Variant Frontotemporal Dementia in a Colombian Sample. Front. Neurol. 12:729381. doi: 10.3389/fneur.2021.729381 bvFTD: DIAGNOSIS Exclusion for Probably bvFTD bvFTD with bvFTD V. Exclusionary criteria for bvFTD All of the following symptoms (A–C) must be present to meet criteria. FTLD frontotemporal lobar Criteria A and B must be degeneration (FTLD) answered negatively for A. Meets criteria for possible bvFTD pathology any bvFTD diagnosis. B. Exhibits significant functional decline Criterion A and either Criterion C can be positive (by caregiver report or as evidenced by criterion B or C must be for possible bvFTD but Clinical Dementia Rating Scale or present to meet criteria. must be negative for Functional Activities Questionnaire A. Meets criteria for probable bvFTD. scores) possible or probable A. Pattern of deficits is C. Imaging results consistent with bvFTD bvFTD better accounted for by [one of the following (C.1–C.2) must be B. Histopathological other nondegenerative present]: evidence of FTLD on nervous system or C.1. Frontal and/or anterior temporal biopsy or at postmortem medical disorders atrophy on MRI or CT C. Presence of a known B. Behavioral disturbance C.2. Frontal and/or anterior temporal pathogenic mutation is better accounted for by hypoperfusion or hypometabolism on a psychiatric diagnosis PET or SPECT C. Biomarkers strongly indicative of Alzheimer’s disease or other neurodegenerative process svPPA: DIAGNOSIS Core features of Imaging svPPA Pathology for svPPA Both of the following core features must be present: Both of the following Clinical svPPA diagnosis (criterion A below) and either A. Impaired confrontation naming criteria must be present: criterion B or C must be B. Impaired single-word comprehension A. Clinical diagnosis of present: svPPA B. Imaging must show one A. Clinical diagnosis of At least three of the following other or more of the following semantic variant PPA diagnostic features must be present: results: A. Impaired object knowledge, B. Histopathologic evidence 1. Predominant anterior of a specific particularly for low-frequency or low- temporal lobe atrophy neurodegenerative familiarity items 2. Predominant anterior pathology (e.g. FTLD-tau, B. Surface dyslexia or dysgraphia temporal hypoperfusion or FTLD-TDP, AD, other) C. Spared repetition hypometabolism on SPECT C. Presence of a known D. Spared speech production (grammar or PET pathogenic mutation and motor speech) nfPPA: DIAGNOSIS Core features of Imaging svPPA Both of the following Pathology for nfPPA At least one of the following core criteria must be present: Clinical svPPA diagnosis (criterion features must be present: A below) and either A. Agrammatism in language production A. Clinical diagnosis of criterion B or C must be nonfluent/agrammatic present: B. Effortful, halting speech with variant PPA inconsistent speech sound errors and A. Clinical diagnosis of distortions (apraxia of speech) B. Imaging must show one nonfluent/agrammatic or more of the following variant PPA results: B. Histopathologic evidence At least two of the following other 1. Predominant left of a specific features must be present: posterior frontoinsular neurodegenerative A. Impaired comprehension of atrophy on MRI or pathology (e.g., FTLD-tau, syntactically complex sentences 2. Predominant left FTLD-TDP, AD, other) B. Spared single-word comprehension posterior frontoinsular C. Presence of a known C. Spared object knowledge hypoperfusion or pathogenic mutation hypometabolism on SPECT or PET  FTD-MND/FTLD: DIAGNOSIS With so many sub-types this FTD is very hard to diagnose. FTD-MND has clinical features of FTD, (often bvFTD), but also includes amyotrophic lateral sclerosis (ALS). Clinical features: synapse loss, gliosis, neuronal loss, and gross atrophy within the frontal and anterior temporal lobes. Presence of both Tau and TDP-43. Autosomal-dominant mutations (C9ORF72, MAPT, and GRN) that account for the most common known causes of familial FTLD. HERE ARE THE FULL FTLD CLASSIFICATIONS !  VEVOX TEST https://vevox.app/#/m/135749425 Session ID: 135-749-425  PAR T T W O : MORE T Y P E S O F DE M E N T I A  WIT H L EW Y BO D IES DEMENTIA (DLB) BO D Y DE ME NT IA) (AKA LEWY  DLB - CAUSES Second most prevalent of the Dementia’s after Alzheimer’s. Lewy bodies are alpha synuclein protein deposits, also present in Parkinson’s disease. Patients with Lewy Bodies also tend to have neurofibrillary tangles and Aβ plaques as found in other AD. Risk factors: Age of > 60 years Gender > in males Family history of Lewy Body Dementia or Parkinson’s.  DLB - GENETICS Dementia with Lewy Bodies is probably the most devastating of all Dementias. It has very rapid onset, can affect people as young as 40 years old and has the shortest mortality. Brand new research by Chia et al (2021) has found 5 genes that are linked to Lewy Bodies: GBA, TMEM175, BIN1, SNCA and APOE. They found that these genes are also linked to Parkinson’s and Alzheimer's Disease. This new research possible provides a pathways for effective screening. Chia, R., et al. (2021) Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture. Nature Genetics, February 15, 2021 DOI: 10.1038/s41588-021- 00785-3  DLB - SYMPTOMS The most common 5 symptoms of DLB: Hallucinations or Delusions of Reality – mainly visual. Cognitive Fluctuations – memory and attention problems. Changes in Movement – tremors, rigidity. Behavioral Shifts – change in mood/disposition/personality. Sleep Problems – insomnia and sleeping problems.  DLB - DIAGNOS IS DLB Depending on where the Lewy Bodies are located depends on whether the VERSUS individuals suffers from more PARKINSON Parkinsonian (i.e. motoric) or more Dementia (i.e. cognitive/behavioural) ’S DISEASE effects.  Atrophy is not such an obvious With AD clear atrophy in the anatomical feature of DLB as neurons hippocampus is classic of the don’t die they malfunction with the pathology Lewy body within the cell = harder to spot !! https://www.psychiatrictimes.com/view/easy-miss- hard-treat-notes-frontotemporal-dementia  CHALLENGES IN DEMENTIA DIAGNOSIS Delirium Depression Thyroid problems, liver, kidney, urinary tract infections and stroke also all have similar symptoms to MCI and Dementia. Visual and hearing impairments – vision loss can lead to bumping into things and lack of spatial awareness whereas hearing loss can cause social withdrawal and lack of Consider MCI and Dementia diagnosis as a engagement. series of tests that exclude other causes of the cognitive symptoms.  “Currently only about one-third of people with dementia receive a formal diagnosis at any time in their illness.” (National Audit NATIONA Office, 2007). L “...earlier diagnosis is a key DEMENTI component of the National A Dementia Strategy in the UK. However, early diagnosis is not STRATEG easy and no definitive test Y (2009) exists.” (Nicholl, 2009, BMJ Editorial)  DEMENT IA UK (2007, NATIONA L AUDIT OFFICE)  Less than two thirds of GPs “IMPROVI surveyed agreed they had access to specialist advice locally to help NG with diagnosing and managing dementia. SERVICES AND But a quarter disagreed that SUPPORT specialist services are best at FOR diagnosing dementia. PEOPLE WITH Three quarters of GPs said they were unaware of any protocol or DEMENTIA guidance for diagnosis and ” (NAO, management of dementia in their area 2007) SUMMARY OF TODAY’S LECTURE Cause/ Heredity Key pathologic Sympto ms / al Genetic features YOUR TURN: For you to complete ! READING LIST FOR TODAYS LECTURE: Ljubenkov PA, Miller BL. A Clinical Guide to Frontotemporal Dementias. Focus (Am Psychiatr Publ). 2016 Oct;14(4):448-464. doi: 10.1176/appi.focus.20160018. Epub 2016 Oct 7. PMID: 31975825; PMCID: PMC6519586. Tampi, Tampi, Parish (2020) Easy To Miss, Hard to Treat: Notes on Frontotemporal Dementia. Psychiatric Times: 37(10). https://www.psychiatrictimes.com/view/easy-miss-hard-treat-notes-frontotemporal-deme ntia Donaghy, P.C., McKeith, I.G. The clinical characteristics of dementia with Lewy bodies and a consideration of prodromal diagnosis. Alz Res Therapy 6, 46 (2014). Websites: https://www.nia.nih.gov/health/vascular-dementia https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet Further reading: Zapata-Restrepo L, Rivas J, Miranda C, Miller BL, Ibanez A, Allen IE and Possin K (2021) The Psychiatric Misdiagnosis of Behavioral Variant Frontotemporal Dementia in a Colombian Sample. Front. Neurol. 12:729381. doi: 10.3389/fneur.2021.729381.