Wk 13 - MC Questions PDF

HEENT 3 General anatomy of the mouth and sinuses Neurology of the olfactory and gustatory pathways BMS 200  Anatomy – Nose and Sinuses Upper nasal cavity boundary - cribriform plate of the ethmoid bone Lower boundary - hard palate Choanae 🡪 path to nasopharynx  Anatomy...

HEENT 3 General anatomy of the mouth and sinuses Neurology of the olfactory and gustatory pathways BMS 200  Anatomy – Nose and Sinuses Upper nasal cavity boundary - cribriform plate of the ethmoid bone Lower boundary - hard palate Choanae 🡪 path to nasopharynx  Anatomy – Nose and Sinuses Upper Boundary: Cribriform Plate of the Ethmoid Bone The cribriform plate is a horizontal, perforated bone structure that forms part of the ethmoid bone. It separates the nasal cavity from the cranial cavity and supports the olfactory bulb, which lies above it. The perforations in the cribriform plate allow the olfactory nerves (CN I) to pass through, facilitating the sense of smell. Any injury to this structure can result in cerebrospinal fluid (CSF) leakage into the nasal cavity (CSF rhinorrhea) and may disrupt the sense of smell.  Anatomy – Nose and Sinuses Lower Boundary: Hard Palate The hard palate forms the floor of the nasal cavity and is composed of: The palatine processes of the maxilla (anteriorly). The horizontal plates of the palatine bones (posteriorly). It separates the nasal cavity from the oral cavity below. The hard palate facilitates proper airflow during breathing and prevents food from entering the nasal cavity during swallowing  Anatomy – Nose and Sinuses Posterior Openings: Choanae The choanae (singular: choana) are funnel-shaped openings located at the posterior aspect of the nasal cavity. They connect the nasal cavity to the nasopharynx, which is the upper part of the pharynx behind the nasal cavity. The choanae serve as a passageway for airflow from the nasal cavity to the rest of the respiratory tract. Structures such as the vomer bone and medial pterygoid plates of the sphenoid bone contribute to the formation of the choanae.  Anatomy – Nose and Sinuses The nasal septum divides the nasal cavity into left and right passages and is composed of both bony and cartilaginous structures: Bony Components: Ethmoid Bone: Specifically, the perpendicular plate of the ethmoid forms the superior part of the nasal septum. It extends downward from the cribriform plate. Vomer Bone: The vomer forms the inferior and posterior part of the nasal septum. It is a flat, thin bone that articulates with the sphenoid, palatine bones, and maxilla. Cartilaginous Component: The septal cartilage forms the anterior portion of the septum, contributing flexibility and shape to the nose.  Anatomy – Nose and Sinuses Nasal Conchae The 3 nasal conchae (Superior, Middle, Inferior) are curved, bony projections on the lateral walls of the nasal cavity. They are covered in highly vascularized mucosa, which plays a role in conditioning inhaled air. Functions: Amplify Surface Area: The conchae increase the surface area of the nasal mucosa, optimizing the air-conditioning process. Induce Air Turbulence: As air passes over the conchae, it is swirled, promoting contact with the mucosa. Humidification: The mucosa warms and moistens incoming air to match body temperature and maintain respiratory tract function. Filtration: Particles and pathogens in inhaled air are trapped in the mucosal lining, protecting the lower respiratory tract. Olfactory Role: The superior concha helps direct air toward the olfactory region, enhancing the sense of smell.  Anatomy – Nose and Sinuses The meatuses are narrow air passages located between the nasal conchae and the lateral walls of the nasal cavity. Superior Meatus: Found below the superior concha. Function: Drains the posterior ethmoidal air cells. Facilitates airflow to the olfactory region for the detection of odors. Middle Meatus: Located below the middle concha. Contains the ethmoidal bulla, a bony prominence housing openings for the middle ethmoidal air cells. Includes the hiatus semilunaris, a curved groove through which the following structures drain: Frontal sinus. Maxillary sinus. Anterior ethmoidal air cells. Function: Critical for sinus drainage and ventilation. Inferior Meatus: Lies beneath the inferior concha. Contains the nasolacrimal duct, which drains tears from the lacrimal sac into the nasal cavity, explaining why the nose runs when we cry. Function: Helps maintain moisture in the nasal cavity.  Anatomy – Nose and Sinuses The nasal cavity's inner surface is lined with a specialized mucous membrane that varies depending on its region and function The mucous membrane within the nasal cavity is primarily composed of ciliated columnar epithelium, specializing in olfaction on the roof and upper surface of the superior concha.  Anatomy – Nose and Sinuses The Paranasal sinuses Are paired structures, named after the bones in which they are located. They communicate with the nasal cavity via small openings (ostia) Lined by mucous membrane, with a ciliated epithelial layer Ciliary action facilitates the transportation of sinus secretions into the nasal passages. Openings allow communication between the sinuses and nasal cavity These sinuses play a role in reducing the weight of the skull and serve as resonant chambers contributing to vocal resonance.  Anatomy – Nose and Sinuses Drainage pathways within the nasal cavity include: frontal sinus, which empties into the anterior part of the hiatus semilunaris through the infundibulum. The maxillary sinus and the anterior and middle ethmoidal sinuses also drain into the hiatus semilunaris. superior meatus receives drainage from the posterior ethmoidal sinuses. The sphenoid sinus drains into a recess above the superior concha. Anatomy – Nose and Sinuses Drainage: Tears from the conjunctival sac are carried into the nose through the inferior meatus, where the inferior end of the nasolacrimal duct opens.  Anatomy – Nose and Sinuses Sensory innervation: The sensory innervation of the nasal cavity is highly organized, with specific nerves responsible for transmitting olfactory and general sensory information Olfactory nerves (I) The olfactory nerves are specialized for the sense of smell (olfaction) Traverse the cribriform plate of the ethmoid bone to reach the olfactory bulb General sensation of the nasal cavity: ophthalmic (V1) and maxillary (V2) divisions of the trigeminal nerve contribute general sensory fibers to the nose. Anatomy – Nose and Sinuses Sensory innervation: The lateral nasal branches of the maxillary division of the trigeminal nerve convey sensation from the lateral wall of the nose. Sensation from the nasal septum is carried by the nasopalatine branch of the maxillary division of the trigeminal nerve.  Anatomy – Nose and Sinuses Arteries: sphenopalatine branch of the maxillary artery, which enters the nose from the pterygopalatine fossa. providing blood to the septum and lateral walls of the nasal cavity The vestibule of the nose (the front part of the nasal cavity) receives its blood supply from the superior labial branch of the facial artery. Anatomy – Nose and Sinuses Arteries: roof of the nose is supplied by the ophthalmic branch of the internal carotid artery – extensive anastomosis among all of these arterial branches  Anatomy – Oral Cavity The upper boundary of the mouth is formed by the palate, while the mylohyoid muscle defines its lower limit. The cheeks are framed by the buccinator muscles on either side, and the posterior boundary is marked by the palatoglossal arches. Beyond the oral cavity itself, the mouth encompasses the vestibule—an area situated between the teeth and the cheeks. Anatomy – Palate The hard palate results from the fusion of the palatal process of the maxilla and the horizontal process of the palatine bone Muscles of the soft palate: Tensor Veli Palatini, Levator Veli Palatini Palatoglossus Palatopharyngeus Musculus Uvulae. Anatomy – Palate Anatomy – Oral Cavity Tongue: Foliate, fungiform, filiform, and vallate papillae cover the surface of the front two-thirds of the tongue. Lingual tonsils, clusters of lymphoid tissue, are located in the posterior third of the tongue. Anatomy – Oral Cavity Muscles: The tongue is a highly flexible and muscular organ involved in various functions such as speaking, eating, and swallowing. Its movements are primarily controlled by intrinsic and extrinsic muscles Each contributing to the tongue's shape and mobility. Intrinsic muscles, arranged longitudinally, vertically, and transversely, constitute the bulk of the tongue's mass, contributing to alterations in its shape. Accompanying these intrinsic muscles, various extrinsic muscles facilitate tongue movement Genioglossus Muscle: functions to extend and lower the tongue. Hyoglossus Muscle: functions to lower and pull back the rear part of the tongue. Styloglossus Muscle: functions to lift and retract the tongue. Palatoglossus Muscle: acts on the tongue but is categorized as a muscle associated with the palate. Anatomy – Oral Cavity Anatomy – Oral Cavity Arteries supplying the tongue: lingual branch originating from the external carotid artery. Anatomy – Oral Cavity Floor of the Mouth Anatomy: Originating from the mandible's internal surface along a similarly named line, the mylohyoid muscle attaches to the anterior aspect of the hyoid bone. Functioning as a primary support for oral structures, the mylohyoid muscle actively participates in elevating the hyoid bone during swallowing and speech. Collaborating with the infrahyoid muscles, which stabilize the hyoid bone, the mylohyoid and digastric muscles work together to facilitate the depression of the mandible and the opening of the mouth.  Anatomy – Oral Cavity Innervation: Sensory Innervation: Touch, pressure, and temperature sensations from the tongue are conveyed by general sensory fibers. The lingual branch of the mandibular division of the trigeminal nerve (V3) carries general sensation from the anterior two-thirds of the tongue. The glossopharyngeal nerve (IX) is responsible for general sensation from the posterior third of the tongue. Taste sensation from the anterior two-thirds of the tongue is carried by the chorda tympani branch of the facial nerve (VII). Taste sensation from the posterior  Anatomy – Oral Cavity Innervation Motor Innervation: Branches of the vagus nerve (X) innervate all muscles of the palate, except the tensor veli palatini, which is innervated by the mandibular division of the trigeminal nerve (V3). The hypoglossal nerve (XII) innervates all muscles of the tongue, both extrinsic and intrinsic, with the exception of the palatoglossus muscle. The latter is considered a palate muscle and is therefore innervated by the vagus nerve (X). The nerve to the mylohyoid muscle, a branch of the mandibular division of the trigeminal nerve (V3), innervates the mylohyoid muscle and anterior belly of the digastric muscle. The facial nerve (VII) is responsible for innervating the posterior belly of the digastric and the stylohyoid muscle. Eye Physiology & Histology 1 General structure and function of the eye BMS 200 Outcomes Describe the anatomy of the eye, including the cornea, iris, lens, retina Describe the roles each major eye component plays in vision and the transmission of visual information, as well as how they interact Describe the structure and action of the retina, including the function of the photoreceptor cells (rods and cones) in converting light to electrical signals (signal transduction). The eye – getting familiar What does the eye do (basics)? Light-focusing functions: ▪ The shape of our lens changes to focus light precisely on the retina Depends on how far away the object is from the eye – refraction ▪ The size of the pupil changes to aid in focusing light precisely on the retina Makes the “pinhole” of our pinhole camera smaller – works together with refraction ▪ The movement of each eye relative to the other helps to give us stereoscopic (3-D) vision without blurring Extra-ocular muscles and their coordination What does the eye do (basics)? Transparency ▪ The cornea and the lens have a highly organized structure that keeps them as transparent as possible Transduction of light signals into two “action-potential 2-D maps” for each eye ▪ The photons are detected in our retina, and converted into electrical signals that are sent to the brain Protection - multiple structure in our eye protect it from physical, chemical and infectious damage ▪ Very tough sclera + fat in the orbit ▪ Lacrimal & mucosal secretions ▪ Eyelids and lashes (cilia) The eye – getting familiar Focusing: EOMs Ciliary body & ciliary muscles Iris The eye – getting familiar Transparenc y: Cornea Aqueous and vitreous humour Lens The eye – getting familiar Transductio n Retina The eye – getting familiar Protection Sclera Conjunctiva  Eye structures – anatomy and histology Composed of three layers (tunics) Sclera & cornea – fibrous tunic ▪ Supports eye shape, protection, site of attachment for EOMs ▪ Refraction Choroid, ciliary body, iris – vascular tunic Retina – neurosensory layer ▪ Nutrients, absorption of ▪ Signal transduction “stray” light, ▪ Initial processing of visual ▪ Pupillary constriction and information control of lens shape ▪ Absorption of “stray” light Fibrous layer basics Sclera – opaque, formed from dense irregular connective tissue ▪ Very strong structure, about 0.5 – 1 mm in thickness ▪ Extra-ocular muscles (EOMS) insert on the sclera in the anterior aspect ▪ Flat bundles of type I collagen, vasculature sits near the outer surface Cornea – transparent and completely avascular, composed of 5 layers ▪ External stratified squamous epithelium with a basement membrane (Bowman membrane) ▪ The thick stroma – very organized bundles of collagen ▪ An endothelium with a basement membrane (Descement membrane) The cornea Cornea histology facts Bowman’s membrane is strong and presents a barrier to infection The stroma is 99% of the thickness – uniform arrays of collagen fibres make it almost completely transparent ▪ Sparse keratocytes help to replenish the collagen The corneal endothelium helps to keep the cornea transparent and appropriately hydrated (transfers fluid from the anterior chamber) Limbus = area where the cornea merges with the sclera ▪ Where the bulbar conjunctiva also appears – more later ▪ Source of stem cells that migrate into the cornea Vascular tunic basics Also known as the uvea ▪ Three major parts include the choroid, the ciliary body, and the iris ▪ The lens is considered distinct from any of the 3 layers of the eye (the lens is weird) Choroid: ▪ Well-vascularized connective tissue with lots of melanocytes (absorb light instead of have it scattering throughout the eye) ▪ Only in the posterior 2/3 of the eye ▪ Composed of the choroidocapillary lamina… does exactly what it sounds like, lots of blood vessels ▪ Bruch’s membrane – layers of collagen and elastin that separate the retina from the choroid Vascular tunic basics Choroid (C) loose, vascular connective tissue with many melanocytes (lots in the suprachoroidal lamina, SCL) The choroid’s inner region, the choroidocapillary lamina (CCL), has a rich microvasculature Between the choroid and the retina is a thin layer of extracellular material known as Bruch’s membrane or layer (B) Vascular tunic basics Ciliary body – composed of the ciliary muscles, the ciliary processes, and the ciliary zonule Ciliary muscle – smooth muscle that connects to the zonular fibrils (composed of fibrillin) via the ciliary processes Ciliary processes – composed of a ridged, highly vascular region covered by epithelium ▪ Contains a great deal of melanin, helps keep light from entering the eye anywhere other than the pupil ▪ Epithelial cells also give rise to the zonular fibrils that form the suspensory ligament of the lens (ciliary zonule)  Simplified function – ciliary muscles and zonular ligaments FIGURE 10 – Accommodation solid lines = shape of the lens, iris, and ciliary body at rest dashed lines = shape during accommodation When gaze is directed at a near object, muscles contract 🡪 relaxation of the lens ligaments 🡪 lens becomes more convex  Production of aqueous humour Aqueous humour circulates from the posterior chamber to the anterior chamber of the anterior compartment ▪ Note – posterior compartment not involved here – don’t get it mixed up Highly vascular ciliary processes secrete aqueous humour from the posterior chamber ▪ Function – carries metabolites, maintains a cellular environment that optimizes proper refraction  Production of aqueous humour See 3-step process with image If drainage of aqueous humour is impaired, can result in massively increased intra-ocular pressures ▪ “pushes back” on the retina behind and can damage it ▪ Drainage for aqueous humour other than through the scleral venous sinus is very limited Production of aqueous humour The scleral venous sinus is found on the deep surface of the junction between the cornea and the sclera (aka limbus) The endothelium of the cornea is replaced by a complex filter, known as the trabecular meshwork, which lies over the scleral venous sinus ▪ Composed mostly of fibroblasts and ECM The iris can “flop over” the scleral venous sinus and block it The angle between the the iris and the Iris - basics Most anterior part of the uveal (vascular) layer and covers part of the lens ▪ Part it doesn’t cover = pupil ▪ Anterior surface is covered with fibroblasts and melanocytes and has no epithelial covering Deeper layer of the iris has myofibroblasts and the two major muscles that govern pupil size ▪ Dilator pupillae muscle – innervated by the sympathetic nervous system and extends along most of the iris ▪ Sphincter pupillae muscle – along the central surface of the iris, innervated by the parasympathetic nervous system  Iris - basics (a) The low-power micrograph shows a section of the central iris, near the pupil (P) (b) Stromal fibroblasts along the anterior surface (c) Dilator pupillae and sphincter pupillae Vitreous body - basics Transparent, gel-like connective tissue in the posterior cavity ▪ 99% water, collagen fibrils and hyaluronate also present ▪ Hyalocytes in the vitreous build the ECM of the vitreous ▪ Attaches to the surface of the retina at the inner limiting membrane Retina – the basics Embryologically derived from an “outpouching” of the diecephalon – histologically resembles the CNS ▪ Astrocytes, microglia, and a specialized type of glial cell known as a Muller cell ▪ Blood-retina barrier Nine layers – see next slide for descriptions ▪ Note – “inner” refers to the part closes to the vitreous, “outer” refers to the part closest to the choroid Can be divided functionally into: ▪ Rods and cones – transduce light information (NT release) ▪ Bipolar cells, ganglion cells, axons of ganglion cells – “line of communication” from rods and cones to the optic nerve ▪ Horizontal cells, amacrine cells – interneurons that modify the activity of many of these elements ▪ Pigment epithelium – supports rods and cones, lies on the Bruch’s membrane Layers of the retina  Differences across the retina Different areas of the eye contain different amounts of rods vs. cones ▪ Most cones are concentrated in the fovea ▪ The rest of the retina mostly There are no photoreceptors contains rods over the optic nerve – known as the physiologic blind spot The Lens Transparent, ectodermally-derived tissue with highly specialized epithelial cells known as lens fibres ▪ Elastic, but elasticity gradually decreases with age ▪ Viable cells found at the periphery, but at the center of the lens (mature lens fibres) the cells have lost their nuclei and are densely packed with a specialized proteins known as crystallins ▪ Lens fibres are derived from the simple cuboidal cells under the lens capsule known as the lens epithelium ▪ See image next slide The lens – structural basics LC = lens capsule, LE = lens epithelium DLF = differentiating lens fibres, MLF = mature lens fibres Abnormalities in the lens ▪ Loss of elasticity with age 🡪 presbyopia ▪ Opacities 🡪 cataracts  Accommodation and the lens (a) The lens flattens for distant vision when the ciliary muscles are relaxed, and the shape of the ciliary body holds the ciliary zonule taut (b) To see closer objects the ciliary muscle fibers contract, changing the shape of the ciliary body, relaxing tension on the ciliary zonule, and allowing the lens to The Eye – Part 1a Physiology Presented by: BMS200 Amna Noor Outline Eye Anatomy Optics Refraction Accommodation Visual Acuity Depth Perception Retina Overall structure and function Retinal Cells: Rods and Cones Structure and function Signal transduction Adaptation Visual Processing To finish next class Objectives Describe the anatomy of the eye, including the cornea, iris, lens, retina, optic nerve, oculomotor nerve, trochlear nerve, abducens nerve and other relevant structures, innervation and vascularization. Describe the roles each major eye component plays in vision and the transmission of visual information, as well as how they interact. Describe the basic concepts of light refraction and the manner in which they relate to how images are created on the retina. Describe the process of accommodation, including the role of and mechanism behind changing lens shape, pupil constriction, and eye convergence. Describe the structure and action of the retina, including the function of the photoreceptor cells (rods and cones) in converting light to electrical signals (signal transduction). Relate eye anatomy and physiology to the mechanism of depth perception Predict the shape of a corrective lens needed to correct myopia vs hyperopia Compare and contrast rods and cones with respect to night vision, visual acuity, and colour vision and differentiate the pathophysiology of protanopia and protanomaly. Describe the processes involved in light vs dark adaption. Outline Eye Anatomy Optics Refraction Accommodation Visual Acuity Depth Perception Retina Overall structure and function Retinal Cells: Rods and Cones Structure and function Signal transduction Adaptation Visual Processing Eye Anatomy: Reminder Eye Structure and Function - Review Light passes through cornea and enters the eye through the _______. The size of this structure is mediated by the _________. Light is bent as it passes through the various structures of the eye, but it is the ______ that can change its shape to focus the beams on the ________. Bending of light is called “refraction” - coming up: ▪ What are the principles of refraction, why does our eye need to refract light, and how does it do it? Optics Refraction Accommodation Visual Acuity Depth perception  Principles of Refraction Refraction = bending of light ▪ FYI: Occurs when light moves from a medium of one density to a medium of a different density, at a non-parallel angle What parts of the eye refract light? ▪ Although the cornea bends light the most, only the lens can change shape to control the amount of refraction https://commons.wikimedia.org/wiki/  Why do we need to refract light? No refraction: Beams go straight through, end up scattered Refraction: on retina. Beams are Would see bent to come multiple to a focussed images. point on the retina.image Note: See is one image. inverted on retina  Image of object in visual field is projected upside down and inverted on retina ▪ Brain needs to “flip” it back to right-side- up Visual Retina Fieldfields Top Bottom of Bottom Topretina of retina fields Right Left side of fields retina Left Right side of fields retina Lippincott Illustrated Reviews: Neuroscience, 2e  How does our eye refract light? Lens changes shape to refract/bend beams ▪ The more convex the lens, the more the beams are bent Convex = more rounded ▪ The closer the object, the more refraction needed: Why? Divergent beams from distant objects don’t make it into the eye, so don’t need to be refracted, whereas divergent beams from nearby objects do - Divergent beam from - Large refraction point source on required for distant object does divergent beam not enter eye, no from point source on refraction needed nearby object Optics Refraction Accommodation Visual Acuity Depth perception Accommodation Rounding of the lens is one step in “accommodation” ▪ Accommodation = the process the eye uses to focus on a nearby object Accommodation 1) Increasing convexity (rounding) of lens ▪ Under parasympathetic control ▪ Object moves closer Oculomotor nerve fires ▪ Ciliary muscle contracts Suspensory ligaments (aka ciliary zonule) relax and lens rounds up (more convex) Accommodat ion Distant vision: muscle Near vision: muscle relaxed, ligaments tight, contracted, ligaments  Another view of the interplay between the ciliary muscle, zonule fibers (suspensory ligaments) and lens during accommodation Accommodation 1) Review: Increasing ? of the lens 2) ? of the eyes ▪ Look at your classmate’s eyes as you move a pen progressively towards their nose What happens to the position of their eyes? ▪ What nerve and muscles are involved? Did you also happen to notice anything about their pupil… 3 = Changing the size of the pupil ▪ Would it dilate or constrict during accommodation? Why do you think this is? Accommodation 3) Constriction of pupil (miosis) Accommodation Bright light ▪ Parasympathetic control Oculomotor nerve stimulates pupillary sphincter of iris and pupil constricts (FYI: upto 1.5mm diameter) The pupil can also dilate (mydriasis) Fight/flight, dim light ▪ Sympathetic control Sympathetic nerves stimulate the radial pupillary muscles of iris and pupil dilates (FYI: upto 8mm diameter) https://commons.wikimedia.org/wiki/File:Iris-mus More on the lens… Normal Myopia or hyperopia = ▪ Defined by inability to focus beams from distant objects when lens is flat (ie ciliary Myopia (near-sighted) muscle relaxed) - eyeball too long: - Distant beams converge before retina - As object moves closer, beams start to converge on retina Hyperopia - As object moves even (far-sighted) closer, - eyeball too lens short: rounds up to continue to converge beams - If lens were flat,on retinabeams would distant converge “after” retina - How do you still see distant https://commons.wikimedia.org/wiki/ Optics Refraction Accommodation Visual Acuity Depth perception Visual Acuity How can you test for hyperopia or myopia? ▪ Eye chart: 20/20 vision is considered normal vision Furthest Furthest readable distance of chart for a ▪ What is better vision: 20/18 readable or 20/30? person with normal vision in feet distance of chart FYI:for TheaSnellen charts tests at 20 ft (6m), while the Rosenbaum card is a patient version in feet scaled down to 14 in (36cm) for convenience Vision Correction The strength of a corrective lens (ie how much it bends beams of light) is measured in diopters FYI: for a convex lens, a diopter is inversely related to the distance needed before parallel beams passing through the lens will converge. ▪ The higher the diopter, the more the beams are bent (ie the stronger the lens) Fun Facts (FYI only!): - The refractive power of our own eye lens can change from 20-34 diopters - The resting refractive power of eye is about 60 diopters (40 from cornea, 20 from lens) - Corrective lenses tend to range from 1 to 6 Vision correction Convex (+) vs concave (-) eyeglass lenses ▪ Which one causes beams to converge? Therefore, which one causes beams to diverge? ▪ What type of eyeglass lens can correct hyperopia? Therefore, what can correct myopia? Remember: The cornea is the eye structure that bends light to the greatest degree. Laser eye surgery involves re-shaping Vision correction FYI (actual shapes of Concav eye glass e lenses) Convex - What do you think a corrective lens prescription of OS - 5.0 means? - What about a prescription of OD +3.0? - Which of these Optics Refraction Accommodation Visual Acuity Depth perception  Depth perception Some contributors to depth perception: ▪ Moving parallax Imagine looking out the side window during a car ride: do closer or further objects leave your field of vision sooner? ▪ Access to previous knowledge If an object seems a lot smaller than what you know to be the normal size, is it close to you or far away? ▪ Stereopsis Based on binocular disparity: eyes are off-set, so each has a slightly different overlapping view. ▪ Results in retinal disparity: an image lands on different places in each retina Stereopsis is when the brain interprets the slightly different data picked up by each eye to form a perception of depth https://commons.wikimedia.org/wiki/  Stereopsis Fixed focus Stereopsis requires both eyes to fix on point: same point image projects to ▪ Fixed focus point projects to fovea fovea of both eyes (no disparity) ▪ Closer object projects to different places on each retina (retinal disparity) Example: Dog image falls on the left side of the fovea in the L eye, but on the right side of the fovea in the R eye. Note: In cases of large disparity you will see two images X X of the closer object when  Fixed focus Stereopsis point: image Stereopsis uses the retinal projects to disparity of two objects to contribute to depth perception fovea ▪ Example: For objects in front of a fixed focus point, the object that exhibits the greatest retinal disparity is the closest. X X X X Retina Overall structure and function Retinal Cells: Rods and Cones Structure and function Signal transduction Adaptation Visual Processing Back to the retina… Lippincott Illustrated Reviews: Neuroscience, 2e Claudia Krebs, Joanne Weinberg, Elizabeth Akesson, Esma Dilli (Fig 15.3) Layer Contents/Function Pigment layer Contains melanin to prevent diffuse scattering of light Contains vit. A to help rods and cones with photoreception Layer of rods and Contains the outer segments of rods (night vision), cones (colour vision) cones (Have photopigments to absorb light and begin the transduction of visual signals to the brain) Outer limiting Separates the outer segments of rods and cones from their cell bodies membrane Outer nuclear layer Contains the cell bodies of rods and cones (nucleus, organelles) Outer plexiform layer Transmission of visual signals from the synaptic terminal portion of rods and cones to other cell types (bipolar, horizontal cells) Inner nuclear layer Contains the cell bodies of other cells involved in the transmission and modulation of visual signals (bipolar, horizontal, and amacrine cells) Inner plexiform layer Transmission of visual signals among bipolar, amacrine, & ganglion cells Ganglionic layer Contains the cell bodies of ganglion cells Nerve fiber layer Contains optic nerve fibers (axons of ganglion cells) to carry visual signal signals to the brain Inner limiting Boundary between retina and vitreous humor membrane Blindspot test! Review: Considering the structure of the retina, why do we have a blindspot? Try it ☺ ▪ Roughly center yourself between the + and ▪ Cover left eye, look at “+” with right eye. Move closer to and further from the screen – what happens to the ? + Retina Overall structure and function Retinal Cells: Rods and Cones Structure and function Signal transduction Adaptation Visual Processing  Rods and Cones Basic structure: ▪ Outer segment Photopigments and Vit. A ▪ Inner segment Cell body ▪ Nucleus and organelles ▪ Synaptic terminal Releases glutamate to transduce visual signals Review: In which layer of the retina do you find each of these 3 parts of the rods and cones?  Rods and Cones: Comparison Chart Function Rods Cones Visual Poor Good Acuity - Highly convergent -Circuits not highly convergent circuits - Highly concentrated in fovea - Not found in fovea See next Night Vision Good Poor 2 slides -Contain high -Contain lower [photopigment] for [photopigment] - Require approx 100 photons example - Only need 1 photon of light for activation s of light to be activated Colour No Yes vision - No colour -Contain colour photopigments photopigments Convergence and Acuity Visual Stimulus Cones: Rods: Low High convergen converge ce nce Bipolar cells Brain registers good Brain registers poor  Acuity and Night Vision Have you ever noticed that a dim star you see in your peripheral vision disappears when you turn to look directly at it? Why is this? http://hyperphysics.phy-astr.gsu.edu/hbase/ Review: Visual Acuity Distribution: Review ▪ Cones highly concentrated in fovea (fovea has only cones) ▪ Rods concentrated more peripherally ▪ No rods or cones in blindspot – why? Colour Vision Cones are responsible for colour vision The three main types of cones are designated: S (detects short wavelengths) - blue M (detects medium wavelengths) - green L (detects long wavelengths) - red Other colours made by stimulating ratios of red, green and blue cones Ex: Yellow stimulates green and red close to optimally, but does not stimulate blue Lippincott Illustrated Reviews: Neuroscience, 2e Claudia Krebs, Joanne Weinberg, Elizabeth Akesson, Esma Dilli Colour Vision Why do the leaves on a tree appear green? What makes white? What about black? Colour Blindness Includes anopia and anomaly: Anopia = missing a type of cone Dichromy Anomaly = a defective type of cone (less sensitive) Trichromy Protanopia and protanomaly: red cone issue Red-green colour blindness Deuteranopia and deuteranomaly: green cone issue Red-green colour blindness Tritanopia and tritanomaly: blue cone issue Blue-yellow colour blindness Colour blindness Red-green colour blindness: X-linked recessive More likely in males or females? Normal Difficulty distinguishing green through red in spectrum Protanop ia Norma Protano Deuterano l pe pe http://www.colorvisiontesting.com/what-colorblind-people-see.htm Colour blindness Blue-yellow colour blindness Autosomal dominant, but rare Blues/greens hard to distinguish (can look grey), yellows/oranges hard to distinguish (can look pink) http://www.colorvisiontesting.com/wh at-colorblind-people-see.htm The Eye – Part 1b Physiology and Neurophysiology Dr. Heisel BMS200 Outline - Physiology Continued: Retina Overall structure and function (last day) Retinal Cells: Rods and Cones Structure and function continued (started last day) Signal transduction Adaptation Visual Processing  Rods and cones Rods and cones ▪ Contain photopigments ▪ Found in the saccules/disks of the outer segment Chromophore component = retinal (a derivative of which vitamin?) ▪ Pigmented ▪ Captures light and induces a conformational change in the opsin component Opsin component = G-protein coupled R ▪ Used for signal transduction Photopigments bring to mind photogenic  More on Photopigments Rod photopigment = Rhodopsin ▪ Remember, does not detect colour but is very sensitive to light Cone photopigment = Iodopsin ▪ Remember, not very sensitive to light but absorbs different wavelengths for colour detection ▪ L (long) = redder ▪ M (medium) = greener ▪ S (shorter) = bluerDiagram Reminder: Photopigments are comprised of retinal (“R”) and a G- Outline - Physiology Continued: Retina Overall structure and function Retinal Cells: Rods and Cones Structure and function Signal transduction Adaptation Visual Processing  Signal Transduction: Rods In response to light: ▪ Rhodopsin captures light, converting cis- to trans-retinal This activates the rhodopsin (now called meta-rhodopsin) ▪ Meta-rhodopsin activates the associated G-protein Involves G-protein = “Transducin” phosphodiesterase and ▪ G-protein signalling closes sodium channels cGMP Closure leads to ____ (hyper- or depolarization) of rod? ▪ Sodium channel closure decreases Glu release from rods Decreased Glu 🡪 depolarization & activation of “on-center” bipolar cells Turned on when light hits “on the center” of visual field Note - opposite process in the dark: - Cis-retinal 🡪 Na+ channels open 🡪 rod depolarization 🡪  Light in center of (Brighter visual field center, darker surround) G-protein (Meta- coupled rhodopsin) R βγ GD αβγ α GTP P Based on: Lippincott Illustrated Reviews: Neuroscience, 2e What happens to Claudia Krebs, Joanne release of On-center bipolar Weinberg, Elizabet glutamate: cells are Test Yourself at Home Rhodopsin (with cis retinal) Transducin: αβγ (G- (protein) GDP) Meta- βγ rhodopsin* (with __?__ retinal) Transducin*: α cGMP- (G- (GTP) protein) cGMP PDE cGMP- __?__ PDE* What happens Dementia BMS200 Dr. Nishanth Lakshman, Date: November 25th, PhD 2024 Learning Outcomes Review briefly the pathophysiology and risk factors of dementia, including Alzheimer’s Disease, Vascular Dementia, Lewy Body dementia, Frontotemporal Dementia, and Parkinson’s Dementia. Critique the evidence that hearing impairment is a modifiable risk for dementia. Develop a hypothesis for the pathophysiology of traumatic brain injury and its relation to the etiology of dementia. Critique the connection between gut microbiome and the pathophysiology of dementia  Dementia Dementia refers to a decline in cognitive ability acquired over time, leading to difficulties in successfully carrying out daily activities. The most frequently affected cognitive function in dementia is memory. This condition involves a significant cognitive impairment that hinders the ability to perform routine daily tasks. Disorders associated with dementia often exhibit distinctive cellular inclusions and the accumulation of extracellular proteins, accompanied by varying levels of glial and microglial activation.  Dementia Risk factors - Risks during early life (under 45 years), such as lower levels of education, impact cognitive reserve. Risk factors in midlife (45–65 years) and later life (over 65 years) contribute to the reserve and can initiate neuropathological processes. - Less education - Cognitive ability generally improves with education until it reaches a plateau in late adolescence, coinciding with the peak plasticity of the brain. Beyond the age of 20, there are relatively limited additional gains in cognitive ability with further education. - Cognitive decline - Individuals engaged in cognitively challenging occupations typically exhibit less cognitive decline both before and, in some cases, after retirement compared to those in less demanding jobs.  Dementia Risk factors - Hearing Loss - Hearing impairment in midlife, as assessed through audiometry, is linked to a more pronounced decline in volume in the temporal lobe, encompassing the hippocampus and entorhinal cortex. - Traumatic Brain Injury - In both humans and mouse models, a solitary and severe traumatic brain injury (TBI) is correlated with extensive hyperphosphorylated tau pathology. - Hypertension - Hypertension in midlife, defined as starting from the age of 40, was linked to diminished brain volumes and heightened white matter hyperintensity volume, while there was no observed association with amyloid deposition. - Alcohol - Consuming over 21 units per week and prolonged abstinence were both linked to a 17% rise in dementia risk compared to consuming less than  Dementia Risk factors - Obesity - Recent findings provide additional support for the connection between higher BMI and the development of dementia. - Smoking - Ceasing smoking, even in later years, lowers this risk. Exposure to second- hand smoke was linked to greater memory decline, and the risk escalated with the duration of exposure, even after accounting for other influencing factors. - Depression - It is also a component of the prodrome and initial phases of dementia. There is a potential for reverse causation, where depressive symptoms may arise from neuropathological changes associated with dementia that occur years before the clinical onset of dementia. - Social isolation - Social interaction, now acknowledged as a protective factor, boosts cognitive reserve or promotes positive  Dementia Risk factors - Physical Inactivity - Individuals may discontinue exercise due to the early signs of dementia, making inactivity both a potential consequence and a contributing factor in dementia. This relationship might be more pronounced as a risk factor in individuals with cardiovascular morbidity. - Air pollution - Studies on animal models indicate that airborne particulate pollutants expedite neurodegenerative processes by influencing cerebrovascular and cardiovascular diseases, Aβ deposition, and the processing of amyloid precursor protein. - Diabetes - In general, type 2 diabetes poses a distinct risk for the onset of subsequent dementia. - Lowering these risk factors could provide protection for individuals, regardless of whether they have a genetic predisposition or not. - Comprehensive interventions, such as addressing the intricate physical and social  Dementia - Pathophysiology Pathogenesis of Dementia The pathological anatomy of dementing diseases is frequently intricate and widespread, making it challenging to pinpoint and quantify specific areas. Memory impairment - central feature of many dementias - occurs with extensive disease in several different parts of the cerebrum, but the integrity of discrete parts of the diencephalon and of the medial temporal lobes is fundamental memory. Impairment of language function - associated specifically with disease of the dominant cerebral hemisphere, particularly the perisylvian parts of the frontal, temporal, and parietal lobes. Loss of capacity for reading and calculation - related to lesions in the posterior part of the left (dominant) cerebral hemisphere; Dementia - Pathophysiology Loss of use of tools and imitation of gestures (apraxias) - related to loss of tissue in the dominant parietal region. Impairment in drawing or constructing simple and complex figures with blocks, sticks, picture arrangements, etc. - observed with parietal lobe lesions, more often with right-sided (nondominant) than with left-sided ones. Problems with modulation of behavior and stability of personality - generally related to frontal lobe degeneration  Dementia - Pathophysiology Dementia of the degenerative types: - The clinical manifestation arising from cerebral disease is significantly influenced by both the location and the extent of the lesion. - Degenerative types of dementia are often associated with evident structural abnormalities in the cerebral cortex, but the diencephalon and basal ganglia are also implicated. - In some cases, dementia may stem from purely thalamic degenerations due to the integral relationship between the thalamus and the cerebral cortex, particularly concerning memory. - Alzheimer's disease serves as a notable example, here the primary site of damage is the hippocampus. However, the degeneration of the cholinergic nuclei in the basal frontal region, which project to the hippocampus, significantly exacerbates the decline in memory function. Dementia - Pathophysiology Dementia of the degenerative types - Biochemistry of the proteins: - Intracellular, especially intracytoplasmic, inclusions have a historical connection deeply intertwined with neurodegenerative disorders, being among the initial histologic abnormalities recognized in diseased cells. - The disruption of normal protein homeostasis likely plays a central role in the progression of these disorders. - In neurodegenerative disorders, the inclusions signify compromised native cellular proteins and their stress response conjugates. - Cells activate stress responses in the presence of damage; hence, the presence of stress response inclusions doesn't pinpoint the specific cause of damage but rather indicates the cellular attempt to protect itself. Dementia - Pathophysiology These accumulations of proteins can induce disease through various pathways.  Dementia - Pathophysiology Arteriosclerotic cerebrovascular disease - It follows a distinct trajectory compared to neurodegenerative diseases. - It results in multiple infarctions scattered throughout the thalami, basal ganglia, brainstem, and cerebrum, affecting motor, sensory, visual projection areas, as well as association areas. - Arteriosclerosis itself, in the absence of vascular occlusion and infarction, does not lead to progressive dementia. Instead, the cumulative impact of recurring strokes impairs intellectual function. - The progression of the disease, often evident in a step-by-step manner due to successive strokes, is typically observed in affected individuals, known as multi- infarct or vascular dementia.  Dementia - Pathophysiology Severe cerebral trauma lesions - They are typically located in the cerebral convolutions, particularly in the frontal and temporal poles, the corpus callosum, and the thalamus. - In certain instances, extensive degeneration of the deep cerebral hemispheres occurs due to mechanical disruption of the deep white matter, a phenomenon known as axonal shearing or diffuse axonal injury. - Some cases of dementia may involve mechanisms other than the outright destruction of brain tissue. - Chronic hydrocephalus, regardless of its origin, is frequently linked to a general decline in cognitive function. Although the compression of cerebral white matter is likely a contributing factor, this aspect has not been definitively established. - Similarly, extrinsic compression of one or both cerebral hemispheres by chronic subdural hematomas may yield a similar effect. Dementia - Pathophysiology *A diffuse inflammatory process is, at least in part, responsible for dementia in conditions such as syphilis, cryptococcosis, chronic meningitides, and viral infections like HIV encephalitis, herpes simplex encephalitis, and subacute sclerosing panencephalitis. Presumably, this involves both a loss of neurons and an inflammatory disruption of function in the remaining neurons. *Prion diseases, exemplified by Creutzfeldt-Jakob disease, lead to a widespread loss of cortical neurons, gliosis, and spongiform changes, resulting in distinct patterns of cognitive dysfunction. *Dementing states in adult forms of leukodystrophy typically manifest as a subcortical dementia syndrome with prominent frontal lobe features. Extensive white matter lesions may arise from advanced multiple sclerosis, progressive multifocal leukoencephalitis, or certain vascular dementias. Dementia - Pathophysiology The sequestration of proteins or other macromolecules renders them ineffective in their typical functions. As these aggregates grow, they can physically obstruct axons, dendrites, or the movement of materials within the cytoplasm. This process hampers cellular protein recycling and disrupts homeostasis. Initially, these aggregated proteins form ultrastructural fibrils that can be highly cytotoxic. Consequently, it seems that cellular stresses arising from various factors can disrupt proteostasis, leading to the formation of toxic fibrils that perpetuate and intensify cellular stress. Fundamentally, neurodegenerative diseases largely revolve around disorders of proteostasis, encompassing compromised cellular pathways controlling protein synthesis, folding, trafficking, aggregation, disaggregation, and degradation. Cerebral Cortical Neurodegenerative Diseases Alzheimer Disease (AD) - Alzheimer's disease (AD) constitutes the majority of neurodegenerative dementia cases, marked by the abnormal accumulation of two proteins: β-amyloid and tau. - AD is a gradual and progressive neurological disorder clinically characterized by memory loss, cognitive impairment, and eventual dementia. - It stands as the most prevalent form of dementia in the elderly, encompassing over half of all cases. - While Alzheimer's affects a maximum of 1%-2% of individuals under 65, the incidence rises to 40% or more in those aged 85 and above. - Women are affected twice as frequently as men. - Although most cases are sporadic, familial variants are also documented. Cerebral Cortical Neurodegenerative Diseases Alzheimer Disease (AD) – Pathology - In Alzheimer's disease (AD) brains, cortical atrophy is evident, accompanied by hydrocephalus ex vacuo. - The gyri narrow, sulci widen, and cortical atrophy is particularly noticeable in the parahippocampal regions. - Over the course of the disease, the atrophy of the temporal, frontal, and parietal cortex intensifies.  Cerebral Cortical Neurodegenerative Diseases Alzheimer Disease (AD) – Pathology: - Neuritic plaques (senile plaques) o Spherical deposits of β-amyloid accumulate extracellularly. o In the advanced stages of the disease, senile plaques occupy substantial volumes of the affected cerebral gray matter. o These plaques are encircled by reactive astrocytes and microglia, and they exhibit swollen, distorted neuronal processes known as dystrophic neurites. o While the detection of these plaques is essential for diagnosing Alzheimer's disease (AD), their quantity and distribution do not align closely with the severity of clinical disease. Cerebral Cortical Neurodegenerative Diseases Alzheimer Disease (AD) – Pathology: - Neurofibrillary Tangles o Collections of polymerized tau filaments are found intracytoplasmically. o The distribution of these filaments correlates with the clinical severity of Alzheimer's disease (AD). o Tangles in the entorhinal cortex and parahippocampal gyrus are observable in asymptomatic individuals many years before the typical onset age of AD, potentially signifying the earliest phases of the disease. Cerebral Cortical Neurodegenerative Diseases Alzheimer Disease (AD) - Pathology - Cytopathologic features include intracellular neurofibrillary tangles, composed partially of hyperphosphorylated forms of the tau protein that typically binds to microtubules, and extracellular amyloid plaques with a core of β-amyloid peptides, surrounded by altered nerve fibers and reactive glial cells. - The β-amyloid peptides are derived from amyloid precursor protein (APP), a transmembrane protein extending into the extracellular fluid from all nerve cells. - APP undergoes hydrolysis at three distinct sites by α-secretase, β- secretase, and γ-secretase: - α-secretase produces non-toxic peptides. - β-secretase and γ-secretase generate toxic peptides (40-42 AA). Cerebral Cortical Neurodegenerative Diseases Alzheimer Disease (AD) - Pathology - Toxic polypeptides aggregate extracellularly, adhering to AMPA receptors and Ca2+ ion channels, thereby augmenting Ca2+ influx. - These polypeptides also trigger an inflammatory response, resulting in the production of intracellular tangles. - Ultimately, the compromised cells undergo cell death, contributing to a third aspect of the brain pathology in individuals with this neurodegenerative disease: atrophy characterized  Cerebral Cortical Neurodegenerative Diseases Alzheimer Disease (AD) – Clinical Features: - Progressive decline in memory and cognitive abilities, along with challenges in language and alterations in behavior. - Individuals with mild cognitive impairment are now more readily identified, as they transition to full-blown dementia at a rate of approximately 15% per year. - Alzheimer's disease follows an unrelenting progression, transforming once intelligent and productive individuals into individuals who are demented, non-verbal, incontinent, and bedridden. - Common medical complications such as bronchopneumonia, urinary tract infections, and pressure ulcers often contribute to mortality.  Cerebral Cortical Neurodegenerative Diseases Alzheimer Disease (AD) – Clinical Features: AD occurs in three stages: - Presymptomatic - The patient does not exhibit cognitive impairment. There is a mounting body of evidence suggesting the accumulation of extracellular β-amyloid and the initiation of tangle formation, particularly in the hippocampus and adjacent temporal cortex. - Mild cognitive impairment (MCI) - Patients undergo a mild decline in memory and cognitive function that concerns them but doesn't disrupt their daily activities. A notable proportion of individuals with Mild Cognitive Impairment (MCI) will eventually develop Alzheimer's Disease (AD), although many will not. Those with low levels of CSF β-amyloid 1-42 or elevated amyloid load identified through positron emission tomography (PET) scanning seem more prone to advancing to AD. - Alzheimer Disease - Patients exhibit evident dementia upon clinical examination and neuropsychological evaluation. Impairments in activities of daily living are observed.  Cerebral Cortical Neurodegenerative Diseases Pick Disease (Frontotemporal Lobe Dementia - FTLD): - Distinguished by the accumulation of abnormal tau without β-amyloid. - Typically commences in the fifth to seventh decades, making it nearly as prevalent as Alzheimer's Disease in this age group. - In contrast to Alzheimer's Disease, which usually starts with memory difficulties, FTLD initiates with disruptive and inappropriate behavior. - Although the majority of frontotemporal dementia cases are sporadic, the disease has a strong hereditary component, with up to 40% of cases having a family history of dementia. Cerebral Cortical Neurodegenerative Diseases Pick Disease (Frontotemporal Lobe Dementia - FTLD): - It stands as the second most common cause of early-onset dementia in individuals under 65, constituting ten percent of pathologically confirmed cases. - Moreover, it is the third most common cause of dementia in individuals over 65. - Commonly known as Pick's disease, this dementia syndrome frequently occurs in pre-senile patients and is categorized into behavioral variant (bvFTD) and primary progressive aphasia (PPA) subtypes. Cerebral Cortical Neurodegenerative Diseases Pick Disease (Frontotemporal lobe dementia - FTLD) - Pathology - In Pick disease, cortical atrophy primarily occurs in the frontotemporal regions. - The atrophy can reach severe levels, causing affected gyri to be reduced to thin slivers, a condition known as knife-edge atrophy. Cerebral Cortical Neurodegenerative Diseases Pick Disease (Frontotemporal lobe dementia - FTLD) - Pathology - The affected cortex experiences a significant loss of neurons and displays pronounced astrogliosis. - Residual neurons exhibit highly argentophilic and tau-immunoreactive round cytoplasmic inclusions known as Pick bodies. These formations result from densely aggregated straight tau filaments A. In hematoxylin and eosin– stained sections, Pick bodies are basophilic, spherical, intracytoplasmic, intraneuronal aggregates of tau protein (arrows). They tend to be round rather than angular like the neurofibrillary tangles (NFTs) in  Cerebral Cortical Neurodegenerative Diseases Pick Disease (Frontotemporal lobe dementia - FTLD) – Clinical Features - Three main clinical syndromes: 1. Behavioral variant Individuals afflicted with this disorder demonstrate a gradual and progressive onset of personality and associated abnormalities. These may encompass apathy, disinhibition, perseveration, impaired judgment, limited abstraction ability, loss of empathy, bizarre affect, eating disorders, and a general sense of disengagement. Insight is typically compromised, and some individuals may exhibit euphoria or repetitive compulsive behaviors. Notably, an initial diagnosis of depression is often encountered.  Cerebral Cortical Neurodegenerative Diseases Pick Disease (Frontotemporal lobe dementia - FTLD) – Clinical Features - Three main clinical syndromes: 2. Primary Progressive Aphasia Semantic variant In the semantic variant, individuals gradually experience a decline in their capacity to comprehend the meaning of words, objects, individuals, and specific emotions. 3. Primary Progressive Aphasia Nonfluent/agrammatic variant Experience a profound difficulty in generating words, frequently accompanied by noticeable motor speech impairment. - Motor neuron disease may accompany any of these three clinical syndromes. - Frontotemporal dementia (FTD) can occur sporadically or be inherited. Symptomatic sporadic Pick disease typically manifests in mid-adult life and advances relentlessly, leading to death in 3–10 years. Cerebral Cortical Neurodegenerative Diseases Lewy Body Disease (LBD): - Presenting as either Parkinson’s disease and dementia (PDD) or dementia with Lewy bodies (DLB), Lewy body disease (LBD) ranks as the second most prevalent cause of neurodegenerative dementia, following Alzheimer’s disease (AD). - The disease is characterized by the widespread engagement of cortical neurons with Lewy body inclusions and is distinguished by the absence or a limited number of neurofibrillary tangles and amyloid plaques. Cerebral Cortical Neurodegenerative Diseases Lewy Body Dementia (LBD) – Pathophysiology: - The development of Lewy body dementia (LBD) is believed to involve both genetic and environmental factors. - The identification of alpha-synuclein aggregates in Lewy bodies has led to the recognition of α- synuclein duplications and triplications, which clinically manifest as Parkinson's disease (PD) or dementia with Lewy bodies (DLB). Cerebral Cortical Neurodegenerative Diseases Lewy Body Dementia (LBD) – Pathophysiology: - Lewy bodies, characterized as intraneuronal cytoplasmic inclusions, consist of straight neurofilaments measuring 7–20 nm in length, surrounded by amorphous material. - These bodies contain epitopes recognized by antibodies against phosphorylated and nonphosphorylated neurofilament proteins, ubiquitin, and α-synuclein. Cerebral Cortical Neurodegenerative Diseases Lewis Body Disease (LBD) – Pathophysiology - The principal neuropathological hallmark in LBD is the distribution of Lewy bodies and Lewy neurites across specific brainstem nuclei, the substantia nigra, amygdala, cingulate gyrus, and ultimately, the neocortex. - The presence of α-synuclein aggregates in neurons and glia molecularly categorizes Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) as synucleinopathies. Cerebral Cortical Neurodegenerative Diseases Lewy Body Disease (LBD) – Pathophysiology - Formal criteria delineate three progressive stages: (1) Brainstem predominant; (2) transitional limbic; and (3) diffuse neocortical. - PD typically begins with nonmotor features such as constipation and/or hyposmia, followed by anxiety, depression, rapid eye movement sleep behavior disorder (RBD), parkinsonism, and ultimately dementia. The clinical manifestation of PDD occurs when limbic and cortical areas are affected. - A significant cholinergic deficit, stemming from involvement of the basal forebrain and pedunculopontine nucleus, is prevalent in most DLB patients and may be linked to characteristic fluctuations, inattention, and visual hallucinations Cerebral Cortical Neurodegenerative Diseases Lewis Body Dementia (LBD) – Clinical Features - Most researchers view PDD and DLB as different points along a spectrum of LBD pathology. In terms of cognition, both PDD and DLB typically present with marked executive, attentional, and visuospatial deficits, while episodic memory tends to remain relatively preserved. - Cognitive decline in LBD extends to impact daily living activities beyond other symptoms associated with Parkinson's disease. Cerebral Cortical Neurodegenerative Diseases Lewis Body Dementia (LBD) – Clinical Features - In DLB, early psychosis, featuring well-formed visual hallucinations, fluctuating cognition, rapid eye movement sleep behavior disorder (RBD), and parkinsonism, serves as the primary diagnostic criteria. - RBD, often prodromal, is a distinctive feature where patients act out their dreams, sometimes violently, potentially causing harm to themselves or their bed partners. Cerebral Cortical Neurodegenerative Diseases Lewis Body Dementia (LBD) – Clinical Features - Anosmia is also more indicative of LBD. - Both PDD and DLB have a prodromal phase characterized by mild cognitive impairment (MCI), where cognitive deficits do not significantly affect daily life. - Prodromal DLB shares similar cognitive disturbances with PDD but is also associated with hallucinations unrelated to medications, RBD, fluctuations in attention, or parkinsonism.  Vascular Dementia Traditionally, the phrase "vascular dementia" has been employed to characterize a subset of dementia cases primarily attributed to one or more symptomatic strokes. This condition is notably prevalent in populations with limited access to medical care, where vascular risk factors tend to be inadequately treated. The term "vascular contributions to cognitive impairment and dementia" (VCID) has emerged to acknowledge the observation that pathological changes involving the cerebral vasculature are highly prevalent in the elderly and contribute to cognitive impairment, either in isolation or, more commonly, in conjunction with other neurodegenerative processes. Both symptomatic strokes and asymptomatic vascular lesions, often identified through brain magnetic resonance imaging (MRI) scans, play significant roles in contributing to cognitive impairment. Approximately half of stroke survivors exhibit some degree of cognitive impairment, and this impairment tends to increase progressively with extended follow-up periods. Vascular Dementia Subtypes of Cerebrovascular Disease Associated with VICD: Large Cerebral Strokes - Symptomatic strokes, whether ischemic or hemorrhagic, signify irreversible damage to specific regions of the cerebral cortex, subcortical white matter, or other subcortical and infratentorial structures. The resulting cognitive impairment is influenced by the size and location of these strokes. - The occurrence of multiple strokes and larger volumes of infarcted territory is correlated with an increased probability of poststroke cognitive dysfunction.  Vascular Dementia Cerebral Small-Vessel Disease - Frequently lacks clinical symptoms and is typically identified only during assessments for cognitive decline or other related symptoms. - The two prevalent age-related pathologies associated with cerebral small vessels are arteriolosclerosis and cerebral amyloid angiopathy. - Arteriolosclerosis involves the thickening of arterioles due to the infiltration of plasma proteins into the vessel wall. - Cerebral amyloid angiopathy is characterized by the deposition of the β-amyloid peptide in the walls of small cerebral arteries, arterioles, and capillaries, leading to the loss of normal wall structure. - Despite differences in their underlying pathogenic mechanisms, both cerebral small- vessel diseases result in a similar spectrum of ischemic and hemorrhagic brain lesions.  Vascular Dementia Influence of Concurrent Brain Pathologies - Several studies examining clinicopathologic correlations have confirmed that when cerebrovascular and neurodegenerative lesions coincide, the resulting cognitive and functional decline exceeds what would be anticipated based on the impact of each disease mechanism when considered separately. - The synergy between cerebrovascular and neurodegenerative processes could also play a role in the development of dementia. - These interactions may encompass the compromise of the blood-brain barrier, potentially allowing the infiltration of neurotoxic or inflammatory agents into the brain. - Additionally, there may be disruptions in the clearance of β-amyloid and other pathogenic molecules from the brain, postulated to occur through perivascular drainage pathways influenced by physiological vascular motion. Hearing Impairment and Dementia Sensorineural hearing loss (SNHL) in the elderly is typically characterized as age-related SNHL. Various mechanisms contribute to the decline in auditory function, and the manifestations can vary depending on the affected segment of the auditory pathways. Brain atrophy serves as a common factor connecting cognitive decline, Mild Cognitive Impairment (MCI), Alzheimer’s Disease (AD), and hearing loss. Indeed, all these conditions contribute to brain atrophy. In a cross-sectional study encompassing 6,451 individuals intended to be representative of the US population, with an average age of 59.4 years, a decline in cognition was observed with each 10 dB reduction in hearing. This decline persisted even below the clinical threshold, indicating that subclinical levels of hearing impairment (below 25 dB) were significantly associated with lower cognition.  Hearing Impairment and Dementia Several theories have been proposed: - Increased Cognitive Load: Hearing loss likely elevates the cognitive effort needed to process and comprehend speech, as diminished or distorted sensory input demands increased cognitive engagement. This could lead to relevant structural changes in the brain and neurodegeneration, impacting other cognitive processes such as working memory. - Changes in Brain Structure and Function: Hearing loss is associated with a decrease in the overall volume of the brain and the primary auditory cerebral cortex in the temporal lobe. Chronic hearing impairment also results in reduced activation of central auditory pathways, dysfunction of the auditory– limbic pathway, and atrophy of the frontal lobe and hippocampus. Hearing Impairment and Dementia - Common Pathological Conditions: Both hearing loss and cognitive impairment stem from a shared neurodegenerative process in the aging brain, involving the degeneration of the stria vascularis, loss of hair cells and primary afferent neurons, and alterations in neurotransmitter release. - Social Disengagement: Challenges in communication arising from hearing loss can lead to social isolation, considered a risk factor for cognitive disorders. This isolation may result in reduced cognitive stimulation, apathy, and potentially depression. Social withdrawal also triggers negative biological mechanisms, including increased transcription of pro- inflammatory genes, thereby elevating the overall inflammatory status—a significant risk factor for potential damage to cerebral functions. Hearing Impairment and Dementia Traumatic Brain Injury (TBI) and Dementia Beyond the immediate debilitating effects, severe traumatic brain injury (TBI), particularly recurrent mild TBIs, can trigger prolonged neurodegenerative processes that result in pathological features resembling those seen in Alzheimer's disease (AD). While post-traumatic neurodegeneration is a frequent occurrence, determining specific types of post-traumatic dementia in clinical practice remains uncertain. There is evidence suggesting that cerebrovascular dysfunction (CVD) plays a crucial role in the onset of dementia following TBI. Traumatic Brain Injury (TBI) and Dementia 1. Considering the research article (Ramos-Cejudo, et al.) provided in this lecture, what are your reflections on the cerebrovascular connection between traumatic brain injury (TBI) and dementia? 2. Can you formulate a hypothesis regarding the pathophysiology of traumatic brain injury and its connection to the etiology of dementia? Gut Microbiome and Dementia Accumulating evidence indicates a significant role of the intestinal microbiota in the initiation and progression of neurodegenerative diseases. Recent reports have highlighted a connection between dysfunctions in the intestinal microbiota and dementia. The mounting data suggest that the gut microbiota actively contributes to the development of various conditions, including obesity, diabetes, cancers, aging, autoimmune diseases, and neuropsychiatric disorders like depression and Alzheimer's disease (AD). The involvement of gut microbiota in AD pathogenesis is realized through diverse pathways, including abnormalities in Aβ, tau phosphorylation, neuroinflammation, neurotransmitter dysregulation, and oxidative stress. Nevertheless, the precise roles and mechanisms of gut microbiota in individuals with AD remain unclear. Gut Microbiome and Dementia Drawing on the earlier discussion and the attached course article, review the case below and attempt to answer the following questions for yourself: - Can you evaluate the suggested mechanism for how dysbiosis influences the onset of dementia by identifying limitations in their hypothesis? - In addition to the mechanisms proposed in current research, what other hypotheses related to microbiota do you believe play a role in the onset of dementia? Case: Mrs. Anderson, a 65-year-old retired teacher, has been experiencing memory loss, difficulty with language, and changes in behavior over the past two years. Her family has noticed these progressive cognitive decline symptoms and has sought medical advice. Mrs. Anderson does not have a significant medical history, but her family reports that she has struggled with gastrointestinal issues, including irregular bowel movements and occasional abdominal discomfort. Post-Assessment - MCQ Which of the following neurodegenerative diseases is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain? A) Vascular dementia B) Lewy body dementia C) Frontotemporal dementia D) Alzheimer's disease Post-Assessment - MCQ Which of the following neurodegenerative diseases is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain? A) Vascular dementia B) Lewy body dementia C) Frontotemporal dementia D) Alzheimer's disease Post-Assessment - MCQ Which type of dementia is associated with motor symptoms such as tremors, rigidity, and bradykinesia? A) Alzheimer's disease B) Vascular dementia C) Lewy body dementia D) Parkinson's dementia Post-Assessment - MCQ Which type of dementia is associated with motor symptoms such as tremors, rigidity, and bradykinesia? A) Alzheimer's disease B) Vascular dementia C) Lewy body dementia D) Parkinson's dementia Post-Assessment - MCQ Which type of dementia is associated with a gradual decline in cognitive function due to multiple small strokes or impaired blood flow to the brain? A) Alzheimer's disease B) Vascular dementia C) Lewy body dementia D) Frontotemporal dementia E) Parkinson's dementia Post-Assessment - MCQ Which type of dementia is associated with a gradual decline in cognitive function due to multiple small strokes or impaired blood flow to the brain? A) Alzheimer's disease B) Vascular dementia C) Lewy body dementia D) Frontotemporal dementia E) Parkinson's dementia