Aging Week 3 Summary 3 PDF

3.1 aging changes in the neurological system degeneration of the CNS neurodegenerative conditions and aging ex: - PD -ALS - HD - risk factor: increasing age primary hallmarks of aging driving neurodegeneration - genomic instability: - DNA damage over time - incr...

3.1 aging changes in the neurological system degeneration of the CNS neurodegenerative conditions and aging ex: - PD -ALS - HD - risk factor: increasing age primary hallmarks of aging driving neurodegeneration - genomic instability: - DNA damage over time - increased need for DNA repair - decreased levels of NAD+ and sirtuins telomere attrition - shortening of telomeres w age - impact on cellular aging epigenetic alterations - changes in gene expression regulation loss of proteostasis - decline in protein quality control - accumulation of misfolded proteins mechanisms and effects DNA damage and repair - ongoing DNA damage leads to cellular synthesis - increased overall inflammation mitochondrial dysfxn - contributes to decreased central nervous system function inflammation - accelerates the aging process - interaction of genomic instability, telomere attrition, epigenetic changes, and proteostasis loss leads to neurodegeneration - aging as a significant risk factor for neurological diseases thru these mechanisms changes in brain structure ventral dilation and neuron changes ventral Dilation - some degree is expected w aging cortical neurons - shrinkage occurs - # remains relatively the same cortical atrophy affected areas: - frontal cortex - temporal cortex - prefrontal cortex - potentially the hippocampus (memory capacity) minimal atrophy: - subcortical nuclei, except possibly the substantia nigra - impact on dopamine use by the strata brain wt and size - atrophy effect: - decrease in brain wt w age variability: - normal variability in brain sizes among individuals  normal aging involves specific patterns of atrophy and neuron shrinkage significant areas include the frontal and temporal cortices, and potentially the hippocampus, w minimal impact on subcortical nuclei except the substantia nigra physiologic changes to vasculature in the CNS arterial wall changes loss of elasticity: - increased likelihood of atherosclerosis (not considered normal aging) tortuosity: - vessels become more tortuous or windy - slower perfusion of brain tissue BBB Changes - decreased protectiveness: - decreased waste elimination - impaired reactivity in brain vasculature to meet demands neural processing efficiency reduced efficiency: - decreased myelin - decreased vasodilation capacity changes in the brain's vascular system contribute to reduced neural processing efficiency includes loss of arterial elasticity, increased vessel tortuosity, decreased blood-brain barrier protectiveness, and impaired waste elimination and vasculature reactivity impact on cognition seattle longitudinal study findings overall cognition: - linear age-related declines observed areas of rapid decline: - processing speed - episodic memory - spatial ability - reasoning minimal change: - numeric ability - verbal ability cognitive decline and mortality related studies: - plotted mortality based on cognitive decline acceleration of cognitive decline: - begins approximately 3-6 years before death significant cognitive declines in certain areas w aging acceleration of cognitive decline near end of life impact of cognition fxn memory and processing speed short term memory: - modest decline processing speed: - continued decline throughout adulthood verbal intelligence and personality verbal intelligence: - stable until the 60s personality: - no substantial changes sleep patterns variability: - more variable sleep patterns and duration frequent awakenings and naps: - increased frequency challenges w normal aging info processing: - decreased fluidity and speed impacting intelligence attention: - decreased stability to divide attention executive tasks: - challenges w new tasks learning and recall: - decreased learning and recall of new info word finding: - challenges w spontaneous word finding mental flexibility and reaction time: - decreased mental flexibility - increased reaction time maintained fxns independence w general fxns: - attention span - real world executive fxn - comprehension and vocabulary - long-term procedural memory aging involves specific cognitive and functional changes while maintaining certain abilities and independence in general fxns reversible changes focus: evidence supporting reversibility of cognitive decline with physical activity and nutrition accelerated changes and cognitive impairment - early onset: - accelerated changes leading to mild cognitive impairment (MCI) or dementia impact of physical activity - mitigation and reversal: - role of physical activity in reducing and possibly reversing biological hallmarks of aging role of nutrition - mitigating effects: - contribution of nutrition to combating aging-related cognitive decline future directions - research trends - further investigation into mechanisms of reversibility - integration of physical activity and nutrition in cognitive health strategies both physical activity and nutrition demonstrate potential to mitigate and reverse buildup of aging biological hallmarks associated with cognitive decline continued research is crucial to fully understand and optimize these interventions in the peripheral nervous system brain fxn processing and reaction time: - decreased w age - impact on overall cognitive fxn peripheral nervous system - impact on sgnaling feedback: - quality and quantity affected by decreased fxn structural changes in the PNS myelin sheath health: - decreased due to impaired remyelination by oligodendrocytes nerve conduction velocity: - slowed due to reduced myelin integrity other impacts on PNS endoneurial blood flow: - decreased nerve regeneration and repair capacity: - impaired - protein transport: - affected microglia and astrocytes fxn: - impaired fxn neuromuscular jxn changes structural alterations: - impact on nerve signaling aging affects both central and PNS fxn decreased processing and reaction time influences somatosensory, visual, and vestibular signaling structural changes in the PNS contribute to reduced nerve conduction velocity, impaired regeneration, and altered neuromuscular junction signaling impact on PNS fxn vision depth perception and visual acuity: - difficulty due to decreased lens elasticity - impacts on accurate depth perception hearing - upward gaze and high-frequency sounds: - limitation of upward gaze - loss of acuity for high-frequency sounds somatosensory and spinal reflexes general changes: - altered processing in somatosensory perception - changes in spinal reflex responses gait and posture age-related changes: - normal alterations in gait and posture - not typically leading to false perceptions or balance issues aging affects sensorineural processes across vision, hearing, somatosensory perception, spinal reflexes, gait, and posture important to note changes in depth perception, visual acuity, upward gaze, high-frequency sound perception, and normal gait and posture alterations impact on vision cataracts - blurry vision due to protein buildup on the lens - no change in field of vision impact: - overall vision becomes progressively blurry glaucoma - optic nerve damage caused by elevated intraocular pressure - leads to tunnel vision impact: - gradual loss of peripheral vision macular degeneration - degeneration of the macula, central part of the retina - decreased central vision impact - increased reliance on peripheral vision -cataracts: blurry vision without peripheral vision loss -glaucoma: tunnel vision due to peripheral field loss -macular degeneration: central vision loss, increased dependence on peripheral vision these conditions represent abnormal changes in vision with age, necessitating medical attention Summary Known changes in nervous system function and structure occur with age, but are reversible this bish..stays doing the most. this shouldnt be 5 pages  3.2 impact of exercise on aging neurological system physiological impact in the CNS intro to exercise and metabolic switching - exercise induces intermittent metabolic switching - body's response to demands leads to metabolic rate changes effects on ketones and synaptic activity - increased buildup of ketones - enhanced synaptic activity impact on trophic factors - brain derived neurotrophic factor (BDNF) - fibroblast growth factor 2 (FGF-2) - vascular endothelial growth factor (VEGF) activation of signaling pathways - concurrent activation of pathways - Induction of transcription factors enhancement of neuroplasticity and resilience - genes encoding proteins for neuroplasticity - resilience during aging overall effect on physiological aging - minimization of maladaptations - promotion of healthy aging processes impact on cerebral blood flow impact of exercise on brain - increased cerebral blood flow and basal reactivity - decreased brain atrophy over time cognitive fxn improvement - neuroprotection effects - increased cerebral vascular and cognitive reserve specific effects on aging - normal aging effects on blood flow. - decreased flow in frontal and parietal lobes. - increased flow in cingulate and insular regions - contrasting effects in pathologies like mild cognitive impairment or dementia comparison of active vs. sedentary lifestyles - differences in blood flow patterns study ex - impact of 12 wks of aerobic exercise - reversal of blood flow discrepancy towards left insula - improved working memory and verbal fluency demonstrated by participants neuroprotective effects neuroprotective effects of exercise on endothelial fxn - exercise enhances endothelial function in the central nervous system - increased production of growth factors: - peripherally produced growth factors entering systemic circulation - brain-produced factors improvements in neurotransmitter modulation - enhanced synaptic function and plasticity - improved energy metabolism - promotion of neurogenesis and cell survival additional impact on cognitive focus on executive function, memory, and neuroplasticity - emphasis on brain's executive fxn and memory - + effects of exercise on neuroplasticity additional effects of physical activity - cascade of effects on hormone levels: - serotonin. - melatonin. - dopamine. - impact on mood regulation. - decrease in depressive sx’s demonstrated in multiple studies. impact on brain structure impact on brain structure study by erikson et al. (2010) - randomized controlled study. - participants: 120 pts w/o dementia. - intervention groups: - aerobic exercise 3x a wk at mod intensities - stretching group results: - aerobic group: 1.97 to 2.12% increase in hippocampal volume - stretching group: 1.4% loss in hippocampal volume conclusion: aerobic exercise can reverse 1 to 2% annual hippocampal volume loss attributed to age in healthy adults supporting studies - other studies on progressive resistance training - similar positive results observed overall benefit - promotion of both exercise interventions shown to be beneficial impact at the neuromuscular jxn impact on the peripheral nervous system - focus on the neuromuscular junction. - changes during normal aging: - more mitochondria, deeper postsynaptic junctions, densely located acetylcholine receptors. - aging effects: fewer mitochondria, shallower junctions, fewer activated receptors. effects of physical activity - induces: - increased mitochondrial genesis. - improved mitochondrial function and ATP availability. - increased pre- and post-synaptic activity. - increased # of receptors. summary  3.3 path cognitive changes pathological aging for the CNS : 3 Ds focus on: - depression - delirium - dementia spectrum of dementia - early changes identified as mild cognitive impairment (MCI). - progression towards cognitive diseases possible continued accelerated aging processes. mild cognitive impairment (MCI) - precursor to dementia. - can be: - arrested. - reversed in some individuals presenting MCI. course of cognitive changes w age cognition in older adults normal changes - modest decline in short-term memory. - continued decline in processing speed. - verbal intelligence and personality remain stable. impact of accelerated aging - rapid and steep decline towards mild cognitive impairment (MCI) or cognitive disease. improving cognitive fitness strategies: - physical activity. - nutrition. - engagement in cognitive activities. benefits of cognitive fitness - increases cognitive reserve. - maintains fxn and health. diagnosis of mild cognitive impairment (MCI) - signifies significant loss in cognitive fitness. - potential swift progression to cognitive disease. mild cognitive impairment Definition: “a transitional zone between normal aging and dementia” and is a “symptomatic predementia range of cognition and function... and is not normal” Jekel K et al., 2015 & Albert MS et al., 2011 60 yrs: prevalence is low ^ 1 to 6.7 % rates increases w age to about 25% by age 85 contributors to mild cognitive impairment causes of mild cognitive impairment (MCI) - no single cause; multiple variables involved contributors: - health status - socioeconomic determinants of health - gender or genetic predisposition negative contributors - HTN or vascular pathology - brain infarction - altered lipid metabolism - environment - medication - illness - trauma mitigators - higher level of education - antidepressant therapies - statins DSM-5 diagnostic criteria mild neurocognitive disorder - moderate alcohol consumption practice guideline for MCI - cholinergic therapies - anti-inflammatory agents diagnostic criteria for mild cognitive impairment impact of lifestyle (MCI) by Albert et al. altered by: - concern regarding a change in cognition. - diet - impairment in one or more cognitive domains: - physical activity - memory - executive fxn more practice guidelines for MCI - attention practice guidelines by Peterson et al. - language aim: guidelines for mild cognitive - visual spatial skills impairment (MCI). - preservation of independence in functional recommendation: weaning from abilities (e.g., paying bills, preparing meals). medications contributing to cognitive dx: impairment if possible. - excludes presence of dementia. pharmacological tx types of mild cognitive impairment status: amnestic: - no approved pharmacological tx for - involves memory loss. MCI. non-amnestic: - none shown effective for - primarily involves attention. prevention. clock drawing test benefits of exercise - comparison across stages: types of exercise: - healthy adult - aerobic. - mild cognitive impairment (MCI). - strength training. - late alzheimer's disease. - combined training. observations: studies' findings: in MCI: - prevents declines in cognitive fxn - general structure of the clock present. in individuals w normal fxn - altered spacing of numbers. exercise recommendations for MCI - imprecise or inaccurate hands. frequency: - at least two times a week. duration: - at least 6 months. goal: - prevent further decline towards dementia. effect on training on MCI meta-analysis by Meng et al., 2022 aim: impact of interventions on preventing progression of mild cognitive impairment (MCI) types of Interventions studied - cognitive training - physical therapy - physical activity alone - no training (control group) findings - combined cognitive and physical training: - + effects on global cognition compared to control group - +effects on memory compared to physical activity alone or control - + effects on executive fxn compared to all other groups definition of cognitive training mental exercises to improve cognition: - memory - executive fxn - processing speed. - visual spatial perception also known as: - brain games. - cogniSize. - neurobics. which training? PT and mitigating mild cognitive impairment (MCI) progression - importance of physical activity in managing MCI progression. optimal exercise types systematic review by Huang et al., 2022 -examined efficacy of exercise interventions on cognitive fxn findings: - resistance exercise: - highest probability to slow cognitive decline - particularly beneficial for those with cognitive dysfxn (e.g., dementia) multi-component exercise: - most promising for neuroprotective effects - effective in preventing global cognitive loss and enhancing executive fxn in MCI - combo of any 2 types of exercise: - resistance training - balance training - aerobic training impact on memory resistance training: - higher impact on memory in MCI effectiveness of mind-body exercises - tai Chi, yoga, dance: - not shown to be more beneficial overall compared to multi-component or resistance training progression of MCI impact of physical activity - potential to reverse or halt progression of mild cognitive impairment (MCI) progression of mild cognitive impairment (MCI) - some cases progress to dementia. statistics on progression - 10%-15% of individuals with MCI progress to alzheimer's disease or other dementia per year - 55%-65% eventually progress to some form of dementia types of MCI - amnestic MCI variant: - progresses to dementia at a ratio of 3 to one compared to other variants Summary Mild cognitive impairment presents with decreased cognitive function with intact functional independence Exercise alone has significant impact on slowing cognitive decline  3.4 into to dementia DSM-5 diagnostic criteria: major neurocognitive disorder diagnostic criteria for dementia memory impairment: - difficulty learning new info or recalling previously learned info presence of one or more of: - aphasia (language impairment). - apraxia (inability to execute motor activities). - agnosia (failure to recognize or identify objects despite intact sensory fxn). - disturbance in executive fxn (e.g., planning, organizing). fxn impairment - significant decline in social or occupational fxning delirium and dementia relationship: - not exclusive; can occur concurrently. - overlap can lead to misdx or lack of dx. types of dementia dementia overview - umbrella term for sxs related to cognitive impairment major types of dementia alzheimer's disease: - most common cause vascular Dementia: - second most common lewy body dementia - frontotemporal dementia less common types - prion diseases (e.g., Creutzfeldt-Jakob disease). - neurodegenerative diseases associated w: - parkinson's - chronic traumatic encephalopathy (CTE) vascular dementia definition and epidemiology - second most common type of dementia. - associated w vascular comorbidities: - HTN - atrial fibrillation. - stroke. - diabetes. - smoking. clinical presentation distinguishing features from alzheimer's disease - abrupt and stepwise symptom onset - often associated w minor strokes or small vessel disease - cumulative cognitive decline over time.  affected fxns - memory. - abstract thinking. - judgment. - attention. - complex activities. variable fxnal deterioration - selective based on affected vasculature behavioral changes - altered impulse control - change in personality - emotional ability - depression - apathy vascular dementia: imaging vascular dementia characteristics - affected brain regions - more common in frontal lobes than temporal lobes cognitive performance compared to alzheimer's disease - poorer performance in: - verbal fluency - perseveration - abstract thinking better recall and memory compared to Alzheimer's disease neuroimaging findings - MRI: - detects lacunar infarcts due to chronic reduced blood flow - PET scan interpretation: - red indicates more active areas. - green indicates less active areas. comparison with Alzheimer's Disease on neuroimaging - alzheimer's disease: - increased frontal lobe activity (red). - decreased parietal and temporal lobe activity (green). vascular dementia: - multiple white areas on MRI (indicating lacunar infarcts). - increased parietal and temporal lobe activity (PET scan). - decreased frontal lobe activity (PET scan). vascular dementia: pathophysiology pathogenesis of vascular dementia differentiation from other dementias - related to stroke pathogenesis - combination of modifiable and non-modifiable risk factors & sex race an genetics age , , stroke mechanism - thrombotic or embolic stroke. - blocked blood supply to brain region. - leads to hypoperfusion. cascade of effects - oxidative stress. - endothelial dysfxn - neuronal dysfxn - vascular cognitive impairment modifiable risk factors - importance in reducing stroke risk: - smoking cessation - diet management - physical activity management of comorbidities aimed at preventing: - HTN - diabetes - hyperlipidemia lewy body dementia lewy body dementia (LBD) overview association with parkinsonism - commonly diagnosed alongside PD pathophysiology - cause: - buildup of alpha-synuclein protein (Lewy bodies) inside neuron nuclei result: - neuronal degeneration in cortex or brainstem. genetic links - associated genes: - PARK11 - full life of protein genes distribution of alpha-synuclein - throughout the brain - accumulation in basal ganglia: - leads to dopamine degradation - contributes to neuronal death clinical ex robin williams: - initially diagnosed with PD - later found to have Lewy body dementia (LBD). - tragic outcome: suicide. lewy body dementia clinical presentation motor sx’s of lewy body dementia (LBD) - decreased effective use of dopamine in basal ganglia - parkinsonian motor sx’s: - stiffness - tremor - poor coordination - difficulty walking non-motor sx’s of LBD distribution of lewy bodies - accumulation throughout the brain  associated sx - recurrent visual hallucinations (hallmark sx) - progressive cognitive decline: - fluctuations in alertness and attention - poor executive fxn - mood changes - memory impairment imaging of lewy body imaging techniques for differential diagnosis DAT Scan (dopamine transporter scan) purpose: - assess dopamine uptake in the brain comparison: - normal healthy individual: - brightness in basal ganglia (normal dopamine use) alzheimer's disease: - similar brightness in basal ganglia (normal dopamine use) lewy body dementia: - decreased or altered dopamine processing in basal ganglia MRI Findings comparison: lewy body dementia: - lack of atrophy in medial temporal lobe alzheimer's disease: - atrophy in medial temporal lobe PET Imaging observation: lewy body dementia: - decreased use of occipital lobe (yellow color) - potential correlation with visual hallucinations normal controls: - dark orange color in occipital lobe (normal activity) frontotemporal dementia frontotemporal dementia (FTD) overview association w PD - second most frequent cause of early onset dementia incidence: - 15 to 22 cases per 100,000 bw ages 45 to 65 pathology - neurodegeneration: - in frontal and temporal lobes etiology - unknown etiology - genetic component: - 30 to 50% of cases pathophysiology - neuronal loss - astrocytic gliosis - abnormalities in specific proteins: - tau. - RNA-DNA binding proteins variants of frontotemporal dementia classification of Frontotemporal Dementia (FTD) - 3 main variants: - behavioral variant - non-fluent (primary progressive aphasia) variant - semantic variant behavioral variant characteristics: - disinhibition - socially inappropriate behaviors - apathy - loss of empathy - preserved memory and visual spatial fxn non-fluent (primary progressive aphasia) variant characteristics: - preserved social skills and personalities. - effortful speech. - impaired comprehension semantic variant characteristics: - primary progressive aphasia - circumlocutory speech - impaired word finding - tendency to ramble imaging of frontotemporal dementia comparison of frontotemporal dementia (FTD) and alzheimer's disease brain areas affected FTD: - targets frontal and temporal lobes. alzheimer's disease: - Impacts parietal and temporal lobes. beta amyloid presence - alzheimer's disease: - heightened presence of beta amyloid proteins. - FTD: - beta amyloid proteins less prominent or absent. MRI findings FTD: - lack of volume loss in parietal and temporal lobes. - no cortical atrophy in frontal lobe. PET Scanning: - decreased or green brain activity confined to frontal lobes. Summary Dementia characterizes substantial cognitive impairment with loss of functional independence Types of dementia can be differentiated by neuroanatomical pathophysiology and clinical presentation 1. Alzheimer’s disease 2. Vascular dementia 3. Lewy body dementia 4. Frontotemporal dementia  3.5 Alzheimer’s Disease Most common type of dementia & leading neurodegenerative dx Cause: unknown Risk factors genetics - apolipoprotein E or beta amyloid protein processing genes cellular aging changes w/ DNA - methylation & inflammation impaired microvascular fx head trauma hx of delirium increased prev in females (maybe bc longer lifespan) Pathophysiology presence of amyloid plaques & neurofribillary tangles plaque builds bc cant clear beta amyloid so forms clumps b/w neurons -> neurodegeneration more plaque = worse plaque form before knowing have dx - dont know if causes dx or just outcome tangles = dying/dead neurons tangled w/ Tau protein ↑ red = active green = less active decreased activity in temporal lobe = MCI decreased activity in cerebral cortex = alzheimer’s r amyloid PET can see the plaque buildup alzheimer’s = most common cause of dementia & irreversible progressive neurological decline - refer to chart for what results in Classic Triad visual spatial defects language changes memory impairment Life expectancy window 8-20 yrs  Dx Severity no dx test confirmed post mortem look for biomarkers (amyloid plaque & neuronal death) hx of progressive cognitive decline - interferes w/ work, social, relationships (dif from MCI) Prognosis/Life expectancy varies 8-10 w/ MCI develop alzheimer’s w/in 7 years compared to 1/3 w/ normal cognition dx after 80 = 3-4 years earlier dx = survive 10+ years Alzheimers w/ high spatial cognitive impairment vestibular impairment higher fall risk/wandering older ppl: reduced mental rot, spatial mem, spatial navigation reduced hippocampal volume w/ poor vestib fxn Study degeneration of saccular fxn w/ age - worse w/ auto toxicity / antibiotic use decreases input to hippocampus/prefrontal cortex w/ heightened dysfxn in spatial reasoning compared to alzheimer’s Gait Variability fluctuations/inconsistencies b/w strides. step width, step swing velocity, asymmetries neurodegenerative dx = high gait variability can help differentiate b/w lewy body dementia, MCI, frontotemporal dementia  focus on how differ from each other in neuroanatomy and clinical presentation Summary dominant types of dementia can be distinguished by affected neuroanatomy, cognitive impairment, & motor impairments alzheimer’s dx affects the parieto - temporal lobes & characterized by plaques & tangles 3.6 Assessment of Cognition 1C evidence - not recommending screening assessment of asymptomatic ppl - rapid fxnal screening tools (pfeffer fxnal acitivites questionnaire or disability assessment for dementia but monitor for early sx high evidence - symptomatic ppl - rapid psychometric tools - clock drawing test - Moca - MMSE Know theses 4 screening assessment tools Mini mental status examination Montreal cognitive assessment tool mini COG st. louis university mental status exam (SLUMS) bc of restrictions on MMSE MMSE 11 Q orientation, registration, attn, calculation, recall, language more prone to ceiling affects than MOCA determine competence in clinical decision making max score 30 mild impairment = 18-24 severe = 17 or less MOCA 3 versions bc want to avoid learning 16 Q memory, attn, language, delayed recall, visual spatial, executive skills, naming, abstract thought max = 30 26 or more = norm cog fxn - if less than 12 yrs of edu add a point to balance identify w/ mild cog impairment need certification now!  Mini COG 2 item test assesses word recall clock draw total = 5 points less than 3 = further assessment SLUM 11 items attn, immediate recall, orientation, delayed recall/interference, numeric calculation & registration, memory of immediate recall/ interference, registration/digit span, visual spatial, executive fxn, extrapolation out of 30 consider education level (completed HS) normal, mild neurocognitive disorder, dementia Clock Drawing Test assess visual spatial skills & executive fxn, attn, motor fxn, concentration can be used post stroke for neglect least cog impairment top left, worse as go down Trail Making test connect dots in order executive fxn, visual spatial skills, visual scanning & attn, task switching can do with letters and numbers to make more challenging part of MOCA Summary screening for cog impairment is essential for holistic assessment & evaluation to develop an appropriate plan of care inclusive of aging concerns