cognitive-reserve-cbs-psp

cognitive-reserve-cbs-psp

Introduction

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">cognitive-reserve-cbs-psp</th>
</tr>
<tr>
<td class="label">Stage</td>
<td>Activity</td>
</tr>
<tr>
<td class="label">Early (PSPRS <40)</td>
<td>Group singing + simple percussion + RAS walking</td>
</tr>
<tr>
<td class="label">Mid (PSPRS 40–60)</td>
<td>Individual singing + music listening + chair rhythm</td>
</tr>
<tr>
<td class="label">Late (PSPRS >60)</td>
<td>Receptive music (headphones) + caregiver-led singing</td>
</tr>
<tr>
<td class="label">Day</td>
<td>Morning (30 min)</td>
</tr>
<tr>
<td class="label">Mon</td>
<td>Music therapy (group singing)</td>
</tr>
<tr>
<td class="label">Tue</td>
<td>Physical exercise (stage-adapted)</td>
</tr>
<tr>
<td class="label">Wed</td>
<td>SLP session (voice + narrative)</td>
</tr>
<tr>
<td class="label">Thu</td>
<td>Physical exercise (dual-task)</td>
</tr>
<tr>
<td class="label">Fri</td>
<td>Cognitive stimulation (executive tasks)</td>
</tr>
<tr>
<td class="label">Sat-Sun</td>
<td>Caregiver-led activities, family engagement, rest</td>
</tr>
<tr>
<td class="label">Dimension</td>
<td>Score (0-10)</td>
</tr>
<tr>
<td class="label">Mechanistic Clarity</td>
<td>8</td>
</tr>
<tr>
<td class="label">Clinical Evidence</td>
<td>5</td>
</tr>
<tr>
<td class="label">Preclinical Evidence</td>
<td>4</td>
</tr>
<tr>
<td class="l

cognitive-reserve-cbs-psp

Introduction

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">cognitive-reserve-cbs-psp</th>
</tr>
<tr>
<td class="label">Stage</td>
<td>Activity</td>
</tr>
<tr>
<td class="label">Early (PSPRS <40)</td>
<td>Group singing + simple percussion + RAS walking</td>
</tr>
<tr>
<td class="label">Mid (PSPRS 40–60)</td>
<td>Individual singing + music listening + chair rhythm</td>
</tr>
<tr>
<td class="label">Late (PSPRS >60)</td>
<td>Receptive music (headphones) + caregiver-led singing</td>
</tr>
<tr>
<td class="label">Day</td>
<td>Morning (30 min)</td>
</tr>
<tr>
<td class="label">Mon</td>
<td>Music therapy (group singing)</td>
</tr>
<tr>
<td class="label">Tue</td>
<td>Physical exercise (stage-adapted)</td>
</tr>
<tr>
<td class="label">Wed</td>
<td>SLP session (voice + narrative)</td>
</tr>
<tr>
<td class="label">Thu</td>
<td>Physical exercise (dual-task)</td>
</tr>
<tr>
<td class="label">Fri</td>
<td>Cognitive stimulation (executive tasks)</td>
</tr>
<tr>
<td class="label">Sat-Sun</td>
<td>Caregiver-led activities, family engagement, rest</td>
</tr>
<tr>
<td class="label">Dimension</td>
<td>Score (0-10)</td>
</tr>
<tr>
<td class="label">Mechanistic Clarity</td>
<td>8</td>
</tr>
<tr>
<td class="label">Clinical Evidence</td>
<td>5</td>
</tr>
<tr>
<td class="label">Preclinical Evidence</td>
<td>4</td>
</tr>
<tr>
<td class="label">Replication</td>
<td>5</td>
</tr>
<tr>
<td class="label">Effect Size</td>
<td>4</td>
</tr>
<tr>
<td class="label">Safety/Tolerability</td>
<td>8</td>
</tr>
<tr>
<td class="label">Biological Plausibility</td>
<td>8</td>
</tr>
<tr>
<td class="label">Actionability</td>
<td>9</td>
</tr>
</table>

Cognitive reserve (CR) describes the brain's capacity to maintain function despite accumulating neuropathology, a concept first formalized by Yaakov Stern in his seminal 2002 framework. In [corticobasal syndrome (CBS)](/diseases/corticobasal-syndrome) and [progressive supranuclear palsy (PSP)](/diseases/progressive-supranuclear-palsy), cognitive reserve takes on unique significance because these 4R-[tauopathies](/mechanisms/tau-pathology) attack cortical and subcortical circuits simultaneously, producing distinctive combinations of motor impairment (asymmetric apraxia in CBS, postural instability and vertical gaze palsy in PSP) alongside executive dysfunction, behavioral changes, and language deterioration. Unlike typical [Alzheimer's disease](/diseases/alzheimers-disease), where memory-focused interventions dominate, CBS/PSP cognitive reserve strategies must be adapted around profound motor limitations, apraxia, oculomotor dysfunction, and rapid functional decline.

This page synthesizes the evidence for cognitive reserve-building interventions specifically adapted for CBS and PSP patients, grading activities by disease stage and motor limitation severity, and providing actionable protocols for patients, caregivers, and rehabilitation teams.

Cognitive Reserve Framework

The Stern Model Adapted for Tauopathy

Stern's cognitive reserve model distinguishes between brain reserve (passive, structural — e.g., brain volume, synaptic density) and cognitive reserve (active, functional — e.g., neural efficiency, compensatory recruitment)[@stern2002][@stern2012]. Higher CR correlates with delayed clinical onset despite equivalent pathological burden, as demonstrated in autopsy studies of AD patients with high education levels[@roe2007].

In CBS/PSP, the concept requires adaptation because:

Measuring Cognitive Reserve in CBS/PSP

Standard CR proxies (years of education, occupational complexity, leisure activity participation) show significant associations with clinical outcomes in PSP cohorts. A retrospective analysis of the NNIPPS trial cohort found that higher education was associated with longer time to functional milestones in PSP-Richardson syndrome, independent of baseline disease severity[@rohrer2010]. The Cognitive Reserve Index questionnaire (CRIq) has been validated in atypical parkinsonian disorders and captures three domains — education, working activity, and leisure activities — providing a composite score for clinical use[@nucci2012].

Evidence-Based Interventions

Cognitive Stimulation Therapy (CST)

Cognitive stimulation therapy, originally developed for dementia by Spector and colleagues, involves structured group sessions targeting orientation, word association, categorization, and creative thinking[@spector2003]. While most RCT evidence comes from AD populations, the principles are directly applicable to CBS/PSP with motor adaptations.

Adaptations for CBS/PSP:

• Verbal-dominant activities: Replace manual tasks (puzzles, writing) with verbal equivalents — word games, storytelling, categorization spoken aloud — to accommodate apraxia[@aguirre2013]
• Large-print and audio materials: For PSP patients with vertical gaze palsy and convergence insufficiency, use auditory stimuli, large-print cards at eye level, and voice-activated devices[@boxer2017]
• Shorter sessions (30–45 min): CBS/PSP patients fatigue more rapidly than AD patients due to concurrent motor effort and dysautonomia[@golbe2014]
• Executive function focus: Emphasize planning, sequencing, and set-shifting tasks rather than memory encoding, matching the frontal-predominant deficit profile[@burrell2014]

Music Therapy

Music therapy has strong neurobiological rationale for CBS/PSP: musical processing engages bilateral temporoparietal networks that are relatively spared in frontotemporal-predominant tauopathies, and rhythm processing via the basal ganglia–supplementary motor area circuit can be leveraged for motor rehabilitation[@srkm2008][@thaut2015].

Receptive Music Therapy:

• Passive listening to preferred music activates the default mode network, reduces cortisol, and improves mood in dementia patients — benefits that translate directly to CBS/PSP[@van2018]
• A randomized trial of individualized music listening in 89 dementia patients showed significant reductions in agitation (Cohen-Mansfield Agitation Inventory, p<0.001) and improved emotional well-being over 8 weeks[@raglio2008]

• Rhythmic auditory stimulation (RAS): Metronome-cued walking improves gait velocity and cadence in parkinsonian disorders; applicable to PSP gait freezing[@thaut1996]
• Singing and vocalization: Preserves respiratory function, engages laryngeal motor planning (sparing apraxic limb pathways), and maintains social engagement[@haneishi2001]
• Adapted percussion: For CBS patients with unilateral apraxia, the less-affected hand can engage with simple percussion instruments, maintaining bilateral sensorimotor integration[@altenmller2015]
• Music-based reminiscence: Autobiographical music playlists engage preserved long-term memory circuits and improve behavioral symptoms[@raglio2008]

Art and Creative Therapies

Visual art therapy engages visuospatial and creative networks that may be differentially affected in CBS (parietal) versus PSP (frontal)[@chancellor2014]. Adaptations include:

• CBS: Use the less-affected hand; focus on abstract/expressive art rather than representational drawing; digital art with touchscreen interfaces can accommodate limited fine motor control
• PSP: Position materials at eye level to accommodate downgaze palsy; use large-format canvases; emphasize tactile media (clay, textured collage) over visual precision tasks
• Both: Art appreciation and discussion groups provide cognitive stimulation without motor demands

Physical Exercise as Cognitive Reserve Builder

Physical exercise enhances cognitive reserve through multiple pathways: upregulation of [BDNF](/entities/bdnf), increased hippocampal neurogenesis, improved cerebrovascular function, and reduced neuroinflammation[@cotman2002][@erickson2011]. In PSP, exercise programs must address the primary motor deficits while preserving cognitive benefits.

Stage-Graded Exercise Protocol:

Early Stage (Independent Ambulation)

• Aerobic: Stationary cycling (reduces fall risk vs. treadmill) 20–30 min, 3×/week
• Resistance: Seated resistance bands focusing on postural extensors (counteracting retrocollis in PSP)
• Balance: Tai chi modified for narrowed base of support (evidence from PD trials shows 67% fall reduction)[@li2012]
• Dual-task: Walking while performing verbal fluency tasks (category naming, counting backward)

• Seated aerobic: Arm ergometry, seated marching
• Functional: Sit-to-stand repetitions, weight shifting
• Cognitive-motor: Seated ball passing with verbal tasks
• Gaze exercises: Horizontal and vertical saccade training (PSP-specific) combined with head movements[@phokaewvarangkul2019]

• Passive range of motion with caregiver
• Respiratory exercises (incentive spirometry)
• Seated upper extremity movements to music
• Guided imagery and relaxation techniques

Speech-Language Pathology Integration

Speech-language pathology (SLP) serves dual roles in CBS/PSP: maintaining communication function AND providing cognitive stimulation through language-based exercises[@skeel2001].

• Lee Silverman Voice Treatment (LSVT LOUD): Originally developed for [Parkinson's disease](/diseases/parkinsons-disease), LSVT LOUD improves vocal intensity and articulation; adaptable for PSP dysarthria[@ramig2001]
• Semantic fluency tasks: Category generation exercises (animals, tools, foods) serve as both language therapy and executive function training
• Narrative retelling: Listening to short stories and retelling them exercises working memory, sequencing, and language production
• Augmentative and alternative communication (AAC): For patients losing speech, early introduction of AAC (speech-generating devices, picture boards) maintains social engagement — a critical CR component[@beukelman2007]
• Swallowing exercises: While not directly cognitive, dysphagia management prevents aspiration pneumonia, preserving health status needed for cognitive engagement[@blumin2004]

Social Engagement and Peer Support

Social engagement is one of the strongest predictors of cognitive reserve[@fratiglioni2004]. For CBS/PSP patients, social withdrawal occurs early due to communication difficulties, falls, and stigma.

Strategies to maintain social engagement:

CBS/PSP-Specific Considerations

Apraxia Adaptations (CBS)

Limb apraxia in CBS is the most significant barrier to standard cognitive reserve activities. The alien limb phenomenon, ideomotor apraxia, and cortical sensory loss require systematic adaptation[@defined2003]:

• Unilateral activity design: All manual activities should be executable with one hand
• Voice-first interfaces: Smart home devices, audiobooks, and voice-controlled tablets bypass manual dexterity requirements
• Proprioceptive exercises: Weighted objects and textured materials for the affected limb maintain sensorimotor integration without requiring precise voluntary control
• Mirror therapy: Limited evidence suggests mirror therapy may improve body schema awareness in CBS, with potential cognitive co-benefits[@bai2020]

Oculomotor Adaptations (PSP)

Vertical supranuclear gaze palsy, the hallmark of PSP-Richardson syndrome, profoundly affects reading, screen use, and environmental scanning[@respondek2017]:

• Prism glasses: Fresnel prisms redirect the visual field to compensate for downgaze palsy; enable reading and screen use in mid-stage disease
• Audiobook and podcast programs: Replace visual reading with auditory learning; maintained engagement with complex material builds CR
• Eye-level material placement: All visual materials positioned at primary gaze level (horizontal), avoiding the need for vertical eye movements
• Vestibulo-ocular reflex exploitation: Training patients to use head movements rather than saccades for visual scanning

Behavioral and Apathy Management

Both CBS and PSP produce frontal behavioral changes including apathy, disinhibition, and emotional blunting that undermine motivation for CR activities[@okeeffe2007]:

• Structured scheduling: Fixed daily routines for cognitive activities reduce the executive demand of initiation
• Environmental cueing: Visual/auditory reminders for activity engagement
• Caregiver-facilitated participation: External motivation from a trained caregiver compensates for intrinsic motivational deficits
• Pharmacological adjuncts: Low-dose amantadine or methylphenidate may reduce apathy sufficiently to enable engagement with CR activities, though evidence in PSP/CBS is limited[@litvan1996a]

Implementation Framework

Assessment and Personalization

Weekly Schedule Template

Monitoring and Adjustment

• Monthly: PSP Rating Scale or CBS-specific functional assessment
• Quarterly: Repeat cognitive screening (MoCA, FAB) to track trajectory
• Ongoing: Activity log maintained by caregiver, tracking engagement duration and quality
• Adjustment triggers: Decline in any domain should prompt activity modification, not cessation — the goal is to maintain engagement at an achievable level throughout disease progression

Combination with Pharmacological Approaches

Cognitive reserve interventions should be combined with evidence-based pharmacological approaches where appropriate:

• [Cholinesterase inhibitors](/entities/cholinesterase-inhibitors): [Rivastigmine](/entities/rivastigmine) has modest evidence for cognitive symptoms in PSP; may enhance the substrate for cognitive reserve interventions[@litvan2001]
• [Coenzyme Q10](/therapeutics/coenzyme-q10-neurodegeneration): Mitochondrial support may preserve neuronal viability, extending the window for CR interventions
• [NAD+ precursors](/therapeutics/nad-precursors-neurodegeneration): NMN/NR supplementation supports cellular energy metabolism and sirtuin activation
• [Melatonin](/therapeutics/melatonin-tauopathy): Sleep quality optimization is essential for memory consolidation and CR maintenance
• [Low-dose lithium](/therapeutics/lithium-tauopathy): [GSK-3β](/entities/gsk3-beta) inhibition may reduce tau phosphorylation, potentially slowing the pathological driver

Caregiver Role and Training

Caregivers are the essential enablers of cognitive reserve in CBS/PSP[@schrag2003]. Caregiver training should include:

The REACH II intervention model, adapted for atypical parkinsonism, provides a structured framework for caregiver skill-building that improves both caregiver well-being and patient outcomes[@belle2006].

Limitations and Research Gaps

Future research priorities include multi-site RCTs of adapted cognitive stimulation in PSP (building on the ENGAGE-PSP infrastructure), tau PET-correlated CR studies, and development of CBS/PSP-specific digital cognitive training platforms[@hglinger2017].

Evidence Quality Rubric (CBS/PSP Cognitive Reserve Program)

To align with the CBS/PSP intervention framework used across treatment monographs, this cognitive reserve protocol is scored across 8 dimensions (0-10 each, maximum 80)[@hglinger2017]:

Total: 51/80

Interpretation: cognitive reserve programming is a high-feasibility, moderate-evidence intervention that is best deployed as a foundational layer in multimodal care, not as a stand-alone disease-modifying strategy.

12-Week Stage-Adapted Program (Operational Protocol)

Program Goals

Week 0: Baseline Setup

• Complete baseline profiling: CRIq, PSPRS/CBS functional staging, fall history, dysphagia screen, and caregiver capacity map[@nucci2012][@blumin2004]
• Build an individualized activity stack:
• one music-based activity
• one cognitive-language activity
• one movement activity
• one social connection activity
• Define explicit stop rules and escalation contacts before program start[@respondek2017][@boxer2017]

Weeks 1-4: Stabilization Phase

• Frequency target: 5 intervention days/week, 30-60 minutes/day total (can be split into 2 blocks)
• Priority:
• establish routine predictability (same time, same place)
• maximize early wins to reduce avoidance and apathy
• tune interface choices (audio-first vs visual, one-step vs multi-step prompts)
• Stage adaptation:
• Early stage: dual-task walking + verbal fluency + group singing
• Mid stage: seated cognitive-motor drills + caregiver-facilitated narrative recall
• Late stage: short receptive music blocks + guided conversation + passive/assisted movement

Weeks 5-8: Intensification Phase

• Increase challenge only if adherence is >=70% and fatigue recovery is adequate within 24 hours[@zampieri2006]
• Add one complexity lever at a time:
• longer verbal sequencing chains
• richer social interaction targets
• mild dual-task cognitive load during safe mobility drills
• If progression worsens balance, downgrade motor complexity immediately and preserve cognitive engagement in seated or bed-supported formats[@respondek2017][@phokaewvarangkul2019]

Weeks 9-12: Consolidation Phase

• Shift to sustainability model:
• prioritize highest-yield, best-tolerated activities
• transition ownership to caregiver routine scripts and cueing cards
• lock in tele-support cadence (SLP/PT/OT check-ins)
• Evaluate trajectory against baseline:
• activity minutes/week
• communication participation frequency
• caregiver burden and feasibility
• falls/near-falls and aspiration events[@blumin2004][@schrag2003][@belle2006]

Safety, Contraindications, and Stop Rules

Cognitive reserve interventions are generally low risk, but the CBS/PSP population has high fall, aspiration, and autonomic burden. Safety engineering is therefore mandatory, not optional[@respondek2017][@boxer2017][@blumin2004].

Absolute Stop Triggers (same day clinical escalation)

• New recurrent falls, syncopal episodes, or near-syncope during activity
• New coughing/choking clusters during voice or swallow-linked tasks
• Acute delirium, major behavioral decompensation, or rapidly worsening dysphagia
• New inability to follow previously manageable one-step commands

Relative Stop/Modify Triggers

• Post-session exhaustion >24 hours
• Marked frustration, distress, or agitation that persists after simplification
• Caregiver strain that prevents safe supervision

Risk Controls by Domain

• Mobility block:
• remove all dual-task standing drills if fall risk increases
• substitute seated rhythm or upper-limb-assisted tasks[@thaut1996][@zampieri2006]
• Vision/oculomotor block (PSP):
• avoid downward gaze-dependent work
• maintain eye-level materials and auditory alternatives[@respondek2017][@phokaewvarangkul2019]
• Language/communication block:
• transition early to AAC supports when speech reliability declines[@beukelman2007]
• Nutrition/swallow block:
• coordinate with SLP for texture/sip safety before voice-heavy sessions[@skeel2001][@blumin2004]

Clinical Positioning in a Multimodal CBS/PSP Plan

Cognitive reserve programming should be implemented as a core longitudinal scaffold around which pharmacologic and supportive therapies are layered. In practice, the intervention is most effective when delivered with synchronized caregiver coaching, regular SLP/PT/OT touchpoints, and realistic stage-adjusted goals rather than fixed performance targets[@skeel2001][@schrag2003][@belle2006].

This framing avoids a common failure mode: abandoning cognitive engagement when motor disability increases. In CBS/PSP, the correct response to progression is not intervention withdrawal, but format adaptation (audio-first, seated, shorter-duration, caregiver-mediated) to preserve meaningful cognitive and social participation as long as safely possible[@burrell2014][@respondek2017][@fratiglioni2004].

CBS/PSP Cross-Link Hub

High-Priority Navigation

• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
• [Corticobasal Syndrome](/diseases/corticobasal-syndrome)
• [Corticobasal Degeneration](/diseases/corticobasal-degeneration)
• [4R Tauopathy Mechanism](/mechanisms/4r-tauopathy)
• [Cortisol-Tau Pathway](/mechanisms/cortisol-tau-pathway)
• [Gut-Brain Axis in Tauopathy](/mechanisms/gut-brain-axis-tauopathy)
• [Imaging Biomarkers for CBS/PSP](/biomarkers/cbs-psp-imaging-biomarkers)
• [Tau PET in CBS/PSP](/biomarkers/tau-pet-cbs-psp)
• [MRI Atrophy Patterns in CBS/PSP](/biomarkers/mri-atrophy-cbs-psp)
• [DTI White Matter Changes in CBS/PSP](/biomarkers/dti-white-matter-cbs-psp)
• [CBS/PSP Daily Action Plan](/therapeutics/cbs-psp-daily-action-plan)
• [CBS/PSP Rehabilitation Guide](/therapeutics/cbs-psp-rehabilitation-guide)
• [CBS/PSP Clinical Trials Guide](/therapeutics/cbs-psp-clinical-trials-guide)
• [CBS/PSP Treatment Rankings](/therapeutics/cbs-psp-treatment-rankings)
• [Exercise and Physical Activity for CBS/PSP](/therapeutics/exercise-cbs-psp)
• [Protective Strategies for CBS/PSP](/therapeutics/protective-strategies-cbs-psp)
• [Melatonin for Tauopathy](/therapeutics/melatonin-tauopathy)
• [Low-Dose Lithium for Tauopathy](/therapeutics/lithium-tauopathy)
• [Rapamycin for Tauopathy](/therapeutics/rapamycin-tauopathy)
• [Senolytics for Neurodegeneration](/therapeutics/senolytics-neurodegeneration)
• [TUDCA/UDCA for Neurodegeneration](/therapeutics/tudca-udca-neurodegeneration)
• [Spermidine for Neurodegeneration](/therapeutics/spermidine-neurodegeneration)
• [Photobiomodulation for Neurodegeneration](/therapeutics/photobiomodulation-neurodegeneration)
• [Urolithin A for Neurodegeneration](/therapeutics/urolithin-a-neurodegeneration)
• [Deferiprone for Neurodegeneration](/therapeutics/deferiprone-neurodegeneration)
• [Ambroxol for Neurodegeneration](/therapeutics/ambroxol-neurodegeneration)
• [Omega-3 Fatty Acids for Neurodegeneration](/therapeutics/omega-3-fatty-acids-neurodegeneration)
• [Coenzyme Q10 for Neurodegeneration](/therapeutics/coenzyme-q10-neurodegeneration)
• [Alpha-Lipoic Acid for Neurodegeneration](/therapeutics/alpha-lipoic-acid-neurodegeneration)
• [NAD+ Precursors for Neurodegeneration](/therapeutics/nad-precursors-neurodegeneration)
• [Mitochondrial Support Strategies for CBS/PSP](/therapeutics/mitochondrial-neuroprotection)
• [Autophagy Enhancement for Tauopathy](/therapeutics/autophagy-enhancement-tauopathy)

See Also

• [Cognitive Reserve in Aging](/mechanisms/cognitive-reserve)
• [CBS/PSP Daily Action Plan](/therapeutics/cbs-psp-daily-action-plan)
• [CBS/PSP Rehabilitation Guide](/therapeutics/cbs-psp-rehabilitation-guide)
• [CBS/PSP Treatment Rankings](/therapeutics/cbs-psp-treatment-rankings)
• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) — Biomedical literature database
• [ClinicalTrials.gov](https://clinicaltrials.gov/) — Clinical trial registry
• [CurePSP](https://www.curepsp.org/) — PSP and CBS patient advocacy and research

References

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

• [Aquaporin-4 Polarization Rescue](/hypothesis/h-c8ccbee8) — <span style="color:#81c784;font-weight:600">0.67</span> · Target: AQP4
• [Microglial Purinergic Reprogramming](/hypothesis/h-5daecb6e) — <span style="color:#81c784;font-weight:600">0.66</span> · Target: P2RY12
• [Sphingolipid Metabolism Reprogramming](/hypothesis/h-6657f7cd) — <span style="color:#81c784;font-weight:600">0.61</span> · Target: CERS2
• [Complement C1q Subtype Switching](/hypothesis/h-5a55aabc) — <span style="color:#ffd54f;font-weight:600">0.59</span> · Target: C1QA
• [Glial Glycocalyx Remodeling Therapy](/hypothesis/h-c35493aa) — <span style="color:#ffd54f;font-weight:600">0.58</span> · Target: HSPG2
• [Ephrin-B2/EphB4 Axis Manipulation](/hypothesis/h-e6437136) — <span style="color:#ffd54f;font-weight:600">0.56</span> · Target: EPHB4
• [Netrin-1 Gradient Restoration](/hypothesis/h-05b8894a) — <span style="color:#ffd54f;font-weight:600">0.44</span> · Target: NTN1

Related Analyses:

• [4R-tau strain-specific spreading patterns in PSP vs CBD](/analysis/SDA-2026-04-01-gap-005) &#x1f504;

Pathway Diagram

The following diagram shows the key molecular relationships involving cognitive-reserve-cbs-psp discovered through SciDEX knowledge graph analysis: